Interventional Cardiology & Surgery

Video-based artificial intelligence provided a more accurate and consistent reading of echocardiograms than did experienced sonographers in a blinded trial, a result suggesting that this technology is no longer experimental.

“We are planning to deploy this at Cedars, so this is essentially ready for use,” said David Ouyang, MD, who is affiliated with the Cedars-Sinai Medical School and is an instructor of cardiology at the University of California, both in Los Angeles.

The primary outcome of this trial, called EchoNet-RCT, was the proportion of cases in which cardiologists changed the left ventricular ejection fraction (LVEF) reading by more than 5%. They were blinded to the origin of the reports.

This endpoint was reached in 27.2% of reports generated by sonographers but just 16.8% of reports generated by AI, a mean difference of 10.5% (P < .001).

The AI tested in the trial is called EchoNet-Dynamic. It employs a video-based deep learning algorithm that permits beat-by-beat evaluation of ejection fraction. The specifics of this system were described in a study published 2 years ago in Nature. In that evaluation of the model training set, the absolute error rate was 6% in the more than 10,000 annotated echocardiogram videos.
 

Echo-Net is first blinded AI echo trial

Although AI is already being employed for image evaluation in many areas of medicine, the EchoNet-RCT study “is the first blinded trial of AI in cardiology,” Dr. Ouyang said. Indeed, he noted that no prior study has even been randomized.

After a run-in period, 3,495 echocardiograms were randomizly assigned to be read by AI or by a sonographer. The reports generated by these two approaches were then evaluated by the blinded cardiologists. The sonographers and the cardiologists participating in this study had a mean of 14.1 years and 12.7 years of experience, respectively.

Each reading by both sonographers and AI was based on a single beat, but this presumably was a relative handicap for the potential advantage of AI technology, which is capable of evaluating ejection fraction across multiple cardiac cycles. The evaluation of multiple cycles has been shown previously to improve accuracy, but it is tedious and not commonly performed in routine practice, according to Dr. Ouyang.
 

AI favored for all major endpoints

The superiority of AI was calculated after noninferiority was demonstrated. AI also showed superiority for the secondary safety outcome which involved a test-retest evaluation. Historical AI and sonographer echocardiogram reports were again blindly assessed. Although the retest variability was lower for both (6.29% vs. 7.23%), the difference was still highly significant in favor of AI (P < .001)

The relative efficiency of AI to sonographer assessment was also tested and showed meaningful reductions in work time. While AI eliminates the labor of the sonographer completely (0 vs. a median of 119 seconds, P < .001), it was also associated with a highly significant reduction in median cardiologist time spent on echo evaluation (54 vs. 64 seconds, P < .001).

Assuming that AI is integrated into the routine workflow of a busy center, AI “could be very effective at not only improving the quality of echo reading output but also increasing efficiencies in time and effort spent by sonographers and cardiologists by simplifying otherwise tedious but important tasks,” Dr. Ouyang said.

The trial enrolled a relatively typical population. The median age was 66 years, 57% were male, and comorbidities such as diabetes and chronic kidney disease were common. When AI was compared with sonographer evaluation in groups stratified by these variables as well as by race, image quality, and location of the evaluation (inpatient vs. outpatient), the advantage of AI was consistent.

Cardiologists cannot detect AI-read echos

Identifying potential limitations of this study, James D. Thomas, MD, professor of medicine, Northwestern University, Chicago, pointed out that it was a single-center trial, and he questioned a potential bias from cardiologists able to guess accurately which of the reports they were evaluating were generated by AI.

Dr. Ouyang acknowledged that this study was limited to patients at UCLA, but he pointed out that the training model was developed at Stanford (Calif.) University, so there were two sets of patients involved in testing the machine learning algorithm. He also noted that it was exceptionally large, providing a robust dataset.

As for the bias, this was evaluated as predefined endpoint.

“We asked the cardiologists to tell us [whether] they knew which reports were generated by AI,” Dr. Ouyang said. In 43% of cases, they reported they were not sure. However, when they did express confidence that the report was generated by AI, they were correct in only 32% of the cases and incorrect in 24%. Dr. Ouyang suggested these numbers argue against a substantial role for a bias affecting the trial results.

Dr. Thomas, who has an interest in the role of AI for cardiology, cautioned that there are “technical, privacy, commercial, maintenance, and regulatory barriers” that must be circumvented before AI is widely incorporated into clinical practice, but he praised this blinded trial for advancing the field. Even accounting for any limitations, he clearly shared Dr. Ouyang’s enthusiasm about the future of AI for EF assessment.

Dr. Ouyang reports financial relationships with EchoIQ, Ultromics, and InVision. Dr. Thomas reports financial relationships with Abbott, GE, egnite, EchoIQ, and Caption Health.

Video-based artificial intelligence provided a more accurate and consistent reading of echocardiograms than did experienced sonographers in a blinded trial, a result suggesting that this technology is no longer experimental.

“We are planning to deploy this at Cedars, so this is essentially ready for use,” said David Ouyang, MD, who is affiliated with the Cedars-Sinai Medical School and is an instructor of cardiology at the University of California, both in Los Angeles.

The primary outcome of this trial, called EchoNet-RCT, was the proportion of cases in which cardiologists changed the left ventricular ejection fraction (LVEF) reading by more than 5%. They were blinded to the origin of the reports.

This endpoint was reached in 27.2% of reports generated by sonographers but just 16.8% of reports generated by AI, a mean difference of 10.5% (P < .001).

The AI tested in the trial is called EchoNet-Dynamic. It employs a video-based deep learning algorithm that permits beat-by-beat evaluation of ejection fraction. The specifics of this system were described in a study published 2 years ago in Nature. In that evaluation of the model training set, the absolute error rate was 6% in the more than 10,000 annotated echocardiogram videos.
 

Echo-Net is first blinded AI echo trial

Although AI is already being employed for image evaluation in many areas of medicine, the EchoNet-RCT study “is the first blinded trial of AI in cardiology,” Dr. Ouyang said. Indeed, he noted that no prior study has even been randomized.

After a run-in period, 3,495 echocardiograms were randomizly assigned to be read by AI or by a sonographer. The reports generated by these two approaches were then evaluated by the blinded cardiologists. The sonographers and the cardiologists participating in this study had a mean of 14.1 years and 12.7 years of experience, respectively.

Each reading by both sonographers and AI was based on a single beat, but this presumably was a relative handicap for the potential advantage of AI technology, which is capable of evaluating ejection fraction across multiple cardiac cycles. The evaluation of multiple cycles has been shown previously to improve accuracy, but it is tedious and not commonly performed in routine practice, according to Dr. Ouyang.
 

AI favored for all major endpoints

The superiority of AI was calculated after noninferiority was demonstrated. AI also showed superiority for the secondary safety outcome which involved a test-retest evaluation. Historical AI and sonographer echocardiogram reports were again blindly assessed. Although the retest variability was lower for both (6.29% vs. 7.23%), the difference was still highly significant in favor of AI (P < .001)

The relative efficiency of AI to sonographer assessment was also tested and showed meaningful reductions in work time. While AI eliminates the labor of the sonographer completely (0 vs. a median of 119 seconds, P < .001), it was also associated with a highly significant reduction in median cardiologist time spent on echo evaluation (54 vs. 64 seconds, P < .001).

Assuming that AI is integrated into the routine workflow of a busy center, AI “could be very effective at not only improving the quality of echo reading output but also increasing efficiencies in time and effort spent by sonographers and cardiologists by simplifying otherwise tedious but important tasks,” Dr. Ouyang said.

The trial enrolled a relatively typical population. The median age was 66 years, 57% were male, and comorbidities such as diabetes and chronic kidney disease were common. When AI was compared with sonographer evaluation in groups stratified by these variables as well as by race, image quality, and location of the evaluation (inpatient vs. outpatient), the advantage of AI was consistent.

Cardiologists cannot detect AI-read echos

Identifying potential limitations of this study, James D. Thomas, MD, professor of medicine, Northwestern University, Chicago, pointed out that it was a single-center trial, and he questioned a potential bias from cardiologists able to guess accurately which of the reports they were evaluating were generated by AI.

Dr. Ouyang acknowledged that this study was limited to patients at UCLA, but he pointed out that the training model was developed at Stanford (Calif.) University, so there were two sets of patients involved in testing the machine learning algorithm. He also noted that it was exceptionally large, providing a robust dataset.

As for the bias, this was evaluated as predefined endpoint.

“We asked the cardiologists to tell us [whether] they knew which reports were generated by AI,” Dr. Ouyang said. In 43% of cases, they reported they were not sure. However, when they did express confidence that the report was generated by AI, they were correct in only 32% of the cases and incorrect in 24%. Dr. Ouyang suggested these numbers argue against a substantial role for a bias affecting the trial results.

Dr. Thomas, who has an interest in the role of AI for cardiology, cautioned that there are “technical, privacy, commercial, maintenance, and regulatory barriers” that must be circumvented before AI is widely incorporated into clinical practice, but he praised this blinded trial for advancing the field. Even accounting for any limitations, he clearly shared Dr. Ouyang’s enthusiasm about the future of AI for EF assessment.

Dr. Ouyang reports financial relationships with EchoIQ, Ultromics, and InVision. Dr. Thomas reports financial relationships with Abbott, GE, egnite, EchoIQ, and Caption Health.

Video-based artificial intelligence provided a more accurate and consistent reading of echocardiograms than did experienced sonographers in a blinded trial, a result suggesting that this technology is no longer experimental.

“We are planning to deploy this at Cedars, so this is essentially ready for use,” said David Ouyang, MD, who is affiliated with the Cedars-Sinai Medical School and is an instructor of cardiology at the University of California, both in Los Angeles.

The primary outcome of this trial, called EchoNet-RCT, was the proportion of cases in which cardiologists changed the left ventricular ejection fraction (LVEF) reading by more than 5%. They were blinded to the origin of the reports.

This endpoint was reached in 27.2% of reports generated by sonographers but just 16.8% of reports generated by AI, a mean difference of 10.5% (P < .001).

The AI tested in the trial is called EchoNet-Dynamic. It employs a video-based deep learning algorithm that permits beat-by-beat evaluation of ejection fraction. The specifics of this system were described in a study published 2 years ago in Nature. In that evaluation of the model training set, the absolute error rate was 6% in the more than 10,000 annotated echocardiogram videos.
 

Echo-Net is first blinded AI echo trial

Although AI is already being employed for image evaluation in many areas of medicine, the EchoNet-RCT study “is the first blinded trial of AI in cardiology,” Dr. Ouyang said. Indeed, he noted that no prior study has even been randomized.

After a run-in period, 3,495 echocardiograms were randomizly assigned to be read by AI or by a sonographer. The reports generated by these two approaches were then evaluated by the blinded cardiologists. The sonographers and the cardiologists participating in this study had a mean of 14.1 years and 12.7 years of experience, respectively.

Each reading by both sonographers and AI was based on a single beat, but this presumably was a relative handicap for the potential advantage of AI technology, which is capable of evaluating ejection fraction across multiple cardiac cycles. The evaluation of multiple cycles has been shown previously to improve accuracy, but it is tedious and not commonly performed in routine practice, according to Dr. Ouyang.
 

AI favored for all major endpoints

The superiority of AI was calculated after noninferiority was demonstrated. AI also showed superiority for the secondary safety outcome which involved a test-retest evaluation. Historical AI and sonographer echocardiogram reports were again blindly assessed. Although the retest variability was lower for both (6.29% vs. 7.23%), the difference was still highly significant in favor of AI (P < .001)

The relative efficiency of AI to sonographer assessment was also tested and showed meaningful reductions in work time. While AI eliminates the labor of the sonographer completely (0 vs. a median of 119 seconds, P < .001), it was also associated with a highly significant reduction in median cardiologist time spent on echo evaluation (54 vs. 64 seconds, P < .001).

Assuming that AI is integrated into the routine workflow of a busy center, AI “could be very effective at not only improving the quality of echo reading output but also increasing efficiencies in time and effort spent by sonographers and cardiologists by simplifying otherwise tedious but important tasks,” Dr. Ouyang said.

The trial enrolled a relatively typical population. The median age was 66 years, 57% were male, and comorbidities such as diabetes and chronic kidney disease were common. When AI was compared with sonographer evaluation in groups stratified by these variables as well as by race, image quality, and location of the evaluation (inpatient vs. outpatient), the advantage of AI was consistent.

Cardiologists cannot detect AI-read echos

Identifying potential limitations of this study, James D. Thomas, MD, professor of medicine, Northwestern University, Chicago, pointed out that it was a single-center trial, and he questioned a potential bias from cardiologists able to guess accurately which of the reports they were evaluating were generated by AI.

Dr. Ouyang acknowledged that this study was limited to patients at UCLA, but he pointed out that the training model was developed at Stanford (Calif.) University, so there were two sets of patients involved in testing the machine learning algorithm. He also noted that it was exceptionally large, providing a robust dataset.

As for the bias, this was evaluated as predefined endpoint.

“We asked the cardiologists to tell us [whether] they knew which reports were generated by AI,” Dr. Ouyang said. In 43% of cases, they reported they were not sure. However, when they did express confidence that the report was generated by AI, they were correct in only 32% of the cases and incorrect in 24%. Dr. Ouyang suggested these numbers argue against a substantial role for a bias affecting the trial results.

Dr. Thomas, who has an interest in the role of AI for cardiology, cautioned that there are “technical, privacy, commercial, maintenance, and regulatory barriers” that must be circumvented before AI is widely incorporated into clinical practice, but he praised this blinded trial for advancing the field. Even accounting for any limitations, he clearly shared Dr. Ouyang’s enthusiasm about the future of AI for EF assessment.

Dr. Ouyang reports financial relationships with EchoIQ, Ultromics, and InVision. Dr. Thomas reports financial relationships with Abbott, GE, egnite, EchoIQ, and Caption Health.

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• High-dose furosemide after cardiac surgery is associated with increased mortality and other adverse outcomes.

Why this matters

• The influence of furosemide on prognosis after cardiac surgery is not fully understood.
• The current findings suggest that high-dose furosemide after cardiac surgery is associated with increased risk for death and other adverse events and therefore should be used cautiously in that setting.

Study design

• The retrospective cohort of 6,752 cardiac surgery patients was divided into two groups according to average daily furosemide dosage after cardiac surgery: less than 20 mg (low-dose group, n = 6,033) and at least 20 mg (high-dose group, n = 719).
• The group were compared for total furosemide dose, total furosemide dose of at least 200 mg, total dose of furosemide by patient weight, and average daily furosemide dose of at least 20 mg.
• The primary outcomes were in-hospital mortality and mortality at 1 year after cardiac surgery. Secondary outcomes were length of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours.
• The study excluded patients aged younger than 18 whose weight data was missing or who had more than 5% of their data missing.

Key results

• Patients in the high-dose furosemide group tended to be older and have a higher body mass index (BMI) and higher rates of diabetes, chronic pulmonary diseases, heart failure, renal failure, blood transfusion, vasopressor use, and valvular surgery.
• They also tended have higher white cell counts and higher levels of blood urea nitrogen, creatinine, glucose, and lactate.
• Those in the high-dose group also were on vasopressors and ventilatory support longer.
• In adjusted multivariate analysis, increased in-hospital mortality was associated with average daily furosemide dose, average daily dose of at least 20 mg/d, and total dose of at least 200 mg.
• Increased mortality at 1 year was associated with total furosemide dose and average daily furosemide dose.
• Significant multivariate predictors of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours after cardiac surgery included total furosemide dose, total dose by weight, average daily furosemide dose of at least 20 mg/d, and total dose of at least 200 mg.
• In subgroup analyses, average daily furosemide dose of at least 20 mg/d significantly increased risk for in-hospital mortality among patients younger than 60 years or with BMI of at least 28 who received vasopressors or blood transfusions, those with renal failure, and those with heart failure not involving congestion.

Limitations

• No limitations were discussed.

Disclosures

• The study was supported by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Jiangsu Postdoctoral Science Foundation.
• The authors declared that they have no competing interests.

This is a summary of a preprint research study, “Association between furosemide administration and outcomes in patients undergoing cardiac surgery,” from Jinghang Li, First Affiliated Hospital of Nanjing (China) Medical University, and colleagues on published on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• High-dose furosemide after cardiac surgery is associated with increased mortality and other adverse outcomes.

Why this matters

• The influence of furosemide on prognosis after cardiac surgery is not fully understood.
• The current findings suggest that high-dose furosemide after cardiac surgery is associated with increased risk for death and other adverse events and therefore should be used cautiously in that setting.

Study design

• The retrospective cohort of 6,752 cardiac surgery patients was divided into two groups according to average daily furosemide dosage after cardiac surgery: less than 20 mg (low-dose group, n = 6,033) and at least 20 mg (high-dose group, n = 719).
• The group were compared for total furosemide dose, total furosemide dose of at least 200 mg, total dose of furosemide by patient weight, and average daily furosemide dose of at least 20 mg.
• The primary outcomes were in-hospital mortality and mortality at 1 year after cardiac surgery. Secondary outcomes were length of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours.
• The study excluded patients aged younger than 18 whose weight data was missing or who had more than 5% of their data missing.

Key results

• Patients in the high-dose furosemide group tended to be older and have a higher body mass index (BMI) and higher rates of diabetes, chronic pulmonary diseases, heart failure, renal failure, blood transfusion, vasopressor use, and valvular surgery.
• They also tended have higher white cell counts and higher levels of blood urea nitrogen, creatinine, glucose, and lactate.
• Those in the high-dose group also were on vasopressors and ventilatory support longer.
• In adjusted multivariate analysis, increased in-hospital mortality was associated with average daily furosemide dose, average daily dose of at least 20 mg/d, and total dose of at least 200 mg.
• Increased mortality at 1 year was associated with total furosemide dose and average daily furosemide dose.
• Significant multivariate predictors of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours after cardiac surgery included total furosemide dose, total dose by weight, average daily furosemide dose of at least 20 mg/d, and total dose of at least 200 mg.
• In subgroup analyses, average daily furosemide dose of at least 20 mg/d significantly increased risk for in-hospital mortality among patients younger than 60 years or with BMI of at least 28 who received vasopressors or blood transfusions, those with renal failure, and those with heart failure not involving congestion.

Limitations

• No limitations were discussed.

Disclosures

• The study was supported by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Jiangsu Postdoctoral Science Foundation.
• The authors declared that they have no competing interests.

This is a summary of a preprint research study, “Association between furosemide administration and outcomes in patients undergoing cardiac surgery,” from Jinghang Li, First Affiliated Hospital of Nanjing (China) Medical University, and colleagues on published on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• High-dose furosemide after cardiac surgery is associated with increased mortality and other adverse outcomes.

Why this matters

• The influence of furosemide on prognosis after cardiac surgery is not fully understood.
• The current findings suggest that high-dose furosemide after cardiac surgery is associated with increased risk for death and other adverse events and therefore should be used cautiously in that setting.

Study design

• The retrospective cohort of 6,752 cardiac surgery patients was divided into two groups according to average daily furosemide dosage after cardiac surgery: less than 20 mg (low-dose group, n = 6,033) and at least 20 mg (high-dose group, n = 719).
• The group were compared for total furosemide dose, total furosemide dose of at least 200 mg, total dose of furosemide by patient weight, and average daily furosemide dose of at least 20 mg.
• The primary outcomes were in-hospital mortality and mortality at 1 year after cardiac surgery. Secondary outcomes were length of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours.
• The study excluded patients aged younger than 18 whose weight data was missing or who had more than 5% of their data missing.

Key results

• Patients in the high-dose furosemide group tended to be older and have a higher body mass index (BMI) and higher rates of diabetes, chronic pulmonary diseases, heart failure, renal failure, blood transfusion, vasopressor use, and valvular surgery.
• They also tended have higher white cell counts and higher levels of blood urea nitrogen, creatinine, glucose, and lactate.
• Those in the high-dose group also were on vasopressors and ventilatory support longer.
• In adjusted multivariate analysis, increased in-hospital mortality was associated with average daily furosemide dose, average daily dose of at least 20 mg/d, and total dose of at least 200 mg.
• Increased mortality at 1 year was associated with total furosemide dose and average daily furosemide dose.
• Significant multivariate predictors of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours after cardiac surgery included total furosemide dose, total dose by weight, average daily furosemide dose of at least 20 mg/d, and total dose of at least 200 mg.
• In subgroup analyses, average daily furosemide dose of at least 20 mg/d significantly increased risk for in-hospital mortality among patients younger than 60 years or with BMI of at least 28 who received vasopressors or blood transfusions, those with renal failure, and those with heart failure not involving congestion.

Limitations

• No limitations were discussed.

Disclosures

• The study was supported by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Jiangsu Postdoctoral Science Foundation.
• The authors declared that they have no competing interests.

This is a summary of a preprint research study, “Association between furosemide administration and outcomes in patients undergoing cardiac surgery,” from Jinghang Li, First Affiliated Hospital of Nanjing (China) Medical University, and colleagues on published on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com. A version of this article first appeared on Medscape.com.

A multibiomarker risk score helps predict increased risk for future cardiovascular (CV) events as well as high-risk anatomy at revascularization in stable patients with atherosclerotic cardiovascular disease (ASCVD), a FOURIER trial analysis suggests.

The risk score incorporates high-sensitivity C-reactive protein (hsCRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), and growth differentiation factor 15 (GDF-15).

These routine biomarkers of inflammation and fibrosis, ventricular strain, and myocardial injury are individually associated with incident CV in stable ASCVD and were shown in earlier work to be a multimarker score to predict CV events in patients stabilized after an acute coronary syndrome in the IMPROVE-IT trial.

Validating the score, however, wasn’t really the intent here, explained senior author Brian Bergmark, MD, with the TIMI Study Group, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston.

“We know broadly speaking people with high troponin, BNP, et cetera, are going to have broadly defined clinical events like MIs [myocardial infarctions], death. And we also know on a granular level at a single time point that people who, for example, get a coronary CT scan and have a contemporary troponin level tend to have a little bit more coronary disease,” he said.

“But that leaves this broad swath of, what if we follow people over time? Can biomarkers in some form actually predict specific coronary anatomical characteristics and revascularization procedures in conjunction with clinical events?” Dr. Bergmark continued. “That’s sort of an untouched link or translational step between some of the granular data and these clinical events.”

As published in the Journal of the American College of Cardiology, the post hoc study analyzed baseline blood samples from 21,644 FOURIER participants and adapted the previously studied multimarker score to use hsTnI in place of high-sensitivity troponin T (hsTnT). One point was assigned for each elevated biomarker: hsCRP ≥ 2 mg/L, NT-proBNP ≥ 450 pg/mL, hsTnI ≥ 6 ng/L, and GDF-15 ≥ 1,800 pg/mL.

A total of 6,444 patients had a low score (0 points), 12,439 an intermediate score (1-2 points), and 2,761 a high score (3-4 points). Patients with higher biomarker scores were older and were more likely to have hypertension, diabetes, multiple prior MIs, heart failure, prior coronary artery bypass grafting (CABG), and peripheral artery disease but were less likely to have prior percutaneous coronary intervention (PCI).

Results showed a stepwise increase in 3-year risk for major coronary events (coronary death, MI, or coronary revascularization) from 7.3% with a low score to 11.3% with an intermediate score and 21.0% with a high score. A near tripling of risk remained in those with a high score after adjustment (hazard ratio, 2.90).

Individuals with a high score had twice the risk for any coronary revascularization (HR, 2.10) and complex revascularization (HR, 2.07), as well as increased risks for complex PCI (HR, 1.80), CABG (HR, 2.57), and in-stent restenosis (ISR) revascularization (HR, 1.78).

The study is the first to show an association of these biomarkers with future ISR revascularization in a broad cohort of patients with stable ASCVD, the investigators observe.

It could be a random signal, but “it’s one piece of data as people start to look at other datasets, as we start to understand who’s at risk for ISR, as we understand this disease entity that’s really a pandemic at this point,” Dr. Bergmark said, “I think this is one piece of the puzzle that’s novel.”

Compared with those with a low score, patients with a high biomarker score had significantly higher risks for left main disease greater than 50% (HR, 2.22; P = .003), multivessel disease (HR, 1.99; P < .001), and chronic total occlusion (HR, 2.50; P < .001) at the time of revascularization.

There was no significant interaction between the biomarker score and the effect of evolocumab used in the trial; however, the assessment had limited statistical power, the authors note.

Dr. Bergmark said that the results can inform trial design to select a population at risk for specific types of events and when trying to risk adjust in a population for reimbursement purposes to understand quality metrics, for example, for people coming back with ISR.

“I think refining risk estimates has broad applicability clinically and academically,” he added. “This is one step, with one dataset, pushing these typically broad clinical endpoints to be more specific.”

In an related editorial, Giles Montalescot, MD, PhD, Pitié-Salpêtrière Hospital, Paris, and colleagues write, “Not only does this study validate the multibiomarker score in a new cohort of patients and with new coronary-focused outcomes, but it also opens novel and interesting avenues, on a global approach of cardiovascular risk.”

Possibilities include using this or another multibiomarker risk score to streamline enrichment or selection criteria for a trial or as a surrogate endpoint in proof-of-concept trials to test a new drug aimed at reducing CV risk.

“Beyond clinical research, we could imagine in the future to base our therapeutic decisions on such a score, just like we decide anticoagulation in patients with atrial fibrillation according to the CHA₂DS₂-VASc score,” the editorialists say.

This being said, Dr. Montalescot and colleagues point out that the current multibiomarker risk score assigned equal prognostic value to each of the components, whereas IMPROVE-IT and FOURIER both showed that elevated hsTnT and NT-proBNP were associated with much higher hazard ratios than hsCRP and GDF-15.

Other limitations, they say, are that the categorical nature of the variables, albeit user friendly, prevent any subtle analysis; the score does not include biological risk factors; and questions remain about the impact of the lipid-lowering intervention across risk categories.

FOURIER was funded by Amgen. The TIMI Study Group has received institutional grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr. Bergmark reports grant support from Pfizer, Ionis, AstraZeneca, and Abbott Vascular; and consulting fees from Philips, Abbott Vascular, Servier, Daiichi-Sankyo, Janssen, and Quark Pharmaceuticals. Dr. Montalescot reports research grants to his institution or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cell Prothera, CSL Behring, Europa, Idorsia, IRIS-Servier, Medtronic, MSD, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.

A version of this article first appeared on Medscape.com.

A multibiomarker risk score helps predict increased risk for future cardiovascular (CV) events as well as high-risk anatomy at revascularization in stable patients with atherosclerotic cardiovascular disease (ASCVD), a FOURIER trial analysis suggests.

The risk score incorporates high-sensitivity C-reactive protein (hsCRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), and growth differentiation factor 15 (GDF-15).

These routine biomarkers of inflammation and fibrosis, ventricular strain, and myocardial injury are individually associated with incident CV in stable ASCVD and were shown in earlier work to be a multimarker score to predict CV events in patients stabilized after an acute coronary syndrome in the IMPROVE-IT trial.

Validating the score, however, wasn’t really the intent here, explained senior author Brian Bergmark, MD, with the TIMI Study Group, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston.

“We know broadly speaking people with high troponin, BNP, et cetera, are going to have broadly defined clinical events like MIs [myocardial infarctions], death. And we also know on a granular level at a single time point that people who, for example, get a coronary CT scan and have a contemporary troponin level tend to have a little bit more coronary disease,” he said.

“But that leaves this broad swath of, what if we follow people over time? Can biomarkers in some form actually predict specific coronary anatomical characteristics and revascularization procedures in conjunction with clinical events?” Dr. Bergmark continued. “That’s sort of an untouched link or translational step between some of the granular data and these clinical events.”

As published in the Journal of the American College of Cardiology, the post hoc study analyzed baseline blood samples from 21,644 FOURIER participants and adapted the previously studied multimarker score to use hsTnI in place of high-sensitivity troponin T (hsTnT). One point was assigned for each elevated biomarker: hsCRP ≥ 2 mg/L, NT-proBNP ≥ 450 pg/mL, hsTnI ≥ 6 ng/L, and GDF-15 ≥ 1,800 pg/mL.

A total of 6,444 patients had a low score (0 points), 12,439 an intermediate score (1-2 points), and 2,761 a high score (3-4 points). Patients with higher biomarker scores were older and were more likely to have hypertension, diabetes, multiple prior MIs, heart failure, prior coronary artery bypass grafting (CABG), and peripheral artery disease but were less likely to have prior percutaneous coronary intervention (PCI).

Results showed a stepwise increase in 3-year risk for major coronary events (coronary death, MI, or coronary revascularization) from 7.3% with a low score to 11.3% with an intermediate score and 21.0% with a high score. A near tripling of risk remained in those with a high score after adjustment (hazard ratio, 2.90).

Individuals with a high score had twice the risk for any coronary revascularization (HR, 2.10) and complex revascularization (HR, 2.07), as well as increased risks for complex PCI (HR, 1.80), CABG (HR, 2.57), and in-stent restenosis (ISR) revascularization (HR, 1.78).

The study is the first to show an association of these biomarkers with future ISR revascularization in a broad cohort of patients with stable ASCVD, the investigators observe.

It could be a random signal, but “it’s one piece of data as people start to look at other datasets, as we start to understand who’s at risk for ISR, as we understand this disease entity that’s really a pandemic at this point,” Dr. Bergmark said, “I think this is one piece of the puzzle that’s novel.”

Compared with those with a low score, patients with a high biomarker score had significantly higher risks for left main disease greater than 50% (HR, 2.22; P = .003), multivessel disease (HR, 1.99; P < .001), and chronic total occlusion (HR, 2.50; P < .001) at the time of revascularization.

There was no significant interaction between the biomarker score and the effect of evolocumab used in the trial; however, the assessment had limited statistical power, the authors note.

Dr. Bergmark said that the results can inform trial design to select a population at risk for specific types of events and when trying to risk adjust in a population for reimbursement purposes to understand quality metrics, for example, for people coming back with ISR.

“I think refining risk estimates has broad applicability clinically and academically,” he added. “This is one step, with one dataset, pushing these typically broad clinical endpoints to be more specific.”

In an related editorial, Giles Montalescot, MD, PhD, Pitié-Salpêtrière Hospital, Paris, and colleagues write, “Not only does this study validate the multibiomarker score in a new cohort of patients and with new coronary-focused outcomes, but it also opens novel and interesting avenues, on a global approach of cardiovascular risk.”

Possibilities include using this or another multibiomarker risk score to streamline enrichment or selection criteria for a trial or as a surrogate endpoint in proof-of-concept trials to test a new drug aimed at reducing CV risk.

“Beyond clinical research, we could imagine in the future to base our therapeutic decisions on such a score, just like we decide anticoagulation in patients with atrial fibrillation according to the CHA₂DS₂-VASc score,” the editorialists say.

This being said, Dr. Montalescot and colleagues point out that the current multibiomarker risk score assigned equal prognostic value to each of the components, whereas IMPROVE-IT and FOURIER both showed that elevated hsTnT and NT-proBNP were associated with much higher hazard ratios than hsCRP and GDF-15.

Other limitations, they say, are that the categorical nature of the variables, albeit user friendly, prevent any subtle analysis; the score does not include biological risk factors; and questions remain about the impact of the lipid-lowering intervention across risk categories.

FOURIER was funded by Amgen. The TIMI Study Group has received institutional grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr. Bergmark reports grant support from Pfizer, Ionis, AstraZeneca, and Abbott Vascular; and consulting fees from Philips, Abbott Vascular, Servier, Daiichi-Sankyo, Janssen, and Quark Pharmaceuticals. Dr. Montalescot reports research grants to his institution or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cell Prothera, CSL Behring, Europa, Idorsia, IRIS-Servier, Medtronic, MSD, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.

A version of this article first appeared on Medscape.com.

A multibiomarker risk score helps predict increased risk for future cardiovascular (CV) events as well as high-risk anatomy at revascularization in stable patients with atherosclerotic cardiovascular disease (ASCVD), a FOURIER trial analysis suggests.

The risk score incorporates high-sensitivity C-reactive protein (hsCRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), and growth differentiation factor 15 (GDF-15).

These routine biomarkers of inflammation and fibrosis, ventricular strain, and myocardial injury are individually associated with incident CV in stable ASCVD and were shown in earlier work to be a multimarker score to predict CV events in patients stabilized after an acute coronary syndrome in the IMPROVE-IT trial.

Validating the score, however, wasn’t really the intent here, explained senior author Brian Bergmark, MD, with the TIMI Study Group, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston.

“We know broadly speaking people with high troponin, BNP, et cetera, are going to have broadly defined clinical events like MIs [myocardial infarctions], death. And we also know on a granular level at a single time point that people who, for example, get a coronary CT scan and have a contemporary troponin level tend to have a little bit more coronary disease,” he said.

“But that leaves this broad swath of, what if we follow people over time? Can biomarkers in some form actually predict specific coronary anatomical characteristics and revascularization procedures in conjunction with clinical events?” Dr. Bergmark continued. “That’s sort of an untouched link or translational step between some of the granular data and these clinical events.”

As published in the Journal of the American College of Cardiology, the post hoc study analyzed baseline blood samples from 21,644 FOURIER participants and adapted the previously studied multimarker score to use hsTnI in place of high-sensitivity troponin T (hsTnT). One point was assigned for each elevated biomarker: hsCRP ≥ 2 mg/L, NT-proBNP ≥ 450 pg/mL, hsTnI ≥ 6 ng/L, and GDF-15 ≥ 1,800 pg/mL.

A total of 6,444 patients had a low score (0 points), 12,439 an intermediate score (1-2 points), and 2,761 a high score (3-4 points). Patients with higher biomarker scores were older and were more likely to have hypertension, diabetes, multiple prior MIs, heart failure, prior coronary artery bypass grafting (CABG), and peripheral artery disease but were less likely to have prior percutaneous coronary intervention (PCI).

Results showed a stepwise increase in 3-year risk for major coronary events (coronary death, MI, or coronary revascularization) from 7.3% with a low score to 11.3% with an intermediate score and 21.0% with a high score. A near tripling of risk remained in those with a high score after adjustment (hazard ratio, 2.90).

Individuals with a high score had twice the risk for any coronary revascularization (HR, 2.10) and complex revascularization (HR, 2.07), as well as increased risks for complex PCI (HR, 1.80), CABG (HR, 2.57), and in-stent restenosis (ISR) revascularization (HR, 1.78).

The study is the first to show an association of these biomarkers with future ISR revascularization in a broad cohort of patients with stable ASCVD, the investigators observe.

It could be a random signal, but “it’s one piece of data as people start to look at other datasets, as we start to understand who’s at risk for ISR, as we understand this disease entity that’s really a pandemic at this point,” Dr. Bergmark said, “I think this is one piece of the puzzle that’s novel.”

Compared with those with a low score, patients with a high biomarker score had significantly higher risks for left main disease greater than 50% (HR, 2.22; P = .003), multivessel disease (HR, 1.99; P < .001), and chronic total occlusion (HR, 2.50; P < .001) at the time of revascularization.

There was no significant interaction between the biomarker score and the effect of evolocumab used in the trial; however, the assessment had limited statistical power, the authors note.

Dr. Bergmark said that the results can inform trial design to select a population at risk for specific types of events and when trying to risk adjust in a population for reimbursement purposes to understand quality metrics, for example, for people coming back with ISR.

“I think refining risk estimates has broad applicability clinically and academically,” he added. “This is one step, with one dataset, pushing these typically broad clinical endpoints to be more specific.”

In an related editorial, Giles Montalescot, MD, PhD, Pitié-Salpêtrière Hospital, Paris, and colleagues write, “Not only does this study validate the multibiomarker score in a new cohort of patients and with new coronary-focused outcomes, but it also opens novel and interesting avenues, on a global approach of cardiovascular risk.”

Possibilities include using this or another multibiomarker risk score to streamline enrichment or selection criteria for a trial or as a surrogate endpoint in proof-of-concept trials to test a new drug aimed at reducing CV risk.

“Beyond clinical research, we could imagine in the future to base our therapeutic decisions on such a score, just like we decide anticoagulation in patients with atrial fibrillation according to the CHA₂DS₂-VASc score,” the editorialists say.

This being said, Dr. Montalescot and colleagues point out that the current multibiomarker risk score assigned equal prognostic value to each of the components, whereas IMPROVE-IT and FOURIER both showed that elevated hsTnT and NT-proBNP were associated with much higher hazard ratios than hsCRP and GDF-15.

Other limitations, they say, are that the categorical nature of the variables, albeit user friendly, prevent any subtle analysis; the score does not include biological risk factors; and questions remain about the impact of the lipid-lowering intervention across risk categories.

FOURIER was funded by Amgen. The TIMI Study Group has received institutional grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr. Bergmark reports grant support from Pfizer, Ionis, AstraZeneca, and Abbott Vascular; and consulting fees from Philips, Abbott Vascular, Servier, Daiichi-Sankyo, Janssen, and Quark Pharmaceuticals. Dr. Montalescot reports research grants to his institution or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cell Prothera, CSL Behring, Europa, Idorsia, IRIS-Servier, Medtronic, MSD, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.

A version of this article first appeared on Medscape.com.

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

A version of this article first appeared on Medscape.com.

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

A version of this article first appeared on Medscape.com.

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

A version of this article first appeared on Medscape.com.

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The strongest evidence yet to support clinical guidelines that recommend that people at high risk of endocarditis, such as those who’ve had previous episode the disease or who have a prosthetic cardiac valve, should take antibiotics before they have a tooth pulled or other types of oral surgery, comes from a new study that used two methodologies.

But it also pointed out that two-thirds of the time they aren’t getting that type of antibiotic coverage.

RobertoDavid/iStock/Getty Images Plus

The researchers conducted a cohort study of almost 8 million retirees with employer-paid Medicare supplemental prescription benefits and dental benefits, then conducted a case-crossover study of 3,774 people from the cohort who’d been hospitalized with infectious endocarditis (IE) and who had invasive dental procedures. The bottom line is that the study supports the clinical guidelines from the American Heart Association and the European Society of Cardiology that recommend antibiotic prophylaxis (AP) before dental procedures for patients at high-risk of IE.

Likewise, lead author Martin Thornhill, MBBS, BDS, PhD, said in an interview, the findings also suggest that existing guidelines in the United Kingdom, which recommend against AP in these patients, “should be reconsidered.”

Those AHA and ESC guidelines, however,  are “based on no good quality evidence,” said Dr. Thornhill, professor of translational research in dentistry at the University of Sheffield (England) School of Clinical Dentistry. “Other studies have looked at this, but we’ve done the largest study that has shown the clear association between invasive dental procedures and subsequent development of infective endocarditis.”

In the entire cohort of 7.95 million patients, 3,774 had cases of IE that required hospitalization. The study defined highest risk of IE as meeting one of these six criteria: a previous case of IE; a prosthetic cardiac valve or a valve repair that used prosthetic material; cyanotic congenital heart disease; palliative shunts or conduits to treat CHD; or a congenital heart defect that had been fully repaired, either by  surgery or a transcatheter procedure, with prosthetic material or device – the latter within 6 months of the procedure.

Moderate IE risk included patients who had rheumatic heart disease, nonrheumatic valve disease or congenital valve anomalies—including mitral valve prolapse or aortic stenosis—or hypertrophic cardiomyopathy.

 

Risk classification and poor compliance

Highest-risk patients had significantly higher rates of IE a month after a dental procedure than lower-risk groups:  467.6 cases per 1 million procedures vs. 24.2 for moderate risk and 3.8 for low or unknown risk. A subanalysis found that the odds of IE were significantly increased for two specific dental procedures: extractions, with an odds ratio of 9.22 (95% confidence interval [CI], 5.54-15.88; P < .0001); and other oral surgical procedures, with an OR of 20.18 (95% CI, 11.22-37.74; P < .0001).

The study also found that 32.6% of the high-risk patients undergoing dental procedures got AP. “Clearly that shows a low level of compliance with the guidelines in the U.S.,” Dr. Thornhill said. “That’s something that needs to be addressed.”

The study was unique in that it used both a population cohort study and the case-crossover study. “It didn’t matter which of the two methods we used; we essentially came to the same result, which I think adds further weight to the findings,” Dr. Thornhill said.

This may be the best evidence to support the guidelines that clinicians may get. While the observational nature of this study has its limitations, conducting a randomized clinical trial to further validate the findings would be “logistically impossible,” he said, in that it would require an “absolutely enormous” cohort and coordination between medical and dental databases covering thousands of lives. An RCT would also require not using AP for some patients. “It’s not ethical to keep somebody off of antibiotic prophylaxis when there’s such a high risk of death and severe outcomes,” Dr. Thornhill said.

Ann Bolger, MD, emeritus professor of medicine at the University of California, San Francisco, and coauthor of an editorial comment on the study, said in an interview that this study is noteworthy not only for its dual methodology, but for the quality of the data that matched patients at high risk for IE with prescription and dental records. “The fact that they were able to have those details in enough granularity that they knew whether a dental procedure was likely to meet the criteria for these more invasive exposures really broke it open from my perspective,” she said.

She called the low compliance rate with AHA guidelines “one of the most sobering points of this,” and said it should put clinicians on notice that they must do more to educate and engage with high-risk patients. “The lines of communication here are somewhat fraught; it’s a little bit of a hot potato,” she said. “It’s a really great communications opportunity to get the provider’s attention back on this. You’re a cardiologist; you have to have this conversation when you see your patient with a prosthetic valve or who’s had endocarditis every time they come in. There’s a whole litany, and it takes 3 minutes, but you have to do it.”

The study received funding from Delta Dental of Michigan Research Committee and Renaissance Health Service Corp., and Dr. Thornhill received support from Delta Dental Research and Data Institute for the study. Dr. Bolger participated in the 2007 and 2021 AHA statements on AP to prevent IE.

The strongest evidence yet to support clinical guidelines that recommend that people at high risk of endocarditis, such as those who’ve had previous episode the disease or who have a prosthetic cardiac valve, should take antibiotics before they have a tooth pulled or other types of oral surgery, comes from a new study that used two methodologies.

But it also pointed out that two-thirds of the time they aren’t getting that type of antibiotic coverage.

RobertoDavid/iStock/Getty Images Plus

The researchers conducted a cohort study of almost 8 million retirees with employer-paid Medicare supplemental prescription benefits and dental benefits, then conducted a case-crossover study of 3,774 people from the cohort who’d been hospitalized with infectious endocarditis (IE) and who had invasive dental procedures. The bottom line is that the study supports the clinical guidelines from the American Heart Association and the European Society of Cardiology that recommend antibiotic prophylaxis (AP) before dental procedures for patients at high-risk of IE.

Likewise, lead author Martin Thornhill, MBBS, BDS, PhD, said in an interview, the findings also suggest that existing guidelines in the United Kingdom, which recommend against AP in these patients, “should be reconsidered.”

Those AHA and ESC guidelines, however,  are “based on no good quality evidence,” said Dr. Thornhill, professor of translational research in dentistry at the University of Sheffield (England) School of Clinical Dentistry. “Other studies have looked at this, but we’ve done the largest study that has shown the clear association between invasive dental procedures and subsequent development of infective endocarditis.”

In the entire cohort of 7.95 million patients, 3,774 had cases of IE that required hospitalization. The study defined highest risk of IE as meeting one of these six criteria: a previous case of IE; a prosthetic cardiac valve or a valve repair that used prosthetic material; cyanotic congenital heart disease; palliative shunts or conduits to treat CHD; or a congenital heart defect that had been fully repaired, either by  surgery or a transcatheter procedure, with prosthetic material or device – the latter within 6 months of the procedure.

Moderate IE risk included patients who had rheumatic heart disease, nonrheumatic valve disease or congenital valve anomalies—including mitral valve prolapse or aortic stenosis—or hypertrophic cardiomyopathy.

 

Risk classification and poor compliance

Highest-risk patients had significantly higher rates of IE a month after a dental procedure than lower-risk groups:  467.6 cases per 1 million procedures vs. 24.2 for moderate risk and 3.8 for low or unknown risk. A subanalysis found that the odds of IE were significantly increased for two specific dental procedures: extractions, with an odds ratio of 9.22 (95% confidence interval [CI], 5.54-15.88; P < .0001); and other oral surgical procedures, with an OR of 20.18 (95% CI, 11.22-37.74; P < .0001).

The study also found that 32.6% of the high-risk patients undergoing dental procedures got AP. “Clearly that shows a low level of compliance with the guidelines in the U.S.,” Dr. Thornhill said. “That’s something that needs to be addressed.”

The study was unique in that it used both a population cohort study and the case-crossover study. “It didn’t matter which of the two methods we used; we essentially came to the same result, which I think adds further weight to the findings,” Dr. Thornhill said.

This may be the best evidence to support the guidelines that clinicians may get. While the observational nature of this study has its limitations, conducting a randomized clinical trial to further validate the findings would be “logistically impossible,” he said, in that it would require an “absolutely enormous” cohort and coordination between medical and dental databases covering thousands of lives. An RCT would also require not using AP for some patients. “It’s not ethical to keep somebody off of antibiotic prophylaxis when there’s such a high risk of death and severe outcomes,” Dr. Thornhill said.

Ann Bolger, MD, emeritus professor of medicine at the University of California, San Francisco, and coauthor of an editorial comment on the study, said in an interview that this study is noteworthy not only for its dual methodology, but for the quality of the data that matched patients at high risk for IE with prescription and dental records. “The fact that they were able to have those details in enough granularity that they knew whether a dental procedure was likely to meet the criteria for these more invasive exposures really broke it open from my perspective,” she said.

She called the low compliance rate with AHA guidelines “one of the most sobering points of this,” and said it should put clinicians on notice that they must do more to educate and engage with high-risk patients. “The lines of communication here are somewhat fraught; it’s a little bit of a hot potato,” she said. “It’s a really great communications opportunity to get the provider’s attention back on this. You’re a cardiologist; you have to have this conversation when you see your patient with a prosthetic valve or who’s had endocarditis every time they come in. There’s a whole litany, and it takes 3 minutes, but you have to do it.”

The study received funding from Delta Dental of Michigan Research Committee and Renaissance Health Service Corp., and Dr. Thornhill received support from Delta Dental Research and Data Institute for the study. Dr. Bolger participated in the 2007 and 2021 AHA statements on AP to prevent IE.

The strongest evidence yet to support clinical guidelines that recommend that people at high risk of endocarditis, such as those who’ve had previous episode the disease or who have a prosthetic cardiac valve, should take antibiotics before they have a tooth pulled or other types of oral surgery, comes from a new study that used two methodologies.

But it also pointed out that two-thirds of the time they aren’t getting that type of antibiotic coverage.

RobertoDavid/iStock/Getty Images Plus

The researchers conducted a cohort study of almost 8 million retirees with employer-paid Medicare supplemental prescription benefits and dental benefits, then conducted a case-crossover study of 3,774 people from the cohort who’d been hospitalized with infectious endocarditis (IE) and who had invasive dental procedures. The bottom line is that the study supports the clinical guidelines from the American Heart Association and the European Society of Cardiology that recommend antibiotic prophylaxis (AP) before dental procedures for patients at high-risk of IE.

Likewise, lead author Martin Thornhill, MBBS, BDS, PhD, said in an interview, the findings also suggest that existing guidelines in the United Kingdom, which recommend against AP in these patients, “should be reconsidered.”

Those AHA and ESC guidelines, however,  are “based on no good quality evidence,” said Dr. Thornhill, professor of translational research in dentistry at the University of Sheffield (England) School of Clinical Dentistry. “Other studies have looked at this, but we’ve done the largest study that has shown the clear association between invasive dental procedures and subsequent development of infective endocarditis.”

In the entire cohort of 7.95 million patients, 3,774 had cases of IE that required hospitalization. The study defined highest risk of IE as meeting one of these six criteria: a previous case of IE; a prosthetic cardiac valve or a valve repair that used prosthetic material; cyanotic congenital heart disease; palliative shunts or conduits to treat CHD; or a congenital heart defect that had been fully repaired, either by  surgery or a transcatheter procedure, with prosthetic material or device – the latter within 6 months of the procedure.

Moderate IE risk included patients who had rheumatic heart disease, nonrheumatic valve disease or congenital valve anomalies—including mitral valve prolapse or aortic stenosis—or hypertrophic cardiomyopathy.

 

Risk classification and poor compliance

Highest-risk patients had significantly higher rates of IE a month after a dental procedure than lower-risk groups:  467.6 cases per 1 million procedures vs. 24.2 for moderate risk and 3.8 for low or unknown risk. A subanalysis found that the odds of IE were significantly increased for two specific dental procedures: extractions, with an odds ratio of 9.22 (95% confidence interval [CI], 5.54-15.88; P < .0001); and other oral surgical procedures, with an OR of 20.18 (95% CI, 11.22-37.74; P < .0001).

The study also found that 32.6% of the high-risk patients undergoing dental procedures got AP. “Clearly that shows a low level of compliance with the guidelines in the U.S.,” Dr. Thornhill said. “That’s something that needs to be addressed.”

The study was unique in that it used both a population cohort study and the case-crossover study. “It didn’t matter which of the two methods we used; we essentially came to the same result, which I think adds further weight to the findings,” Dr. Thornhill said.

This may be the best evidence to support the guidelines that clinicians may get. While the observational nature of this study has its limitations, conducting a randomized clinical trial to further validate the findings would be “logistically impossible,” he said, in that it would require an “absolutely enormous” cohort and coordination between medical and dental databases covering thousands of lives. An RCT would also require not using AP for some patients. “It’s not ethical to keep somebody off of antibiotic prophylaxis when there’s such a high risk of death and severe outcomes,” Dr. Thornhill said.

Ann Bolger, MD, emeritus professor of medicine at the University of California, San Francisco, and coauthor of an editorial comment on the study, said in an interview that this study is noteworthy not only for its dual methodology, but for the quality of the data that matched patients at high risk for IE with prescription and dental records. “The fact that they were able to have those details in enough granularity that they knew whether a dental procedure was likely to meet the criteria for these more invasive exposures really broke it open from my perspective,” she said.

She called the low compliance rate with AHA guidelines “one of the most sobering points of this,” and said it should put clinicians on notice that they must do more to educate and engage with high-risk patients. “The lines of communication here are somewhat fraught; it’s a little bit of a hot potato,” she said. “It’s a really great communications opportunity to get the provider’s attention back on this. You’re a cardiologist; you have to have this conversation when you see your patient with a prosthetic valve or who’s had endocarditis every time they come in. There’s a whole litany, and it takes 3 minutes, but you have to do it.”

The study received funding from Delta Dental of Michigan Research Committee and Renaissance Health Service Corp., and Dr. Thornhill received support from Delta Dental Research and Data Institute for the study. Dr. Bolger participated in the 2007 and 2021 AHA statements on AP to prevent IE.

Two very different sets of clinical evidence have offered new twists on how nonadherence to cardiovascular medicines not only leads to suboptimal outcomes, but also complicates the data from clinical studies.

One study, a subanalysis of a major trial, outlined how taking more than the assigned therapy – that is, nonadherence by taking too much rather than too little – skewed results. The other was a trial demonstrating that early use of an invasive procedure is not a strategy to compensate for nonadherence to guideline-directed medical therapy (GDMT).

Bruce Jancin/Frontline Medical News

“Both studies provide a fresh reminder that nonadherence is a significant problem in cardiology overall, but also in the trial setting when we are trying to interpret study results,” explained Usam Baber, MD, director of interventional cardiology, University of Oklahoma Health, Oklahoma City, coauthor of an editorial accompanying the two published studies.

Dr. Baber was the first author of a unifying editorial that addressed the issues raised by each. In an interview, Dr. Baber said the studies had unique take-home messages but together highlight important issues of nonadherence.
 

MASTER DAPT: Too much medicine

The subanalysis was performed on data generated by MASTER DAPT, a study evaluating whether a relatively short course of dual-antiplatelet therapy (DAPT) in patients at high risk of bleeding could preserve protection against major adverse cardiovascular events (MACE) while reducing risk of adverse events. The problem was that nonadherence muddied the primary message.

In MASTER DAPT, 1 month of DAPT was compared with a standard therapy of at least 2 additional months of DAPT following revascularization and placement of a biodegradable polymer stent. Enrollment in the study was restricted to those with a high risk of bleeding, the report of the primary results showed.

The major message of MASTER DAPT was that the abbreviated course of DAPT was noninferior for preventing MACE but resulted in lower rates of clinically relevant bleeding in those patients without an indication for oral anticoagulation (OAC). In the subgroup with an indication for OAC, there was no bleeding benefit.

However, when the results were reexamined in the context of adherence, the benefit of the shorter course was found to be underestimated. Relative to 9.4% in the standard-therapy arm, the nonadherence rate in the experimental arm was 20.2%, most of whom did not stop therapy at 1 month. They instead remained on the antiplatelet therapy, failing to adhere to the study protocol.

This form of nonadherence, taking more DAPT than assigned, was particularly common in the group with an indication for oral anticoagulation (OAC). In this group, nearly 25% assigned to an abbreviated course remained on DAPT for more than 6 months.

In the intention-to-treat analysis, there was no difference between abbreviated and standard DAPT for MACE whether or not patients had an indication for OAC. In other words, the new analysis showed a reduced risk of bleeding among all patients, whether taking OAC or not after controlling for nonadherence.

In addition, this MASTER DAPT analysis found that a high proportion of patients taking OAC did not discontinue their single-antiplatelet therapy (SAPT) after 6 months as specified.

When correcting for this failure to adhere to the MASTER DAPT protocol in a patient population at high bleeding risk, the new analysis “suggests for the first time that discontinuation of SAPT at 6 months after percutaneous intervention is associated with less bleeding without an increase in ischemic events,” Marco Valgimigli, MD, PhD, director of clinical research, Inselspital University Hospital, Bern, Switzerland, reported in the Journal of the American College of Cardiology.

The findings “reinforce the importance of accounting and correcting for nonadherence” in order to reduce bias in the assessment of treatment effects, according to Dr. Valgimigli, principal investigator of MASTER DAPT and this substudy.

“The first interesting message from this study is that clinicians are reluctant to stop SAPT in these patients even in the setting of a randomized controlled trial,” Dr. Valgimigli said in an interview.

In addition, this substudy, which was prespecified in the MASTER DAPT protocol and employed “a very sophisticated methodology” to control for the effect of adherence, extends the value of a conservative approach to those who are candidates for OAC.

“The main clinical message is that SAPT needs to be discontinued after 6 months in OAC patients, and clinicians need to stop being reluctant to do so,” Dr. Valgimigli said. The data show “prolongation of SAPT increases bleeding risk without decreasing ischemic risk.”

In evaluating trial relevance, regulators prefer ITT analyses, but Dr. Baber pointed out that these can obscure the evidence of risk or benefit of a per-protocol analysis when patients take their medicine as prescribed.

“The technical message is that, when we are trying to apply results of a clinical trial to daily practice, we must understand nonadherence,” Dr. Baber said.

Dr. Baber pointed out that the lack of adherence in the case of MASTER DAPT appears to relate more to clinicians managing the patients than to the patients themselves, but it still speaks to the importance of understanding the effects of treatment in the context of the medicine rather than adherence to the medicine.

ISCHEMIA: Reconsidering adherence

In the ISCHEMIA trial, the goal was to evaluate whether an early invasive intervention might compensate to at least some degree for the persistent problem of nonadherence.

“If you are managing a patient that you know is at high risk of noncompliance, many clinicians are tempted to perform early revascularization. This was my bias. The thinking is that by offering an invasive therapy we are at least doing something to control their disease,” John A. Spertus, MD, clinical director of outcomes research, St. Luke’s Mid America Heart Institute, Kansas City, Mo., explained in an interview.

The study did not support the hypothesis. Patients with chronic coronary disease were randomized to a strategy of angiography and, if indicated, revascularization, or to receive GDMT alone. The health status was followed with the Seattle Angina Questionnaire (SAQ-7).

At 12 months, patients who were adherent to GDMT had better SAQ-7 scores than those who were nonadherent, regardless of the arm to which they were randomized. Conversely, there was no difference in SAQ-7 scores between the two groups when the nonadherent subgroups in each arm were compared.

“I think these data suggest that an interventional therapy does not absolve clinicians from the responsibility of educating patients about the importance of adhering to GDMT,” Dr. Spertus said.

In ISCHEMIA, 4,480 patients were randomized. At baseline assessment 27.8% were nonadherent to GDMT. The baselines SAQ-7 scores were worse in these patients relative to those who were adherent. At 12 months, nonadherence still correlated with worse SAQ-7 scores.

“These data dispel the belief that we might be benefiting nonadherent patients by moving more quickly to invasive procedures,” Dr. Spertus said.

In cardiovascular disease, particularly heart failure, adherence to GDMT has been associated numerous times with improved quality of life, according to Dr. Baber. However, he said, the ability of invasive procedures to modify the adverse impact of poor adherence to GDMT has not been well studied. This ISCHEMIA subanalysis only reinforces the message that GDMT adherence is a meaningful predictor of improved quality of life.

However, urging clinicians to work with patients to improve adherence is not a novel idea, according to Dr. Baber. The unmet need is effective and reliable strategies.

“There are so many different reasons that patients are nonadherent, so there are limited gains by focusing on just one of the issues,” Dr. Baber said. “I think the answer is a patient-centric approach in which clinicians deal with the specific issues facing the patient in front of them. I think there are data go suggest this yields better results.”

These two very different studies also show that poor adherence is an insidious issue. While the MASTER DAPT data reveal how nonadherence confuse trial data, the ISCHEMIA trial shows that some assumptions about circumventing the effects of nonadherence might not be accurate.

According to Dr. Baber, effective strategies to reduce nonadherence are available, but the problem deserves to be addressed more proactively in clinical trials and in patient care.

Dr. Baber reported financial relationships with AstraZeneca and Amgen. Dr. Spertus has financial relationships with Abbott, Bayer, Bristol-Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo. Dr. Valgimigli has financial relationships with more than 15 pharmaceutical companies, including Terumo, which provided funding for the MASTER DAPT trial.
 

Two very different sets of clinical evidence have offered new twists on how nonadherence to cardiovascular medicines not only leads to suboptimal outcomes, but also complicates the data from clinical studies.

One study, a subanalysis of a major trial, outlined how taking more than the assigned therapy – that is, nonadherence by taking too much rather than too little – skewed results. The other was a trial demonstrating that early use of an invasive procedure is not a strategy to compensate for nonadherence to guideline-directed medical therapy (GDMT).

Bruce Jancin/Frontline Medical News

“Both studies provide a fresh reminder that nonadherence is a significant problem in cardiology overall, but also in the trial setting when we are trying to interpret study results,” explained Usam Baber, MD, director of interventional cardiology, University of Oklahoma Health, Oklahoma City, coauthor of an editorial accompanying the two published studies.

Dr. Baber was the first author of a unifying editorial that addressed the issues raised by each. In an interview, Dr. Baber said the studies had unique take-home messages but together highlight important issues of nonadherence.
 

MASTER DAPT: Too much medicine

The subanalysis was performed on data generated by MASTER DAPT, a study evaluating whether a relatively short course of dual-antiplatelet therapy (DAPT) in patients at high risk of bleeding could preserve protection against major adverse cardiovascular events (MACE) while reducing risk of adverse events. The problem was that nonadherence muddied the primary message.

In MASTER DAPT, 1 month of DAPT was compared with a standard therapy of at least 2 additional months of DAPT following revascularization and placement of a biodegradable polymer stent. Enrollment in the study was restricted to those with a high risk of bleeding, the report of the primary results showed.

The major message of MASTER DAPT was that the abbreviated course of DAPT was noninferior for preventing MACE but resulted in lower rates of clinically relevant bleeding in those patients without an indication for oral anticoagulation (OAC). In the subgroup with an indication for OAC, there was no bleeding benefit.

However, when the results were reexamined in the context of adherence, the benefit of the shorter course was found to be underestimated. Relative to 9.4% in the standard-therapy arm, the nonadherence rate in the experimental arm was 20.2%, most of whom did not stop therapy at 1 month. They instead remained on the antiplatelet therapy, failing to adhere to the study protocol.

This form of nonadherence, taking more DAPT than assigned, was particularly common in the group with an indication for oral anticoagulation (OAC). In this group, nearly 25% assigned to an abbreviated course remained on DAPT for more than 6 months.

In the intention-to-treat analysis, there was no difference between abbreviated and standard DAPT for MACE whether or not patients had an indication for OAC. In other words, the new analysis showed a reduced risk of bleeding among all patients, whether taking OAC or not after controlling for nonadherence.

In addition, this MASTER DAPT analysis found that a high proportion of patients taking OAC did not discontinue their single-antiplatelet therapy (SAPT) after 6 months as specified.

When correcting for this failure to adhere to the MASTER DAPT protocol in a patient population at high bleeding risk, the new analysis “suggests for the first time that discontinuation of SAPT at 6 months after percutaneous intervention is associated with less bleeding without an increase in ischemic events,” Marco Valgimigli, MD, PhD, director of clinical research, Inselspital University Hospital, Bern, Switzerland, reported in the Journal of the American College of Cardiology.

The findings “reinforce the importance of accounting and correcting for nonadherence” in order to reduce bias in the assessment of treatment effects, according to Dr. Valgimigli, principal investigator of MASTER DAPT and this substudy.

“The first interesting message from this study is that clinicians are reluctant to stop SAPT in these patients even in the setting of a randomized controlled trial,” Dr. Valgimigli said in an interview.

In addition, this substudy, which was prespecified in the MASTER DAPT protocol and employed “a very sophisticated methodology” to control for the effect of adherence, extends the value of a conservative approach to those who are candidates for OAC.

“The main clinical message is that SAPT needs to be discontinued after 6 months in OAC patients, and clinicians need to stop being reluctant to do so,” Dr. Valgimigli said. The data show “prolongation of SAPT increases bleeding risk without decreasing ischemic risk.”

In evaluating trial relevance, regulators prefer ITT analyses, but Dr. Baber pointed out that these can obscure the evidence of risk or benefit of a per-protocol analysis when patients take their medicine as prescribed.

“The technical message is that, when we are trying to apply results of a clinical trial to daily practice, we must understand nonadherence,” Dr. Baber said.

Dr. Baber pointed out that the lack of adherence in the case of MASTER DAPT appears to relate more to clinicians managing the patients than to the patients themselves, but it still speaks to the importance of understanding the effects of treatment in the context of the medicine rather than adherence to the medicine.

ISCHEMIA: Reconsidering adherence

In the ISCHEMIA trial, the goal was to evaluate whether an early invasive intervention might compensate to at least some degree for the persistent problem of nonadherence.

“If you are managing a patient that you know is at high risk of noncompliance, many clinicians are tempted to perform early revascularization. This was my bias. The thinking is that by offering an invasive therapy we are at least doing something to control their disease,” John A. Spertus, MD, clinical director of outcomes research, St. Luke’s Mid America Heart Institute, Kansas City, Mo., explained in an interview.

The study did not support the hypothesis. Patients with chronic coronary disease were randomized to a strategy of angiography and, if indicated, revascularization, or to receive GDMT alone. The health status was followed with the Seattle Angina Questionnaire (SAQ-7).

At 12 months, patients who were adherent to GDMT had better SAQ-7 scores than those who were nonadherent, regardless of the arm to which they were randomized. Conversely, there was no difference in SAQ-7 scores between the two groups when the nonadherent subgroups in each arm were compared.

“I think these data suggest that an interventional therapy does not absolve clinicians from the responsibility of educating patients about the importance of adhering to GDMT,” Dr. Spertus said.

In ISCHEMIA, 4,480 patients were randomized. At baseline assessment 27.8% were nonadherent to GDMT. The baselines SAQ-7 scores were worse in these patients relative to those who were adherent. At 12 months, nonadherence still correlated with worse SAQ-7 scores.

“These data dispel the belief that we might be benefiting nonadherent patients by moving more quickly to invasive procedures,” Dr. Spertus said.

In cardiovascular disease, particularly heart failure, adherence to GDMT has been associated numerous times with improved quality of life, according to Dr. Baber. However, he said, the ability of invasive procedures to modify the adverse impact of poor adherence to GDMT has not been well studied. This ISCHEMIA subanalysis only reinforces the message that GDMT adherence is a meaningful predictor of improved quality of life.

However, urging clinicians to work with patients to improve adherence is not a novel idea, according to Dr. Baber. The unmet need is effective and reliable strategies.

“There are so many different reasons that patients are nonadherent, so there are limited gains by focusing on just one of the issues,” Dr. Baber said. “I think the answer is a patient-centric approach in which clinicians deal with the specific issues facing the patient in front of them. I think there are data go suggest this yields better results.”

These two very different studies also show that poor adherence is an insidious issue. While the MASTER DAPT data reveal how nonadherence confuse trial data, the ISCHEMIA trial shows that some assumptions about circumventing the effects of nonadherence might not be accurate.

According to Dr. Baber, effective strategies to reduce nonadherence are available, but the problem deserves to be addressed more proactively in clinical trials and in patient care.

Dr. Baber reported financial relationships with AstraZeneca and Amgen. Dr. Spertus has financial relationships with Abbott, Bayer, Bristol-Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo. Dr. Valgimigli has financial relationships with more than 15 pharmaceutical companies, including Terumo, which provided funding for the MASTER DAPT trial.
 

Two very different sets of clinical evidence have offered new twists on how nonadherence to cardiovascular medicines not only leads to suboptimal outcomes, but also complicates the data from clinical studies.

One study, a subanalysis of a major trial, outlined how taking more than the assigned therapy – that is, nonadherence by taking too much rather than too little – skewed results. The other was a trial demonstrating that early use of an invasive procedure is not a strategy to compensate for nonadherence to guideline-directed medical therapy (GDMT).

Bruce Jancin/Frontline Medical News

“Both studies provide a fresh reminder that nonadherence is a significant problem in cardiology overall, but also in the trial setting when we are trying to interpret study results,” explained Usam Baber, MD, director of interventional cardiology, University of Oklahoma Health, Oklahoma City, coauthor of an editorial accompanying the two published studies.

Dr. Baber was the first author of a unifying editorial that addressed the issues raised by each. In an interview, Dr. Baber said the studies had unique take-home messages but together highlight important issues of nonadherence.
 

MASTER DAPT: Too much medicine

The subanalysis was performed on data generated by MASTER DAPT, a study evaluating whether a relatively short course of dual-antiplatelet therapy (DAPT) in patients at high risk of bleeding could preserve protection against major adverse cardiovascular events (MACE) while reducing risk of adverse events. The problem was that nonadherence muddied the primary message.

In MASTER DAPT, 1 month of DAPT was compared with a standard therapy of at least 2 additional months of DAPT following revascularization and placement of a biodegradable polymer stent. Enrollment in the study was restricted to those with a high risk of bleeding, the report of the primary results showed.

The major message of MASTER DAPT was that the abbreviated course of DAPT was noninferior for preventing MACE but resulted in lower rates of clinically relevant bleeding in those patients without an indication for oral anticoagulation (OAC). In the subgroup with an indication for OAC, there was no bleeding benefit.

However, when the results were reexamined in the context of adherence, the benefit of the shorter course was found to be underestimated. Relative to 9.4% in the standard-therapy arm, the nonadherence rate in the experimental arm was 20.2%, most of whom did not stop therapy at 1 month. They instead remained on the antiplatelet therapy, failing to adhere to the study protocol.

This form of nonadherence, taking more DAPT than assigned, was particularly common in the group with an indication for oral anticoagulation (OAC). In this group, nearly 25% assigned to an abbreviated course remained on DAPT for more than 6 months.

In the intention-to-treat analysis, there was no difference between abbreviated and standard DAPT for MACE whether or not patients had an indication for OAC. In other words, the new analysis showed a reduced risk of bleeding among all patients, whether taking OAC or not after controlling for nonadherence.

In addition, this MASTER DAPT analysis found that a high proportion of patients taking OAC did not discontinue their single-antiplatelet therapy (SAPT) after 6 months as specified.

When correcting for this failure to adhere to the MASTER DAPT protocol in a patient population at high bleeding risk, the new analysis “suggests for the first time that discontinuation of SAPT at 6 months after percutaneous intervention is associated with less bleeding without an increase in ischemic events,” Marco Valgimigli, MD, PhD, director of clinical research, Inselspital University Hospital, Bern, Switzerland, reported in the Journal of the American College of Cardiology.

The findings “reinforce the importance of accounting and correcting for nonadherence” in order to reduce bias in the assessment of treatment effects, according to Dr. Valgimigli, principal investigator of MASTER DAPT and this substudy.

“The first interesting message from this study is that clinicians are reluctant to stop SAPT in these patients even in the setting of a randomized controlled trial,” Dr. Valgimigli said in an interview.

In addition, this substudy, which was prespecified in the MASTER DAPT protocol and employed “a very sophisticated methodology” to control for the effect of adherence, extends the value of a conservative approach to those who are candidates for OAC.

“The main clinical message is that SAPT needs to be discontinued after 6 months in OAC patients, and clinicians need to stop being reluctant to do so,” Dr. Valgimigli said. The data show “prolongation of SAPT increases bleeding risk without decreasing ischemic risk.”

In evaluating trial relevance, regulators prefer ITT analyses, but Dr. Baber pointed out that these can obscure the evidence of risk or benefit of a per-protocol analysis when patients take their medicine as prescribed.

“The technical message is that, when we are trying to apply results of a clinical trial to daily practice, we must understand nonadherence,” Dr. Baber said.

Dr. Baber pointed out that the lack of adherence in the case of MASTER DAPT appears to relate more to clinicians managing the patients than to the patients themselves, but it still speaks to the importance of understanding the effects of treatment in the context of the medicine rather than adherence to the medicine.

ISCHEMIA: Reconsidering adherence

In the ISCHEMIA trial, the goal was to evaluate whether an early invasive intervention might compensate to at least some degree for the persistent problem of nonadherence.

“If you are managing a patient that you know is at high risk of noncompliance, many clinicians are tempted to perform early revascularization. This was my bias. The thinking is that by offering an invasive therapy we are at least doing something to control their disease,” John A. Spertus, MD, clinical director of outcomes research, St. Luke’s Mid America Heart Institute, Kansas City, Mo., explained in an interview.

The study did not support the hypothesis. Patients with chronic coronary disease were randomized to a strategy of angiography and, if indicated, revascularization, or to receive GDMT alone. The health status was followed with the Seattle Angina Questionnaire (SAQ-7).

At 12 months, patients who were adherent to GDMT had better SAQ-7 scores than those who were nonadherent, regardless of the arm to which they were randomized. Conversely, there was no difference in SAQ-7 scores between the two groups when the nonadherent subgroups in each arm were compared.

“I think these data suggest that an interventional therapy does not absolve clinicians from the responsibility of educating patients about the importance of adhering to GDMT,” Dr. Spertus said.

In ISCHEMIA, 4,480 patients were randomized. At baseline assessment 27.8% were nonadherent to GDMT. The baselines SAQ-7 scores were worse in these patients relative to those who were adherent. At 12 months, nonadherence still correlated with worse SAQ-7 scores.

“These data dispel the belief that we might be benefiting nonadherent patients by moving more quickly to invasive procedures,” Dr. Spertus said.

In cardiovascular disease, particularly heart failure, adherence to GDMT has been associated numerous times with improved quality of life, according to Dr. Baber. However, he said, the ability of invasive procedures to modify the adverse impact of poor adherence to GDMT has not been well studied. This ISCHEMIA subanalysis only reinforces the message that GDMT adherence is a meaningful predictor of improved quality of life.

However, urging clinicians to work with patients to improve adherence is not a novel idea, according to Dr. Baber. The unmet need is effective and reliable strategies.

“There are so many different reasons that patients are nonadherent, so there are limited gains by focusing on just one of the issues,” Dr. Baber said. “I think the answer is a patient-centric approach in which clinicians deal with the specific issues facing the patient in front of them. I think there are data go suggest this yields better results.”

These two very different studies also show that poor adherence is an insidious issue. While the MASTER DAPT data reveal how nonadherence confuse trial data, the ISCHEMIA trial shows that some assumptions about circumventing the effects of nonadherence might not be accurate.

According to Dr. Baber, effective strategies to reduce nonadherence are available, but the problem deserves to be addressed more proactively in clinical trials and in patient care.

Dr. Baber reported financial relationships with AstraZeneca and Amgen. Dr. Spertus has financial relationships with Abbott, Bayer, Bristol-Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo. Dr. Valgimigli has financial relationships with more than 15 pharmaceutical companies, including Terumo, which provided funding for the MASTER DAPT trial.
 

Early improvement of left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) is associated with improved all-cause and cardiac death at 5 years in patients with severe aortic stenosis and LVEF less than 50%, new research shows.

Further analyses revealed a significant interaction by sex, with the mortality benefit largely in women.

“It’s absolutely fascinating,” senior author Sammy Elmariah, MD, Massachusetts General Hospital, Boston, said of the finding. “We know that women are more likely to have concentric hypertrophy, that they have lesser degrees of fibrosis, and smaller ventricles, and, of course, they’re in general less affected by coronary artery disease and MIs [myocardial infarctions]. All of those things in my mind, at least that’s what I assumed ahead of time, would make it more likely for women’s hearts to recover.”

“But that’s actually not what we found,” he continued. “We didn’t see a difference between the sexes in terms of likelihood of recovery. But what we saw is that the survival benefit, that associates with improvement in EF, was almost completely driven by women. So women really seem to be reaping that benefit in a manner that is unique and very different from what we saw in men.”

Dr. Elmariah noted that the reason for this benefit is unclear but points to the differences in biology for LV remodeling. “Clearly there are several details there that warrant further attention and more research.”

Suzanne J. Baron, MD, director of interventional cardiology research at Lahey Hospital and Medical Center, Burlington, Mass., said in an email that the finding of a substantial long-term survival benefit was “a bit surprising.”

Several studies have suggested that women may derive a greater benefit from TAVR versus surgical aortic valve replacement, and meta-analyses have demonstrated short and intermediate-term survival after TAVR is better in women, compared with in men, she pointed out. However, the mediating mechanism for this finding has never been clearly elucidated.

“Certainly, the sex differences in LVEF improvement after TAVR observed in this study, which could be related to sex differences in LV remodeling and LV mass regression, may now give us a clue as to why these sex-specific survival differences after TAVR persist,” Dr. Baron said.
 

More data amassed

Previous research in smaller cohorts with follow-up out to 1 year have shown an association between early LVEF improvement after TAVR and better survival. This includes a 2013 study by the investigators in high-risk patients in PARTNER-1 and a separate 2016 study in patients in the CoreValve extreme and high surgical risk trials.

Now, with longer follow-up amassed, the investigators examined data from 659 high- or intermediate-risk patients with severe stenosis and LVEF less than 50% who underwent transfemoral TAVR in the PARTNER 1, 2, and S3 trials and registries between July 2007 and April 2015.

Their mean age was 82.4 years, 71% were men, and 89.7% were White individuals. During the study period, 55.6% of the cohort died.

As reported in JAMA Cardiology, 32.8% of patients had early LVEF improvement, defined as an increase of at least 10% percentage points at 30 days after TAVR (mean change, 16.4%).

This compares with about 50%-60% of patients in the earlier studies, likely owing to the relatively higher baseline LVEF, especially in the intermediate-risk cohort, the authors suggested.

Independent predictors of lower likelihood of early LVEF improvement were previous MI, diabetes, cancer, higher baseline LVEF, larger LV end-diastolic diameter, and larger aortic valve area (AVA), whereas higher body mass index and higher stroke volume index predicted greater likelihood of LV recovery.

At 5 years, patients with versus without improved early LV improvement had lower risks of all-cause death (50.0% vs. 58.4%; P = .04) and cardiac death (29.5% vs. 38.1%; P = .05).

In multivariable analyses, each 5%-point increase in LVEF after TAVR was associated with a 6% lower risk of all-cause death (hazard ratio [HR], 0.94; P = .04) and 10% lower risk of cardiac death (HR, 0.90; P = .02).

Restricted cubic spline analysis demonstrated an inflection point above a 10% change in LVEF beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement.

There were no significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire score at 5 years in patients with and without early LVEF improvement.

“I think what this really gets to is what is the reason behind the LV dysfunction in the first place,” said Dr. Elmariah, soon to be joining the University of California, San Francisco. “We know that TAVR cures aortic stenosis, so if the LV dysfunction is primarily related to the valve itself, hopefully those patients are going to recover.”

On the other hand, if the patient has LV dysfunction because of a prior myocardial infarction or cardiomyopathy and then developed aortic stenosis, “you can treat the aortic stenosis but the heart is still diseased from whatever process was affecting it previously and so it’s not likely to recover in those scenarios,” he added.

The results can be used for counseling patients and highlight the need to optimize goal-directed medical therapy in those with valvular heart disease, Dr. Elmariah suggested.

“Often, patients with aortic stenosis are on miniscule doses of many of the heart failure agents because people are worried about the hemodynamic consequences and they’re worried that patients won’t tolerate these medications,” he said. “But it’s very important for us to aggressively try to treat the heart failure that is affecting these patients in order to hopefully increase the chances that their left ventricles will recover and, hopefully, that they will have improved survival.”

Dr. Baron said that “this study clearly demonstrates that patients with reduced LVEF and severe aortic stenosis can benefit from TAVR and that early improvement in LVEF is an important prognostic marker for this population.”

In Dr. Baron and colleagues’ earlier analysis of 11,000 patients who underwent TAVR as part of the transcatheter valve therapy registry, only low aortic valve gradient but not LV dysfunction was associated with higher adjusted 1-year mortality. Asked about the finding, she noted that patients were evaluated based on LV function at baseline and not for a difference in outcomes based on LVEF improvement after TAVR.

“As such, I think that these two studies are actually complementary,” Dr. Baron said. “Together, they suggest that a low LVEF should not preclude a patient from receiving TAVR and if the patient does experience a 10% increase in LVEF after TAVR, then their 5-year prognosis is improved.”

Dr. Elmariah reports grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Medtronic, and Svelte Medical and has received consulting fees from Medtronic and AstraZeneca. Coauthor disclosures are listed in the paper. The PARTNER trials and registries and this analysis were supported by Edwards Lifesciences. Edwards was involved in the design and conduct of the study including collection, management, analysis, and interpretation of the data. Dr. Baron reports receiving research grant funding from Abiomed and Boston Scientific; consulting/medical advisory board fees from Boston Scientific, Shockwave and Biotronik; and speaking honoraria from Medtronic and Zoll.

A version of this article first appeared on Medscape.com.

Early improvement of left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) is associated with improved all-cause and cardiac death at 5 years in patients with severe aortic stenosis and LVEF less than 50%, new research shows.

Further analyses revealed a significant interaction by sex, with the mortality benefit largely in women.

“It’s absolutely fascinating,” senior author Sammy Elmariah, MD, Massachusetts General Hospital, Boston, said of the finding. “We know that women are more likely to have concentric hypertrophy, that they have lesser degrees of fibrosis, and smaller ventricles, and, of course, they’re in general less affected by coronary artery disease and MIs [myocardial infarctions]. All of those things in my mind, at least that’s what I assumed ahead of time, would make it more likely for women’s hearts to recover.”

“But that’s actually not what we found,” he continued. “We didn’t see a difference between the sexes in terms of likelihood of recovery. But what we saw is that the survival benefit, that associates with improvement in EF, was almost completely driven by women. So women really seem to be reaping that benefit in a manner that is unique and very different from what we saw in men.”

Dr. Elmariah noted that the reason for this benefit is unclear but points to the differences in biology for LV remodeling. “Clearly there are several details there that warrant further attention and more research.”

Suzanne J. Baron, MD, director of interventional cardiology research at Lahey Hospital and Medical Center, Burlington, Mass., said in an email that the finding of a substantial long-term survival benefit was “a bit surprising.”

Several studies have suggested that women may derive a greater benefit from TAVR versus surgical aortic valve replacement, and meta-analyses have demonstrated short and intermediate-term survival after TAVR is better in women, compared with in men, she pointed out. However, the mediating mechanism for this finding has never been clearly elucidated.

“Certainly, the sex differences in LVEF improvement after TAVR observed in this study, which could be related to sex differences in LV remodeling and LV mass regression, may now give us a clue as to why these sex-specific survival differences after TAVR persist,” Dr. Baron said.
 

More data amassed

Previous research in smaller cohorts with follow-up out to 1 year have shown an association between early LVEF improvement after TAVR and better survival. This includes a 2013 study by the investigators in high-risk patients in PARTNER-1 and a separate 2016 study in patients in the CoreValve extreme and high surgical risk trials.

Now, with longer follow-up amassed, the investigators examined data from 659 high- or intermediate-risk patients with severe stenosis and LVEF less than 50% who underwent transfemoral TAVR in the PARTNER 1, 2, and S3 trials and registries between July 2007 and April 2015.

Their mean age was 82.4 years, 71% were men, and 89.7% were White individuals. During the study period, 55.6% of the cohort died.

As reported in JAMA Cardiology, 32.8% of patients had early LVEF improvement, defined as an increase of at least 10% percentage points at 30 days after TAVR (mean change, 16.4%).

This compares with about 50%-60% of patients in the earlier studies, likely owing to the relatively higher baseline LVEF, especially in the intermediate-risk cohort, the authors suggested.

Independent predictors of lower likelihood of early LVEF improvement were previous MI, diabetes, cancer, higher baseline LVEF, larger LV end-diastolic diameter, and larger aortic valve area (AVA), whereas higher body mass index and higher stroke volume index predicted greater likelihood of LV recovery.

At 5 years, patients with versus without improved early LV improvement had lower risks of all-cause death (50.0% vs. 58.4%; P = .04) and cardiac death (29.5% vs. 38.1%; P = .05).

In multivariable analyses, each 5%-point increase in LVEF after TAVR was associated with a 6% lower risk of all-cause death (hazard ratio [HR], 0.94; P = .04) and 10% lower risk of cardiac death (HR, 0.90; P = .02).

Restricted cubic spline analysis demonstrated an inflection point above a 10% change in LVEF beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement.

There were no significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire score at 5 years in patients with and without early LVEF improvement.

“I think what this really gets to is what is the reason behind the LV dysfunction in the first place,” said Dr. Elmariah, soon to be joining the University of California, San Francisco. “We know that TAVR cures aortic stenosis, so if the LV dysfunction is primarily related to the valve itself, hopefully those patients are going to recover.”

On the other hand, if the patient has LV dysfunction because of a prior myocardial infarction or cardiomyopathy and then developed aortic stenosis, “you can treat the aortic stenosis but the heart is still diseased from whatever process was affecting it previously and so it’s not likely to recover in those scenarios,” he added.

The results can be used for counseling patients and highlight the need to optimize goal-directed medical therapy in those with valvular heart disease, Dr. Elmariah suggested.

“Often, patients with aortic stenosis are on miniscule doses of many of the heart failure agents because people are worried about the hemodynamic consequences and they’re worried that patients won’t tolerate these medications,” he said. “But it’s very important for us to aggressively try to treat the heart failure that is affecting these patients in order to hopefully increase the chances that their left ventricles will recover and, hopefully, that they will have improved survival.”

Dr. Baron said that “this study clearly demonstrates that patients with reduced LVEF and severe aortic stenosis can benefit from TAVR and that early improvement in LVEF is an important prognostic marker for this population.”

In Dr. Baron and colleagues’ earlier analysis of 11,000 patients who underwent TAVR as part of the transcatheter valve therapy registry, only low aortic valve gradient but not LV dysfunction was associated with higher adjusted 1-year mortality. Asked about the finding, she noted that patients were evaluated based on LV function at baseline and not for a difference in outcomes based on LVEF improvement after TAVR.

“As such, I think that these two studies are actually complementary,” Dr. Baron said. “Together, they suggest that a low LVEF should not preclude a patient from receiving TAVR and if the patient does experience a 10% increase in LVEF after TAVR, then their 5-year prognosis is improved.”

Dr. Elmariah reports grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Medtronic, and Svelte Medical and has received consulting fees from Medtronic and AstraZeneca. Coauthor disclosures are listed in the paper. The PARTNER trials and registries and this analysis were supported by Edwards Lifesciences. Edwards was involved in the design and conduct of the study including collection, management, analysis, and interpretation of the data. Dr. Baron reports receiving research grant funding from Abiomed and Boston Scientific; consulting/medical advisory board fees from Boston Scientific, Shockwave and Biotronik; and speaking honoraria from Medtronic and Zoll.

A version of this article first appeared on Medscape.com.

Early improvement of left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) is associated with improved all-cause and cardiac death at 5 years in patients with severe aortic stenosis and LVEF less than 50%, new research shows.

Further analyses revealed a significant interaction by sex, with the mortality benefit largely in women.

“It’s absolutely fascinating,” senior author Sammy Elmariah, MD, Massachusetts General Hospital, Boston, said of the finding. “We know that women are more likely to have concentric hypertrophy, that they have lesser degrees of fibrosis, and smaller ventricles, and, of course, they’re in general less affected by coronary artery disease and MIs [myocardial infarctions]. All of those things in my mind, at least that’s what I assumed ahead of time, would make it more likely for women’s hearts to recover.”

“But that’s actually not what we found,” he continued. “We didn’t see a difference between the sexes in terms of likelihood of recovery. But what we saw is that the survival benefit, that associates with improvement in EF, was almost completely driven by women. So women really seem to be reaping that benefit in a manner that is unique and very different from what we saw in men.”

Dr. Elmariah noted that the reason for this benefit is unclear but points to the differences in biology for LV remodeling. “Clearly there are several details there that warrant further attention and more research.”

Suzanne J. Baron, MD, director of interventional cardiology research at Lahey Hospital and Medical Center, Burlington, Mass., said in an email that the finding of a substantial long-term survival benefit was “a bit surprising.”

Several studies have suggested that women may derive a greater benefit from TAVR versus surgical aortic valve replacement, and meta-analyses have demonstrated short and intermediate-term survival after TAVR is better in women, compared with in men, she pointed out. However, the mediating mechanism for this finding has never been clearly elucidated.

“Certainly, the sex differences in LVEF improvement after TAVR observed in this study, which could be related to sex differences in LV remodeling and LV mass regression, may now give us a clue as to why these sex-specific survival differences after TAVR persist,” Dr. Baron said.
 

More data amassed

Previous research in smaller cohorts with follow-up out to 1 year have shown an association between early LVEF improvement after TAVR and better survival. This includes a 2013 study by the investigators in high-risk patients in PARTNER-1 and a separate 2016 study in patients in the CoreValve extreme and high surgical risk trials.

Now, with longer follow-up amassed, the investigators examined data from 659 high- or intermediate-risk patients with severe stenosis and LVEF less than 50% who underwent transfemoral TAVR in the PARTNER 1, 2, and S3 trials and registries between July 2007 and April 2015.

Their mean age was 82.4 years, 71% were men, and 89.7% were White individuals. During the study period, 55.6% of the cohort died.

As reported in JAMA Cardiology, 32.8% of patients had early LVEF improvement, defined as an increase of at least 10% percentage points at 30 days after TAVR (mean change, 16.4%).

This compares with about 50%-60% of patients in the earlier studies, likely owing to the relatively higher baseline LVEF, especially in the intermediate-risk cohort, the authors suggested.

Independent predictors of lower likelihood of early LVEF improvement were previous MI, diabetes, cancer, higher baseline LVEF, larger LV end-diastolic diameter, and larger aortic valve area (AVA), whereas higher body mass index and higher stroke volume index predicted greater likelihood of LV recovery.

At 5 years, patients with versus without improved early LV improvement had lower risks of all-cause death (50.0% vs. 58.4%; P = .04) and cardiac death (29.5% vs. 38.1%; P = .05).

In multivariable analyses, each 5%-point increase in LVEF after TAVR was associated with a 6% lower risk of all-cause death (hazard ratio [HR], 0.94; P = .04) and 10% lower risk of cardiac death (HR, 0.90; P = .02).

Restricted cubic spline analysis demonstrated an inflection point above a 10% change in LVEF beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement.

There were no significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire score at 5 years in patients with and without early LVEF improvement.

“I think what this really gets to is what is the reason behind the LV dysfunction in the first place,” said Dr. Elmariah, soon to be joining the University of California, San Francisco. “We know that TAVR cures aortic stenosis, so if the LV dysfunction is primarily related to the valve itself, hopefully those patients are going to recover.”

On the other hand, if the patient has LV dysfunction because of a prior myocardial infarction or cardiomyopathy and then developed aortic stenosis, “you can treat the aortic stenosis but the heart is still diseased from whatever process was affecting it previously and so it’s not likely to recover in those scenarios,” he added.

The results can be used for counseling patients and highlight the need to optimize goal-directed medical therapy in those with valvular heart disease, Dr. Elmariah suggested.

“Often, patients with aortic stenosis are on miniscule doses of many of the heart failure agents because people are worried about the hemodynamic consequences and they’re worried that patients won’t tolerate these medications,” he said. “But it’s very important for us to aggressively try to treat the heart failure that is affecting these patients in order to hopefully increase the chances that their left ventricles will recover and, hopefully, that they will have improved survival.”

Dr. Baron said that “this study clearly demonstrates that patients with reduced LVEF and severe aortic stenosis can benefit from TAVR and that early improvement in LVEF is an important prognostic marker for this population.”

In Dr. Baron and colleagues’ earlier analysis of 11,000 patients who underwent TAVR as part of the transcatheter valve therapy registry, only low aortic valve gradient but not LV dysfunction was associated with higher adjusted 1-year mortality. Asked about the finding, she noted that patients were evaluated based on LV function at baseline and not for a difference in outcomes based on LVEF improvement after TAVR.

“As such, I think that these two studies are actually complementary,” Dr. Baron said. “Together, they suggest that a low LVEF should not preclude a patient from receiving TAVR and if the patient does experience a 10% increase in LVEF after TAVR, then their 5-year prognosis is improved.”

Dr. Elmariah reports grants from the American Heart Association, National Institutes of Health, Edwards Lifesciences, Medtronic, and Svelte Medical and has received consulting fees from Medtronic and AstraZeneca. Coauthor disclosures are listed in the paper. The PARTNER trials and registries and this analysis were supported by Edwards Lifesciences. Edwards was involved in the design and conduct of the study including collection, management, analysis, and interpretation of the data. Dr. Baron reports receiving research grant funding from Abiomed and Boston Scientific; consulting/medical advisory board fees from Boston Scientific, Shockwave and Biotronik; and speaking honoraria from Medtronic and Zoll.

A version of this article first appeared on Medscape.com.

Patients who take beta-blockers or antiplatelet agents are lowering their risk for cardiovascular events, but the protection may fall short for those who spend time outdoors on hot summer days, hints a limited analysis published as a letter in Nature Cardiovascular Research.

Patients taking either a beta-blocker or antiplatelet, or both medications together, appeared at elevated risk for nonfatal acute MI specifically on days when the weather turned hot, suggests the registry cohort study that covered 14 years of clinical and meteorologic data.

rottadana/Thinkstock

“The take-away message is not that patients should stop using these two medications, by no means. We’re raising cautions for patients taking them, to watch out for themselves during high-heat days,” lead author Kai Chen, PhD, Yale University, New Haven, Conn., said in an interview.

“We’re not giving the message that these drugs have harmful effects” because the nature of the links between the medications and MI in the study, with its potential for confounding, remain unknown, said Dr. Chen, from the department of environmental health sciences and Yale Center on Climate Change and Health.

For example, patients who take beta-blockers or antiplatelets tend to be sicker than patients not on the drugs, which could make heat-related MI more likely, and the drugs wrongly appear to be culprits, he observed. The analysis contained signals that could support either scenario.

The study is based on cases of nonfatal MI in Augsburg, Germany, that are part of the MONICA-KORA MI registry. The odds of a heat-related nonfatal MI, it suggests, were increased 63% among patients taking antiplatelets and by 65% among those on beta-blockers, compared with those not on these drugs. The odds went up by 75% among those on both drug classes, but the risks weren’t raised in patients not taking them.
 

Rising heat-related MI

Chen said analysis was inspired by a 2019 report – also based on MONICA-KORA, from many of the same authors and using similar methods to track events by daily air temperature – that showed a rising trend for heat-related MI and declining rate for MI related to cold weather from 1987 to 2014. A next step, he figured, would be to determine whether the MI risk trends were associated with any cardiovascular medications.

The current study’s signal of risk related to antiplatelets and beta-blockers did not emerge for ACE inhibitors, calcium-channel blockers, or diuretics. Statins showed a link to increased nonfatal MI risk, but solely among participants aged younger than 60 years, who were also far less likely to have pre-existing coronary heart disease (CHD). He and his colleagues chose not to highlight that finding, Dr. Chen said, because the age subgroup analysis was grossly underpowered.

The overall analysis involved 2,494 cases of nonfatal MI that occurred during the warmer months – May to September – from 2001 to 2014. It was limited to nonfatal cases – those with at least a month of survival after hospital admission – because of insufficient data on medication use associated with fatal MIs, the report states.

Nonfatal MIs were defined as heat-related if they struck on days reaching the 95th percentile for temperature across the 14 years, in this case 24.2 °C (about 75.6 °F), relative to the average temperature of lowest nonfatal MI risk across the cohort, 7.5 °C (about 45.5 °F).

Patients served as both cases and their own controls, in that air temperature exposures on the day of their MI (case day) were compared with the remaining same days of the week in the same calendar month (control days). That approach, the report stated, “automatically controls for long-term time trends, seasonality, day of the week, and time-invariant confounders (for example, pre-existing cardiovascular disease).”

The odds ratio for heat-related MI for patients on antiplatelets was 1.63 (95% confidence interval, 1.07-2.46), and for antiplatelet nonusers was 0.94 (95% CI, 0.68-1.29). The difference between the two ratios was significant (P = .04).

The corresponding OR for patients taking beta-blockers was 1.65 (95% CI, 1.11-2.45), and for nonusers of beta-blockers was 0.90 (95% CI, 0.64-1.26). Again, the OR difference was significant (P = .02).

The ORs for users of both medication classes and nonusers of either med class, respectively, were 1.75 (95% CI, 1.12-2.73) and 0.84 (95% CI, 0.59-1.19). The latter OR was significantly lower than former (P = .01).

In a sign that antiplatelet and beta-blocker use might have been just a marker for sicker patients who were more vulnerable to heat-related MI, Chen said, the nonfatal MI risk was significantly elevated (OR, 2.17; 95% CI, 1.40-3.38) among patients with pre-existing CHD, but not among those free of pre-existing CHD (OR, 0.88; 95% CI, 0.65-1.20); the odds difference was P < .01.

That signal of confounding by indication is somewhat countered, the report states, by variations in nonfatal MI risk by age group. The increased chances of an event seen overall in relation to beta-blockers and antiplatelets were more pronounced among the 39% of patients aged 25-59 years (P < .01). That’s in spite that group’s lower CHD prevalence. The risk elevation solely among the older patients was attenuated and rendered nonsignificant, even with their greater CHD burden, the report noted.

The report speculates on a potential mechanism by which beta-blockers, at least, might conceivably raise the risk for heat-related MI. “Beta-receptor blockers inhibit skin vasodilation, resulting in reduced heat dissipation through convection and, at the same time, could intensify the blood-pressure-lowering effect of other antihypertensive drugs, which then could lead to syncope.”

Beta-blockers, Dr. Chen said, “can mechanistically make people more vulnerable to heat. That’s one potential explanation. Or it could be that these people taking the medications are just sicker. Whatever the reasons, the phenomenon we observed is that these patients taking these two medications are at higher risk during high-temperature days.”

Dr. Chen and the other authors declare no competing interests.

A version of this article first appeared on Medscape.com.

Patients who take beta-blockers or antiplatelet agents are lowering their risk for cardiovascular events, but the protection may fall short for those who spend time outdoors on hot summer days, hints a limited analysis published as a letter in Nature Cardiovascular Research.

Patients taking either a beta-blocker or antiplatelet, or both medications together, appeared at elevated risk for nonfatal acute MI specifically on days when the weather turned hot, suggests the registry cohort study that covered 14 years of clinical and meteorologic data.

rottadana/Thinkstock

“The take-away message is not that patients should stop using these two medications, by no means. We’re raising cautions for patients taking them, to watch out for themselves during high-heat days,” lead author Kai Chen, PhD, Yale University, New Haven, Conn., said in an interview.

“We’re not giving the message that these drugs have harmful effects” because the nature of the links between the medications and MI in the study, with its potential for confounding, remain unknown, said Dr. Chen, from the department of environmental health sciences and Yale Center on Climate Change and Health.

For example, patients who take beta-blockers or antiplatelets tend to be sicker than patients not on the drugs, which could make heat-related MI more likely, and the drugs wrongly appear to be culprits, he observed. The analysis contained signals that could support either scenario.

The study is based on cases of nonfatal MI in Augsburg, Germany, that are part of the MONICA-KORA MI registry. The odds of a heat-related nonfatal MI, it suggests, were increased 63% among patients taking antiplatelets and by 65% among those on beta-blockers, compared with those not on these drugs. The odds went up by 75% among those on both drug classes, but the risks weren’t raised in patients not taking them.
 

Rising heat-related MI

Chen said analysis was inspired by a 2019 report – also based on MONICA-KORA, from many of the same authors and using similar methods to track events by daily air temperature – that showed a rising trend for heat-related MI and declining rate for MI related to cold weather from 1987 to 2014. A next step, he figured, would be to determine whether the MI risk trends were associated with any cardiovascular medications.

The current study’s signal of risk related to antiplatelets and beta-blockers did not emerge for ACE inhibitors, calcium-channel blockers, or diuretics. Statins showed a link to increased nonfatal MI risk, but solely among participants aged younger than 60 years, who were also far less likely to have pre-existing coronary heart disease (CHD). He and his colleagues chose not to highlight that finding, Dr. Chen said, because the age subgroup analysis was grossly underpowered.

The overall analysis involved 2,494 cases of nonfatal MI that occurred during the warmer months – May to September – from 2001 to 2014. It was limited to nonfatal cases – those with at least a month of survival after hospital admission – because of insufficient data on medication use associated with fatal MIs, the report states.

Nonfatal MIs were defined as heat-related if they struck on days reaching the 95th percentile for temperature across the 14 years, in this case 24.2 °C (about 75.6 °F), relative to the average temperature of lowest nonfatal MI risk across the cohort, 7.5 °C (about 45.5 °F).

Patients served as both cases and their own controls, in that air temperature exposures on the day of their MI (case day) were compared with the remaining same days of the week in the same calendar month (control days). That approach, the report stated, “automatically controls for long-term time trends, seasonality, day of the week, and time-invariant confounders (for example, pre-existing cardiovascular disease).”

The odds ratio for heat-related MI for patients on antiplatelets was 1.63 (95% confidence interval, 1.07-2.46), and for antiplatelet nonusers was 0.94 (95% CI, 0.68-1.29). The difference between the two ratios was significant (P = .04).

The corresponding OR for patients taking beta-blockers was 1.65 (95% CI, 1.11-2.45), and for nonusers of beta-blockers was 0.90 (95% CI, 0.64-1.26). Again, the OR difference was significant (P = .02).

The ORs for users of both medication classes and nonusers of either med class, respectively, were 1.75 (95% CI, 1.12-2.73) and 0.84 (95% CI, 0.59-1.19). The latter OR was significantly lower than former (P = .01).

In a sign that antiplatelet and beta-blocker use might have been just a marker for sicker patients who were more vulnerable to heat-related MI, Chen said, the nonfatal MI risk was significantly elevated (OR, 2.17; 95% CI, 1.40-3.38) among patients with pre-existing CHD, but not among those free of pre-existing CHD (OR, 0.88; 95% CI, 0.65-1.20); the odds difference was P < .01.

That signal of confounding by indication is somewhat countered, the report states, by variations in nonfatal MI risk by age group. The increased chances of an event seen overall in relation to beta-blockers and antiplatelets were more pronounced among the 39% of patients aged 25-59 years (P < .01). That’s in spite that group’s lower CHD prevalence. The risk elevation solely among the older patients was attenuated and rendered nonsignificant, even with their greater CHD burden, the report noted.

The report speculates on a potential mechanism by which beta-blockers, at least, might conceivably raise the risk for heat-related MI. “Beta-receptor blockers inhibit skin vasodilation, resulting in reduced heat dissipation through convection and, at the same time, could intensify the blood-pressure-lowering effect of other antihypertensive drugs, which then could lead to syncope.”

Beta-blockers, Dr. Chen said, “can mechanistically make people more vulnerable to heat. That’s one potential explanation. Or it could be that these people taking the medications are just sicker. Whatever the reasons, the phenomenon we observed is that these patients taking these two medications are at higher risk during high-temperature days.”

Dr. Chen and the other authors declare no competing interests.

A version of this article first appeared on Medscape.com.

Patients who take beta-blockers or antiplatelet agents are lowering their risk for cardiovascular events, but the protection may fall short for those who spend time outdoors on hot summer days, hints a limited analysis published as a letter in Nature Cardiovascular Research.

Patients taking either a beta-blocker or antiplatelet, or both medications together, appeared at elevated risk for nonfatal acute MI specifically on days when the weather turned hot, suggests the registry cohort study that covered 14 years of clinical and meteorologic data.

rottadana/Thinkstock

“The take-away message is not that patients should stop using these two medications, by no means. We’re raising cautions for patients taking them, to watch out for themselves during high-heat days,” lead author Kai Chen, PhD, Yale University, New Haven, Conn., said in an interview.

“We’re not giving the message that these drugs have harmful effects” because the nature of the links between the medications and MI in the study, with its potential for confounding, remain unknown, said Dr. Chen, from the department of environmental health sciences and Yale Center on Climate Change and Health.

For example, patients who take beta-blockers or antiplatelets tend to be sicker than patients not on the drugs, which could make heat-related MI more likely, and the drugs wrongly appear to be culprits, he observed. The analysis contained signals that could support either scenario.

The study is based on cases of nonfatal MI in Augsburg, Germany, that are part of the MONICA-KORA MI registry. The odds of a heat-related nonfatal MI, it suggests, were increased 63% among patients taking antiplatelets and by 65% among those on beta-blockers, compared with those not on these drugs. The odds went up by 75% among those on both drug classes, but the risks weren’t raised in patients not taking them.
 

Rising heat-related MI

Chen said analysis was inspired by a 2019 report – also based on MONICA-KORA, from many of the same authors and using similar methods to track events by daily air temperature – that showed a rising trend for heat-related MI and declining rate for MI related to cold weather from 1987 to 2014. A next step, he figured, would be to determine whether the MI risk trends were associated with any cardiovascular medications.

The current study’s signal of risk related to antiplatelets and beta-blockers did not emerge for ACE inhibitors, calcium-channel blockers, or diuretics. Statins showed a link to increased nonfatal MI risk, but solely among participants aged younger than 60 years, who were also far less likely to have pre-existing coronary heart disease (CHD). He and his colleagues chose not to highlight that finding, Dr. Chen said, because the age subgroup analysis was grossly underpowered.

The overall analysis involved 2,494 cases of nonfatal MI that occurred during the warmer months – May to September – from 2001 to 2014. It was limited to nonfatal cases – those with at least a month of survival after hospital admission – because of insufficient data on medication use associated with fatal MIs, the report states.

Nonfatal MIs were defined as heat-related if they struck on days reaching the 95th percentile for temperature across the 14 years, in this case 24.2 °C (about 75.6 °F), relative to the average temperature of lowest nonfatal MI risk across the cohort, 7.5 °C (about 45.5 °F).

Patients served as both cases and their own controls, in that air temperature exposures on the day of their MI (case day) were compared with the remaining same days of the week in the same calendar month (control days). That approach, the report stated, “automatically controls for long-term time trends, seasonality, day of the week, and time-invariant confounders (for example, pre-existing cardiovascular disease).”

The odds ratio for heat-related MI for patients on antiplatelets was 1.63 (95% confidence interval, 1.07-2.46), and for antiplatelet nonusers was 0.94 (95% CI, 0.68-1.29). The difference between the two ratios was significant (P = .04).

The corresponding OR for patients taking beta-blockers was 1.65 (95% CI, 1.11-2.45), and for nonusers of beta-blockers was 0.90 (95% CI, 0.64-1.26). Again, the OR difference was significant (P = .02).

The ORs for users of both medication classes and nonusers of either med class, respectively, were 1.75 (95% CI, 1.12-2.73) and 0.84 (95% CI, 0.59-1.19). The latter OR was significantly lower than former (P = .01).

In a sign that antiplatelet and beta-blocker use might have been just a marker for sicker patients who were more vulnerable to heat-related MI, Chen said, the nonfatal MI risk was significantly elevated (OR, 2.17; 95% CI, 1.40-3.38) among patients with pre-existing CHD, but not among those free of pre-existing CHD (OR, 0.88; 95% CI, 0.65-1.20); the odds difference was P < .01.

That signal of confounding by indication is somewhat countered, the report states, by variations in nonfatal MI risk by age group. The increased chances of an event seen overall in relation to beta-blockers and antiplatelets were more pronounced among the 39% of patients aged 25-59 years (P < .01). That’s in spite that group’s lower CHD prevalence. The risk elevation solely among the older patients was attenuated and rendered nonsignificant, even with their greater CHD burden, the report noted.

The report speculates on a potential mechanism by which beta-blockers, at least, might conceivably raise the risk for heat-related MI. “Beta-receptor blockers inhibit skin vasodilation, resulting in reduced heat dissipation through convection and, at the same time, could intensify the blood-pressure-lowering effect of other antihypertensive drugs, which then could lead to syncope.”

Beta-blockers, Dr. Chen said, “can mechanistically make people more vulnerable to heat. That’s one potential explanation. Or it could be that these people taking the medications are just sicker. Whatever the reasons, the phenomenon we observed is that these patients taking these two medications are at higher risk during high-temperature days.”

Dr. Chen and the other authors declare no competing interests.

A version of this article first appeared on Medscape.com.

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.