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EHR alerts boosted MRA prescribing to patients with HFrEF
NEW ORLEANS – EHR-embedded alerts that a patient with heart failure with reduced ejection fraction (HFrEF) is a great candidate for treatment with a mineralocorticoid receptor antagonist (MRA) more than doubled prescribing of this “pillar” class for HFrEF, compared with control practices that used usual care and no alerts.
That’s according to results of BETTER CARE-HF, a single-center, randomized trial with more than 2,000 patients and involving 180 cardiologists.
“EHR-embedded tools cans be a rapid, low-cost, and high-impact method to increase prescription of life-saving therapies across large populations,” said Amrita Mukhopadhyay, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Her study targeted underprescribing of an MRA – spironolactone or eplerenone (Inspra) – because of its “vastly underprescribed” status in U.S. practice, where roughly two-thirds of patients with HFrEF do not receive an MRA despite clear recommendations from several medical groups that it is an essential part of treatment for most patients with HFrEF. Dr. Mukhopadhyay estimated that more comprehensive prescribing of MRAs to U.S. patients with HFrEF could prevent more than 20,000 deaths annually.
She also explained that the EHR-embedded alert was carefully devised, through interviews with cardiologists and pilot testing, to optimize the nudge so that it was less intrusive but effective for capturing attention and initiating action.
‘Clinically relevant, impressive results’
“This is a really important study, because despite overwhelming evidence for more than a decade favoring MRA use for patients with HFrEF there is an incredibly large treatment gap. MRAs can reduce all-cause death in people with HFrEF by 25%-30%, as well as reduce hospitalizations for heart failure, at a cost of less than $50 a year,” commented Gregg C. Fonarow, MD, interim chief of cardiology at the University of California, Los Angeles. The study showed “very clinically relevant, impressive results” for individualized, patient-specific alerts to prescribe an MRA and order the laboratory tests, particularly for serum potassium levels, needed to safely start the treatment, Dr. Fonarow said in an interview.
The BETTER CARE-HF study ran at more than 60 practices in the New York City region operated by the NYU Langone Health system, which sponsored the study. The trial randomized 180 cardiologists from these practices in a cluster format to one of three study arms: Sixty cardiologists received the EHR-embedded alerts for their relevant patients (755 patients) when the patient was in the physician’s office; another 60 cardiologists received a less tailored, monthly message that flagged all patients with HFrEF in a cardiologist’s practice who remained untreated candidates for MRA intervention (812 patients); and a third arm of 60 cardiologists and their HFrEF patients served as controls where the clinicians received no alert or message (644 patients).
The study included 2,211 patients with HFrEF and not on MRA treatment at baseline who were all identified as good candidates for starting treatment with the class, with no contraindications, no preexisting hyperkalemia, and no advanced-stage renal dysfunction.
The study’s primary outcome was the percentage of patients in each subgroup who received a new prescription for an MRA. This occurred in 29.6% of the patients whose physicians received an alert, in 15.6% of the patients whose physicians received a monthly message, and in 11.7% of patients in the control practices. Statistical analyses showed that the alerts led to a significant 2.53-fold increase in MRA prescribing, while the messages linked with a significant 67% increase in prescribing, compared with the control practices, reported Dr. Mukhopadhyay, a health services researcher at NYU Langone Health in New York. Simultaneously with her report, the results also appeared in the Journal of the American College of Cardiology.
The findings also showed that the alert and message had no significant impact on the prescribing of any other medication classes for HFrEF, compared with the controls. And the alert intervention had minimal adverse effects. While patients in the alert arm showed a significant, 45% relative increase in the incidence of hyperkalemia episodes, compared with control patients (because of a 4.5% absolute increase in hyperkalemia events), the rate of “significant” hyperkalemia with a value of at least 5.5 mmol/L, occurred in 5.0% of patients in the alert group and 5.1% of patients in the control arm.
Potassium testing poses another barrier
Even though the alerts substantially improved MRA prescribing, 70% of patients deemed MRA eligible in the alert subgroup still failed to receive a prescription. One additional barrier specific to MRA prescribing is the need it triggers for serial laboratory testing to monitor serum potassium levels. “Potassium testing generates additional work outside the index visit, which along with the risk for hyperkalemia exists as a barrier,” commented Lee R. Goldberg, MD, a heart failure specialist and professor at the University of Pennsylvania in Philadelphia. “This may be the next aspect to focus on to improve MRA uptake,” he said as a designated discussant for the report.
“It’s not enough to just prompt medication treatment. We also need to prompt appropriate laboratory testing,” noted Dr. Fonarow.
He also said that the approach tested by Dr. Mukhopadhyay could now be expanded to outpatient cardiologists. “The onus is on everyone involved in caring for patients with HFrEF failure to explain why maximum effort is not being made to deploy” all of the guideline-directed medical therapies for the disorder.
EHR alerts “are one way to bridge the prescribing gap, but we need multiple approaches so that all eligible patients receive guideline-directed medical therapy,” Dr. Fonarow said.
BETTER CARE-HF received no commercial funding, and Dr. Mukhopadhyay had no disclosures. Dr. Fonarow has been a consultant to AstraZeneca, Amgen, Cytokinetics, Lilly, Merck, Novartis, and Pfizer. Dr. Goldberg has received personal fees from Abbott, VisCardia, and Zoll/Respircardia.
NEW ORLEANS – EHR-embedded alerts that a patient with heart failure with reduced ejection fraction (HFrEF) is a great candidate for treatment with a mineralocorticoid receptor antagonist (MRA) more than doubled prescribing of this “pillar” class for HFrEF, compared with control practices that used usual care and no alerts.
That’s according to results of BETTER CARE-HF, a single-center, randomized trial with more than 2,000 patients and involving 180 cardiologists.
“EHR-embedded tools cans be a rapid, low-cost, and high-impact method to increase prescription of life-saving therapies across large populations,” said Amrita Mukhopadhyay, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Her study targeted underprescribing of an MRA – spironolactone or eplerenone (Inspra) – because of its “vastly underprescribed” status in U.S. practice, where roughly two-thirds of patients with HFrEF do not receive an MRA despite clear recommendations from several medical groups that it is an essential part of treatment for most patients with HFrEF. Dr. Mukhopadhyay estimated that more comprehensive prescribing of MRAs to U.S. patients with HFrEF could prevent more than 20,000 deaths annually.
She also explained that the EHR-embedded alert was carefully devised, through interviews with cardiologists and pilot testing, to optimize the nudge so that it was less intrusive but effective for capturing attention and initiating action.
‘Clinically relevant, impressive results’
“This is a really important study, because despite overwhelming evidence for more than a decade favoring MRA use for patients with HFrEF there is an incredibly large treatment gap. MRAs can reduce all-cause death in people with HFrEF by 25%-30%, as well as reduce hospitalizations for heart failure, at a cost of less than $50 a year,” commented Gregg C. Fonarow, MD, interim chief of cardiology at the University of California, Los Angeles. The study showed “very clinically relevant, impressive results” for individualized, patient-specific alerts to prescribe an MRA and order the laboratory tests, particularly for serum potassium levels, needed to safely start the treatment, Dr. Fonarow said in an interview.
The BETTER CARE-HF study ran at more than 60 practices in the New York City region operated by the NYU Langone Health system, which sponsored the study. The trial randomized 180 cardiologists from these practices in a cluster format to one of three study arms: Sixty cardiologists received the EHR-embedded alerts for their relevant patients (755 patients) when the patient was in the physician’s office; another 60 cardiologists received a less tailored, monthly message that flagged all patients with HFrEF in a cardiologist’s practice who remained untreated candidates for MRA intervention (812 patients); and a third arm of 60 cardiologists and their HFrEF patients served as controls where the clinicians received no alert or message (644 patients).
The study included 2,211 patients with HFrEF and not on MRA treatment at baseline who were all identified as good candidates for starting treatment with the class, with no contraindications, no preexisting hyperkalemia, and no advanced-stage renal dysfunction.
The study’s primary outcome was the percentage of patients in each subgroup who received a new prescription for an MRA. This occurred in 29.6% of the patients whose physicians received an alert, in 15.6% of the patients whose physicians received a monthly message, and in 11.7% of patients in the control practices. Statistical analyses showed that the alerts led to a significant 2.53-fold increase in MRA prescribing, while the messages linked with a significant 67% increase in prescribing, compared with the control practices, reported Dr. Mukhopadhyay, a health services researcher at NYU Langone Health in New York. Simultaneously with her report, the results also appeared in the Journal of the American College of Cardiology.
The findings also showed that the alert and message had no significant impact on the prescribing of any other medication classes for HFrEF, compared with the controls. And the alert intervention had minimal adverse effects. While patients in the alert arm showed a significant, 45% relative increase in the incidence of hyperkalemia episodes, compared with control patients (because of a 4.5% absolute increase in hyperkalemia events), the rate of “significant” hyperkalemia with a value of at least 5.5 mmol/L, occurred in 5.0% of patients in the alert group and 5.1% of patients in the control arm.
Potassium testing poses another barrier
Even though the alerts substantially improved MRA prescribing, 70% of patients deemed MRA eligible in the alert subgroup still failed to receive a prescription. One additional barrier specific to MRA prescribing is the need it triggers for serial laboratory testing to monitor serum potassium levels. “Potassium testing generates additional work outside the index visit, which along with the risk for hyperkalemia exists as a barrier,” commented Lee R. Goldberg, MD, a heart failure specialist and professor at the University of Pennsylvania in Philadelphia. “This may be the next aspect to focus on to improve MRA uptake,” he said as a designated discussant for the report.
“It’s not enough to just prompt medication treatment. We also need to prompt appropriate laboratory testing,” noted Dr. Fonarow.
He also said that the approach tested by Dr. Mukhopadhyay could now be expanded to outpatient cardiologists. “The onus is on everyone involved in caring for patients with HFrEF failure to explain why maximum effort is not being made to deploy” all of the guideline-directed medical therapies for the disorder.
EHR alerts “are one way to bridge the prescribing gap, but we need multiple approaches so that all eligible patients receive guideline-directed medical therapy,” Dr. Fonarow said.
BETTER CARE-HF received no commercial funding, and Dr. Mukhopadhyay had no disclosures. Dr. Fonarow has been a consultant to AstraZeneca, Amgen, Cytokinetics, Lilly, Merck, Novartis, and Pfizer. Dr. Goldberg has received personal fees from Abbott, VisCardia, and Zoll/Respircardia.
NEW ORLEANS – EHR-embedded alerts that a patient with heart failure with reduced ejection fraction (HFrEF) is a great candidate for treatment with a mineralocorticoid receptor antagonist (MRA) more than doubled prescribing of this “pillar” class for HFrEF, compared with control practices that used usual care and no alerts.
That’s according to results of BETTER CARE-HF, a single-center, randomized trial with more than 2,000 patients and involving 180 cardiologists.
“EHR-embedded tools cans be a rapid, low-cost, and high-impact method to increase prescription of life-saving therapies across large populations,” said Amrita Mukhopadhyay, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Her study targeted underprescribing of an MRA – spironolactone or eplerenone (Inspra) – because of its “vastly underprescribed” status in U.S. practice, where roughly two-thirds of patients with HFrEF do not receive an MRA despite clear recommendations from several medical groups that it is an essential part of treatment for most patients with HFrEF. Dr. Mukhopadhyay estimated that more comprehensive prescribing of MRAs to U.S. patients with HFrEF could prevent more than 20,000 deaths annually.
She also explained that the EHR-embedded alert was carefully devised, through interviews with cardiologists and pilot testing, to optimize the nudge so that it was less intrusive but effective for capturing attention and initiating action.
‘Clinically relevant, impressive results’
“This is a really important study, because despite overwhelming evidence for more than a decade favoring MRA use for patients with HFrEF there is an incredibly large treatment gap. MRAs can reduce all-cause death in people with HFrEF by 25%-30%, as well as reduce hospitalizations for heart failure, at a cost of less than $50 a year,” commented Gregg C. Fonarow, MD, interim chief of cardiology at the University of California, Los Angeles. The study showed “very clinically relevant, impressive results” for individualized, patient-specific alerts to prescribe an MRA and order the laboratory tests, particularly for serum potassium levels, needed to safely start the treatment, Dr. Fonarow said in an interview.
The BETTER CARE-HF study ran at more than 60 practices in the New York City region operated by the NYU Langone Health system, which sponsored the study. The trial randomized 180 cardiologists from these practices in a cluster format to one of three study arms: Sixty cardiologists received the EHR-embedded alerts for their relevant patients (755 patients) when the patient was in the physician’s office; another 60 cardiologists received a less tailored, monthly message that flagged all patients with HFrEF in a cardiologist’s practice who remained untreated candidates for MRA intervention (812 patients); and a third arm of 60 cardiologists and their HFrEF patients served as controls where the clinicians received no alert or message (644 patients).
The study included 2,211 patients with HFrEF and not on MRA treatment at baseline who were all identified as good candidates for starting treatment with the class, with no contraindications, no preexisting hyperkalemia, and no advanced-stage renal dysfunction.
The study’s primary outcome was the percentage of patients in each subgroup who received a new prescription for an MRA. This occurred in 29.6% of the patients whose physicians received an alert, in 15.6% of the patients whose physicians received a monthly message, and in 11.7% of patients in the control practices. Statistical analyses showed that the alerts led to a significant 2.53-fold increase in MRA prescribing, while the messages linked with a significant 67% increase in prescribing, compared with the control practices, reported Dr. Mukhopadhyay, a health services researcher at NYU Langone Health in New York. Simultaneously with her report, the results also appeared in the Journal of the American College of Cardiology.
The findings also showed that the alert and message had no significant impact on the prescribing of any other medication classes for HFrEF, compared with the controls. And the alert intervention had minimal adverse effects. While patients in the alert arm showed a significant, 45% relative increase in the incidence of hyperkalemia episodes, compared with control patients (because of a 4.5% absolute increase in hyperkalemia events), the rate of “significant” hyperkalemia with a value of at least 5.5 mmol/L, occurred in 5.0% of patients in the alert group and 5.1% of patients in the control arm.
Potassium testing poses another barrier
Even though the alerts substantially improved MRA prescribing, 70% of patients deemed MRA eligible in the alert subgroup still failed to receive a prescription. One additional barrier specific to MRA prescribing is the need it triggers for serial laboratory testing to monitor serum potassium levels. “Potassium testing generates additional work outside the index visit, which along with the risk for hyperkalemia exists as a barrier,” commented Lee R. Goldberg, MD, a heart failure specialist and professor at the University of Pennsylvania in Philadelphia. “This may be the next aspect to focus on to improve MRA uptake,” he said as a designated discussant for the report.
“It’s not enough to just prompt medication treatment. We also need to prompt appropriate laboratory testing,” noted Dr. Fonarow.
He also said that the approach tested by Dr. Mukhopadhyay could now be expanded to outpatient cardiologists. “The onus is on everyone involved in caring for patients with HFrEF failure to explain why maximum effort is not being made to deploy” all of the guideline-directed medical therapies for the disorder.
EHR alerts “are one way to bridge the prescribing gap, but we need multiple approaches so that all eligible patients receive guideline-directed medical therapy,” Dr. Fonarow said.
BETTER CARE-HF received no commercial funding, and Dr. Mukhopadhyay had no disclosures. Dr. Fonarow has been a consultant to AstraZeneca, Amgen, Cytokinetics, Lilly, Merck, Novartis, and Pfizer. Dr. Goldberg has received personal fees from Abbott, VisCardia, and Zoll/Respircardia.
AT ACC 2023
Viability-guided PCI doubted in stable severe CAD: REVIVED-BCIS2
There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.
The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.
But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).
Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).
Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.
Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..
Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”
That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”
The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.
About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.
Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.
Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.
The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).
The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).
Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.
The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.
“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”
Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”
REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.
A version of this article first appeared on Medscape.com.
There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.
The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.
But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).
Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).
Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.
Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..
Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”
That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”
The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.
About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.
Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.
Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.
The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).
The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).
Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.
The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.
“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”
Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”
REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.
A version of this article first appeared on Medscape.com.
There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.
The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.
But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).
Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).
Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.
Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..
Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”
That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”
The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.
About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.
Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.
Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.
The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).
The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).
Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.
The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.
“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”
Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”
REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.
A version of this article first appeared on Medscape.com.
FROM ACC 2023
Atorvastatin cut anthracycline cardiac dysfunction in lymphoma
NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.
“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.
“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
A basis for an ‘important discussion’ with patients
“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.
“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”
Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.
STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.
Their cumulative, median anthracycline dose was 300 mg/m2, which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.
Tripled incidence of cardiac dysfunction in placebo patients
The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.
The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.
The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.
Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.
“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
The importance of a clinically meaningful effect
The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m2, and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.
In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.
Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.
STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.
NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.
“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.
“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
A basis for an ‘important discussion’ with patients
“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.
“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”
Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.
STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.
Their cumulative, median anthracycline dose was 300 mg/m2, which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.
Tripled incidence of cardiac dysfunction in placebo patients
The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.
The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.
The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.
Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.
“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
The importance of a clinically meaningful effect
The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m2, and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.
In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.
Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.
STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.
NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.
“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.
“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
A basis for an ‘important discussion’ with patients
“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.
“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”
Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.
STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.
Their cumulative, median anthracycline dose was 300 mg/m2, which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.
Tripled incidence of cardiac dysfunction in placebo patients
The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.
The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.
The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.
Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.
“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
The importance of a clinically meaningful effect
The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m2, and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.
In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.
Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.
STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.
AT ACC 2023
Transcatheter tricuspid valve repair effective and safe for regurgitation
NEW ORLEANS – In the first pivotal randomized, controlled trial of a transcatheter device for the repair of severe tricuspid regurgitation, a large reduction in valve dysfunction was associated with substantial improvement in quality of life (QOL) persisting out of 1 year of follow-up, according to results of the TRILUMINATE trial.
Based on the low procedural risks of the repair, the principal investigator, Paul Sorajja, MD, called the results “very clinically meaningful” as he presented the results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Conducted at 65 centers in the United States, Canada, and North America, TRILUMINATE evaluated a transcatheter end-to-end (TEER) repair performed with the TriClip G4 Delivery System (Abbott). The study included two cohorts, both of which will be followed for 5 years. One included patients with very severe tricuspid regurgitation enrolled in a single arm. Data on this cohort is expected later in 2023.
In the randomized portion of the study, 350 patients enrolled with severe tricuspid regurgitation underwent TEER with a clipping device and then were followed on the guideline-directed therapy (GDMT) for heart failure they were receiving at baseline. The control group was managed on GDMT alone.
The primary composite endpoint at 1 year was a composite of death from any cause and/or tricuspid valve surgery, hospitalization for heart failure, and quality of life as measured with the Kansas City Cardiomyopathy questionnaire (KCCQ).
Benefit driven by quality of life
For the primary endpoint, the win ratio, a statistical calculation of those who did relative to those who did not benefit, was 1.48, signifying a 48% advantage (P = .02). This was driven almost entirely by the KCCQ endpoint. There was no significant difference death and/or tricuspid valve surgery, which occurred in about 10% of both groups (P = .75) or heart failure hospitalization, which was occurred in slightly more patients randomized to repair (14.9% vs. 12.1%; P = .41).
For KCCQ, the mean increase at 1 year was 12.3 points in the repair group versus 0.6 points (P < .001) in the control group. With an increase of 5-10 points typically considered to be clinically meaningful, the advantage of repair over GDMT at the threshold of 15 points or greater was highly statistically significant (49.7% vs. 26.4%; P < .0001).
This advantage was attributed to control of regurgitation. The proportion achieving moderate or less regurgitation sustained at 1 year was 87% in the repair group versus 4.8% in the GDMT group (P < .0001).
When assessed independent of treatment, KCCQ benefits at 1 year increased in a stepwise fashion as severity of regurgitation was reduced, climbing from 2 points if there was no improvement to 6 points with one grade in improvement and then to 18 points with at least a two-grade improvement.
For regurgitation, “the repair was extremely effective,” said Dr. Sorajja of Allina Health Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis. He added that the degree of regurgitation control in the TRILUMINATE trial “is the highest ever reported.” With previous trials with other transcatheter devices in development, the improvement so far has been on the order of 70%-80%.
For enrollment in TRILUMINATE, patients were required to have at least an intermediate risk of morbidity or mortality from tricuspid valve surgery. Exclusion criteria included a left ventricular ejection fraction (LVEF) less than 20% and severe pulmonary hypertension.
More than 70% of patients had the highest (torrential) or second highest (massive) category of regurgitation on a five-level scale by echocardiography. Almost all the remaining were at the third level (severe).
Of those enrolled, the average age was roughly 78 years. About 55% were women. Nearly 60% were in New York Heart Association class III or IV heart failure and most had significant comorbidities, including hypertension (> 80%), atrial fibrillation (about 90%), and renal disease (35%). Patients with diabetes (16%), chronic obstructive pulmonary disease (10%), and liver disease (7.5%) were represented in lower numbers.
Surgery is not necessarily an option
All enrolled patients were considered to be at intermediate or greater risk for mortality with surgical replacement of the tricuspid valve, but Dr. Sorajja pointed out that surgery, which involves valve replacement, is not necessarily an alternative to valve repair. Even in fit patients, the high morbidity, mortality, and extended hospital stay associated with surgical valve replacement makes this procedure unattractive.
In this trial, most patients who underwent the transcatheter procedure were discharged within a day. The safety was excellent, Dr. Sorajja said. Only three patients (1.7%) had a major adverse event. This included two cases of new-onset renal failure and one cardiovascular death. There were no cases of endocarditis requiring surgery or any other type of nonelective cardiovascular surgery, including for any device-related issue.
In the sick population enrolled, Dr. Sorajja characterized the number of adverse events over 1 year as “very low.”
These results are important, according to Kendra Grubb, MD, surgical director of the Structural Heart and Valve Center, Emory University, Atlanta. While she expressed surprise that there was no signal of benefit on hard endpoints at 1 year, she emphasized that “these patients feel terrible,” and they are frustrating to manage because surgery is often contraindicated or impractical.
“Finally, we have something for this group,” she said, noting that the mortality from valve replacement surgery even among patients who are fit enough for surgery to be considered is about 10%.
Ajay Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, was more circumspect. He agreed that the improvement in QOL was encouraging, but cautioned that QOL is a particularly soft outcome in a nonrandomized trial in which patients may feel better just knowing that there regurgitation has been controlled. He found the lack of benefit on hard outcomes not just surprising but “disappointing.”
Still, he agreed the improvement in QOL is potentially meaningful for a procedure that appears to be relatively safe.
Dr. Sorajja reported financial relationships with Boston Scientific, Edwards Lifesciences, Foldax. 4C Medical, Gore Medtronic, Phillips, Siemens, Shifamed, Vdyne, xDot, and Abbott Structural, which provided funding for this trial. Dr. Grubb reported financial relationships with Abbott Vascular, Ancora Heart, Bioventrix, Boston Scientific, Edwards Lifesciences, 4C Medical, JenaValve, and Medtronic. Dr. Kirtane reported financial relationships with Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic, Opsens, Phillips, ReCor, Regeneron, and Zoll.
NEW ORLEANS – In the first pivotal randomized, controlled trial of a transcatheter device for the repair of severe tricuspid regurgitation, a large reduction in valve dysfunction was associated with substantial improvement in quality of life (QOL) persisting out of 1 year of follow-up, according to results of the TRILUMINATE trial.
Based on the low procedural risks of the repair, the principal investigator, Paul Sorajja, MD, called the results “very clinically meaningful” as he presented the results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Conducted at 65 centers in the United States, Canada, and North America, TRILUMINATE evaluated a transcatheter end-to-end (TEER) repair performed with the TriClip G4 Delivery System (Abbott). The study included two cohorts, both of which will be followed for 5 years. One included patients with very severe tricuspid regurgitation enrolled in a single arm. Data on this cohort is expected later in 2023.
In the randomized portion of the study, 350 patients enrolled with severe tricuspid regurgitation underwent TEER with a clipping device and then were followed on the guideline-directed therapy (GDMT) for heart failure they were receiving at baseline. The control group was managed on GDMT alone.
The primary composite endpoint at 1 year was a composite of death from any cause and/or tricuspid valve surgery, hospitalization for heart failure, and quality of life as measured with the Kansas City Cardiomyopathy questionnaire (KCCQ).
Benefit driven by quality of life
For the primary endpoint, the win ratio, a statistical calculation of those who did relative to those who did not benefit, was 1.48, signifying a 48% advantage (P = .02). This was driven almost entirely by the KCCQ endpoint. There was no significant difference death and/or tricuspid valve surgery, which occurred in about 10% of both groups (P = .75) or heart failure hospitalization, which was occurred in slightly more patients randomized to repair (14.9% vs. 12.1%; P = .41).
For KCCQ, the mean increase at 1 year was 12.3 points in the repair group versus 0.6 points (P < .001) in the control group. With an increase of 5-10 points typically considered to be clinically meaningful, the advantage of repair over GDMT at the threshold of 15 points or greater was highly statistically significant (49.7% vs. 26.4%; P < .0001).
This advantage was attributed to control of regurgitation. The proportion achieving moderate or less regurgitation sustained at 1 year was 87% in the repair group versus 4.8% in the GDMT group (P < .0001).
When assessed independent of treatment, KCCQ benefits at 1 year increased in a stepwise fashion as severity of regurgitation was reduced, climbing from 2 points if there was no improvement to 6 points with one grade in improvement and then to 18 points with at least a two-grade improvement.
For regurgitation, “the repair was extremely effective,” said Dr. Sorajja of Allina Health Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis. He added that the degree of regurgitation control in the TRILUMINATE trial “is the highest ever reported.” With previous trials with other transcatheter devices in development, the improvement so far has been on the order of 70%-80%.
For enrollment in TRILUMINATE, patients were required to have at least an intermediate risk of morbidity or mortality from tricuspid valve surgery. Exclusion criteria included a left ventricular ejection fraction (LVEF) less than 20% and severe pulmonary hypertension.
More than 70% of patients had the highest (torrential) or second highest (massive) category of regurgitation on a five-level scale by echocardiography. Almost all the remaining were at the third level (severe).
Of those enrolled, the average age was roughly 78 years. About 55% were women. Nearly 60% were in New York Heart Association class III or IV heart failure and most had significant comorbidities, including hypertension (> 80%), atrial fibrillation (about 90%), and renal disease (35%). Patients with diabetes (16%), chronic obstructive pulmonary disease (10%), and liver disease (7.5%) were represented in lower numbers.
Surgery is not necessarily an option
All enrolled patients were considered to be at intermediate or greater risk for mortality with surgical replacement of the tricuspid valve, but Dr. Sorajja pointed out that surgery, which involves valve replacement, is not necessarily an alternative to valve repair. Even in fit patients, the high morbidity, mortality, and extended hospital stay associated with surgical valve replacement makes this procedure unattractive.
In this trial, most patients who underwent the transcatheter procedure were discharged within a day. The safety was excellent, Dr. Sorajja said. Only three patients (1.7%) had a major adverse event. This included two cases of new-onset renal failure and one cardiovascular death. There were no cases of endocarditis requiring surgery or any other type of nonelective cardiovascular surgery, including for any device-related issue.
In the sick population enrolled, Dr. Sorajja characterized the number of adverse events over 1 year as “very low.”
These results are important, according to Kendra Grubb, MD, surgical director of the Structural Heart and Valve Center, Emory University, Atlanta. While she expressed surprise that there was no signal of benefit on hard endpoints at 1 year, she emphasized that “these patients feel terrible,” and they are frustrating to manage because surgery is often contraindicated or impractical.
“Finally, we have something for this group,” she said, noting that the mortality from valve replacement surgery even among patients who are fit enough for surgery to be considered is about 10%.
Ajay Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, was more circumspect. He agreed that the improvement in QOL was encouraging, but cautioned that QOL is a particularly soft outcome in a nonrandomized trial in which patients may feel better just knowing that there regurgitation has been controlled. He found the lack of benefit on hard outcomes not just surprising but “disappointing.”
Still, he agreed the improvement in QOL is potentially meaningful for a procedure that appears to be relatively safe.
Dr. Sorajja reported financial relationships with Boston Scientific, Edwards Lifesciences, Foldax. 4C Medical, Gore Medtronic, Phillips, Siemens, Shifamed, Vdyne, xDot, and Abbott Structural, which provided funding for this trial. Dr. Grubb reported financial relationships with Abbott Vascular, Ancora Heart, Bioventrix, Boston Scientific, Edwards Lifesciences, 4C Medical, JenaValve, and Medtronic. Dr. Kirtane reported financial relationships with Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic, Opsens, Phillips, ReCor, Regeneron, and Zoll.
NEW ORLEANS – In the first pivotal randomized, controlled trial of a transcatheter device for the repair of severe tricuspid regurgitation, a large reduction in valve dysfunction was associated with substantial improvement in quality of life (QOL) persisting out of 1 year of follow-up, according to results of the TRILUMINATE trial.
Based on the low procedural risks of the repair, the principal investigator, Paul Sorajja, MD, called the results “very clinically meaningful” as he presented the results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Conducted at 65 centers in the United States, Canada, and North America, TRILUMINATE evaluated a transcatheter end-to-end (TEER) repair performed with the TriClip G4 Delivery System (Abbott). The study included two cohorts, both of which will be followed for 5 years. One included patients with very severe tricuspid regurgitation enrolled in a single arm. Data on this cohort is expected later in 2023.
In the randomized portion of the study, 350 patients enrolled with severe tricuspid regurgitation underwent TEER with a clipping device and then were followed on the guideline-directed therapy (GDMT) for heart failure they were receiving at baseline. The control group was managed on GDMT alone.
The primary composite endpoint at 1 year was a composite of death from any cause and/or tricuspid valve surgery, hospitalization for heart failure, and quality of life as measured with the Kansas City Cardiomyopathy questionnaire (KCCQ).
Benefit driven by quality of life
For the primary endpoint, the win ratio, a statistical calculation of those who did relative to those who did not benefit, was 1.48, signifying a 48% advantage (P = .02). This was driven almost entirely by the KCCQ endpoint. There was no significant difference death and/or tricuspid valve surgery, which occurred in about 10% of both groups (P = .75) or heart failure hospitalization, which was occurred in slightly more patients randomized to repair (14.9% vs. 12.1%; P = .41).
For KCCQ, the mean increase at 1 year was 12.3 points in the repair group versus 0.6 points (P < .001) in the control group. With an increase of 5-10 points typically considered to be clinically meaningful, the advantage of repair over GDMT at the threshold of 15 points or greater was highly statistically significant (49.7% vs. 26.4%; P < .0001).
This advantage was attributed to control of regurgitation. The proportion achieving moderate or less regurgitation sustained at 1 year was 87% in the repair group versus 4.8% in the GDMT group (P < .0001).
When assessed independent of treatment, KCCQ benefits at 1 year increased in a stepwise fashion as severity of regurgitation was reduced, climbing from 2 points if there was no improvement to 6 points with one grade in improvement and then to 18 points with at least a two-grade improvement.
For regurgitation, “the repair was extremely effective,” said Dr. Sorajja of Allina Health Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis. He added that the degree of regurgitation control in the TRILUMINATE trial “is the highest ever reported.” With previous trials with other transcatheter devices in development, the improvement so far has been on the order of 70%-80%.
For enrollment in TRILUMINATE, patients were required to have at least an intermediate risk of morbidity or mortality from tricuspid valve surgery. Exclusion criteria included a left ventricular ejection fraction (LVEF) less than 20% and severe pulmonary hypertension.
More than 70% of patients had the highest (torrential) or second highest (massive) category of regurgitation on a five-level scale by echocardiography. Almost all the remaining were at the third level (severe).
Of those enrolled, the average age was roughly 78 years. About 55% were women. Nearly 60% were in New York Heart Association class III or IV heart failure and most had significant comorbidities, including hypertension (> 80%), atrial fibrillation (about 90%), and renal disease (35%). Patients with diabetes (16%), chronic obstructive pulmonary disease (10%), and liver disease (7.5%) were represented in lower numbers.
Surgery is not necessarily an option
All enrolled patients were considered to be at intermediate or greater risk for mortality with surgical replacement of the tricuspid valve, but Dr. Sorajja pointed out that surgery, which involves valve replacement, is not necessarily an alternative to valve repair. Even in fit patients, the high morbidity, mortality, and extended hospital stay associated with surgical valve replacement makes this procedure unattractive.
In this trial, most patients who underwent the transcatheter procedure were discharged within a day. The safety was excellent, Dr. Sorajja said. Only three patients (1.7%) had a major adverse event. This included two cases of new-onset renal failure and one cardiovascular death. There were no cases of endocarditis requiring surgery or any other type of nonelective cardiovascular surgery, including for any device-related issue.
In the sick population enrolled, Dr. Sorajja characterized the number of adverse events over 1 year as “very low.”
These results are important, according to Kendra Grubb, MD, surgical director of the Structural Heart and Valve Center, Emory University, Atlanta. While she expressed surprise that there was no signal of benefit on hard endpoints at 1 year, she emphasized that “these patients feel terrible,” and they are frustrating to manage because surgery is often contraindicated or impractical.
“Finally, we have something for this group,” she said, noting that the mortality from valve replacement surgery even among patients who are fit enough for surgery to be considered is about 10%.
Ajay Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, was more circumspect. He agreed that the improvement in QOL was encouraging, but cautioned that QOL is a particularly soft outcome in a nonrandomized trial in which patients may feel better just knowing that there regurgitation has been controlled. He found the lack of benefit on hard outcomes not just surprising but “disappointing.”
Still, he agreed the improvement in QOL is potentially meaningful for a procedure that appears to be relatively safe.
Dr. Sorajja reported financial relationships with Boston Scientific, Edwards Lifesciences, Foldax. 4C Medical, Gore Medtronic, Phillips, Siemens, Shifamed, Vdyne, xDot, and Abbott Structural, which provided funding for this trial. Dr. Grubb reported financial relationships with Abbott Vascular, Ancora Heart, Bioventrix, Boston Scientific, Edwards Lifesciences, 4C Medical, JenaValve, and Medtronic. Dr. Kirtane reported financial relationships with Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic, Opsens, Phillips, ReCor, Regeneron, and Zoll.
AT ACC 2023
500 more steps a day tied to 14% lower CVD risk in older adults
Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.
“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.
The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.
The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.
Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.
Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.
Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.
The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).
In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).
Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.
However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.
Small steps may get patients started
Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.
“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.
“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.
More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”
Study fills research gap for older adults
“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.
“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.
“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.
Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.
The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.
Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.
“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.
The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.
The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.
Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.
Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.
Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.
The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).
In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).
Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.
However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.
Small steps may get patients started
Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.
“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.
“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.
More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”
Study fills research gap for older adults
“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.
“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.
“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.
Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.
The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.
Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.
“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.
The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.
The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.
Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.
Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.
Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.
The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).
In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).
Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.
However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.
Small steps may get patients started
Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.
“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.
“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.
More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”
Study fills research gap for older adults
“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.
“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.
“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.
Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.
The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.
FROM EPI/LIFESTYLE 2023
FDA declines approval for omecamtiv mecarbil in HFrEF
The Food and Drug Administration has declined to approve omecamtiv mecarbil (Cytokinetics) for treatment of adults with chronic heart failure with reduced ejection fraction (HFrEF), citing a lack of evidence on efficacy.
Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.
Last December, a panel of FDA advisers recommended against approval of omecamtiv mecarbil for chronic HFrEF, as reported by this news organization.
The FDA Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF. The drug had a PDUFA date of February 28.
The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.
As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.
This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.
In a complete response letter, the FDA said GALACTIC-HF is “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death” in adults with HFrEF, Cytokinetics shared in a news release.
Further, the FDA said results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF, with benefits that outweigh the risks, Cytokinetics said.
The company said it will request a meeting with the FDA to gain a better understanding of what may be required to support potential approval of omecamtiv mecarbil. However, the company also said it has “no plans” to conduct an additional clinical trial of omecamtiv mecarbil.
Instead, the company said its focus remains on the development of aficamten, the next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, a phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has declined to approve omecamtiv mecarbil (Cytokinetics) for treatment of adults with chronic heart failure with reduced ejection fraction (HFrEF), citing a lack of evidence on efficacy.
Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.
Last December, a panel of FDA advisers recommended against approval of omecamtiv mecarbil for chronic HFrEF, as reported by this news organization.
The FDA Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF. The drug had a PDUFA date of February 28.
The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.
As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.
This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.
In a complete response letter, the FDA said GALACTIC-HF is “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death” in adults with HFrEF, Cytokinetics shared in a news release.
Further, the FDA said results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF, with benefits that outweigh the risks, Cytokinetics said.
The company said it will request a meeting with the FDA to gain a better understanding of what may be required to support potential approval of omecamtiv mecarbil. However, the company also said it has “no plans” to conduct an additional clinical trial of omecamtiv mecarbil.
Instead, the company said its focus remains on the development of aficamten, the next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, a phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has declined to approve omecamtiv mecarbil (Cytokinetics) for treatment of adults with chronic heart failure with reduced ejection fraction (HFrEF), citing a lack of evidence on efficacy.
Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.
Last December, a panel of FDA advisers recommended against approval of omecamtiv mecarbil for chronic HFrEF, as reported by this news organization.
The FDA Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF. The drug had a PDUFA date of February 28.
The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.
As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.
This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.
In a complete response letter, the FDA said GALACTIC-HF is “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death” in adults with HFrEF, Cytokinetics shared in a news release.
Further, the FDA said results from an additional clinical trial of omecamtiv mecarbil are required to establish substantial evidence of effectiveness for the treatment of HFrEF, with benefits that outweigh the risks, Cytokinetics said.
The company said it will request a meeting with the FDA to gain a better understanding of what may be required to support potential approval of omecamtiv mecarbil. However, the company also said it has “no plans” to conduct an additional clinical trial of omecamtiv mecarbil.
Instead, the company said its focus remains on the development of aficamten, the next-in-class cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, a phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy.
A version of this article first appeared on Medscape.com.
FDA warns of potential problems with Abbott Trifecta valves
There is a potential risk of early structural valve deterioration with the Abbott Trifecta valve and Trifecta valve with glide technology (Trifecta GT), the U.S. Food and Drug Administration says in a letter to health care professionals posted on its website.
Evidence in the literature suggests a higher cumulative incidence of early structural valve deterioration (SVD) and a lower freedom from reintervention due to SVD with the Trifecta valves, compared with other commercially available bovine pericardial valves, the FDA says.
The Trifecta and Trifecta GT valves are heart valve replacement devices intended to treat diseased, damaged, or malfunctioning native or prosthetic aortic heart valves, the letter notes. The first-generation Trifecta valve was approved in 2011 but is no longer marketed in the United States. The Trifecta GT valve was approved in 2016.
Medical device reports (MDRs) received by the FDA describe early SVD with Trifecta valves, with a peak time to SVD of 3 to 4 years post-implant. “Reported outcomes include surgical valve explant/replacement, transcatheter valve-in-valve intervention, and in some cases death,” the FDA notes.
In a letter to customers, Abbott says a “complaint analysis has shown that most cases of early SVD which occur within 5 years post-implant are characterized as a non-calcific leaflet tear, while most cases of late SVD which occur beyond 5 years post-implant are characterized as a fibrous-calcific SVD.”
The FDA recommends that health care providers take the following actions:
- Be aware of the potential risk of early SVD with Trifecta valves, and current patient management considerations, as communicated by Abbott.
- Discuss the risks and benefits of all available aortic valve treatment options with patients and caregivers as part of shared clinical decision-making prior to surgery.
- Read and carefully follow the Instructions for Use when implanting a Trifecta GT valve.
- Monitor patients who have undergone implantation with Trifecta valves for signs and symptoms of potential SVD.
- Instruct patients to seek medical attention with new onset of symptoms such as shortness of breath or fatigue.
- Ensure lifelong follow-up visits, conducted at least yearly, including transthoracic echocardiogram assessment of the valve beginning 1-year post-implant.
The FDA is working with Abbott to further evaluate the issue and develop additional patient management strategies, if needed. The FDA says it will continue to monitor the literature and reports of adverse events related to the issue.
Clinicians are encouraged to report any adverse events or quality problems with the Trifecta valves to their local Abbott representative or the customer service department at 1-800-544-1664.
Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
There is a potential risk of early structural valve deterioration with the Abbott Trifecta valve and Trifecta valve with glide technology (Trifecta GT), the U.S. Food and Drug Administration says in a letter to health care professionals posted on its website.
Evidence in the literature suggests a higher cumulative incidence of early structural valve deterioration (SVD) and a lower freedom from reintervention due to SVD with the Trifecta valves, compared with other commercially available bovine pericardial valves, the FDA says.
The Trifecta and Trifecta GT valves are heart valve replacement devices intended to treat diseased, damaged, or malfunctioning native or prosthetic aortic heart valves, the letter notes. The first-generation Trifecta valve was approved in 2011 but is no longer marketed in the United States. The Trifecta GT valve was approved in 2016.
Medical device reports (MDRs) received by the FDA describe early SVD with Trifecta valves, with a peak time to SVD of 3 to 4 years post-implant. “Reported outcomes include surgical valve explant/replacement, transcatheter valve-in-valve intervention, and in some cases death,” the FDA notes.
In a letter to customers, Abbott says a “complaint analysis has shown that most cases of early SVD which occur within 5 years post-implant are characterized as a non-calcific leaflet tear, while most cases of late SVD which occur beyond 5 years post-implant are characterized as a fibrous-calcific SVD.”
The FDA recommends that health care providers take the following actions:
- Be aware of the potential risk of early SVD with Trifecta valves, and current patient management considerations, as communicated by Abbott.
- Discuss the risks and benefits of all available aortic valve treatment options with patients and caregivers as part of shared clinical decision-making prior to surgery.
- Read and carefully follow the Instructions for Use when implanting a Trifecta GT valve.
- Monitor patients who have undergone implantation with Trifecta valves for signs and symptoms of potential SVD.
- Instruct patients to seek medical attention with new onset of symptoms such as shortness of breath or fatigue.
- Ensure lifelong follow-up visits, conducted at least yearly, including transthoracic echocardiogram assessment of the valve beginning 1-year post-implant.
The FDA is working with Abbott to further evaluate the issue and develop additional patient management strategies, if needed. The FDA says it will continue to monitor the literature and reports of adverse events related to the issue.
Clinicians are encouraged to report any adverse events or quality problems with the Trifecta valves to their local Abbott representative or the customer service department at 1-800-544-1664.
Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
There is a potential risk of early structural valve deterioration with the Abbott Trifecta valve and Trifecta valve with glide technology (Trifecta GT), the U.S. Food and Drug Administration says in a letter to health care professionals posted on its website.
Evidence in the literature suggests a higher cumulative incidence of early structural valve deterioration (SVD) and a lower freedom from reintervention due to SVD with the Trifecta valves, compared with other commercially available bovine pericardial valves, the FDA says.
The Trifecta and Trifecta GT valves are heart valve replacement devices intended to treat diseased, damaged, or malfunctioning native or prosthetic aortic heart valves, the letter notes. The first-generation Trifecta valve was approved in 2011 but is no longer marketed in the United States. The Trifecta GT valve was approved in 2016.
Medical device reports (MDRs) received by the FDA describe early SVD with Trifecta valves, with a peak time to SVD of 3 to 4 years post-implant. “Reported outcomes include surgical valve explant/replacement, transcatheter valve-in-valve intervention, and in some cases death,” the FDA notes.
In a letter to customers, Abbott says a “complaint analysis has shown that most cases of early SVD which occur within 5 years post-implant are characterized as a non-calcific leaflet tear, while most cases of late SVD which occur beyond 5 years post-implant are characterized as a fibrous-calcific SVD.”
The FDA recommends that health care providers take the following actions:
- Be aware of the potential risk of early SVD with Trifecta valves, and current patient management considerations, as communicated by Abbott.
- Discuss the risks and benefits of all available aortic valve treatment options with patients and caregivers as part of shared clinical decision-making prior to surgery.
- Read and carefully follow the Instructions for Use when implanting a Trifecta GT valve.
- Monitor patients who have undergone implantation with Trifecta valves for signs and symptoms of potential SVD.
- Instruct patients to seek medical attention with new onset of symptoms such as shortness of breath or fatigue.
- Ensure lifelong follow-up visits, conducted at least yearly, including transthoracic echocardiogram assessment of the valve beginning 1-year post-implant.
The FDA is working with Abbott to further evaluate the issue and develop additional patient management strategies, if needed. The FDA says it will continue to monitor the literature and reports of adverse events related to the issue.
Clinicians are encouraged to report any adverse events or quality problems with the Trifecta valves to their local Abbott representative or the customer service department at 1-800-544-1664.
Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Fewer than 10% of eligible type 2 diabetes patients get new, pricey drugs
Fewer than 10% of American adults with type 2 diabetes who qualified for treatment with newer agents – such as an SGLT2 inhibitor or GLP-1 agonist – actually received treatment with at least one drug from drug class in 2017-2020, based on a new analysis of just over a thousand adults who participated in a representative, biannual survey and self-reported a diabetes diagnosis.
The cost of these agents, and their uncertain cost-effectiveness at current prices, is likely a key driver of the low usage rate, say the authors of a brief report published in Annals of Internal Medicine.
“Clinical studies have shown that both GLP-1 [glucagonlike peptide–1] receptor agonists and SGLT2 [sodium-glucose cotransporter 2] inhibitors yield additional clinical benefits, compared with older treatments in reducing body weight and progression of cardiovascular disease and chronic kidney disease,” write Shichao Tang, PhD, from the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues.
“However, these medications come at a substantially higher cost,” they stress.
Dr. Tang explained in an interview that the new study “points to prior studies about the high cost of these medications as a potential barrier to use, but more research is needed to understand cost-effectiveness and any potential barriers to use, including cost.”
The work “did not include research into cost-effectiveness or why the percentage of people already using these medications was low,” he emphasized.
Dr. Tang and colleagues used data collected by the U.S. National Health and Nutrition Examination Survey during two 2-year cycles between 2017 and 2020 that included 1,417 people who self-identified a diagnosis of diabetes.
Excluding those who likely had type 1 diabetes and those with incomplete data left 1,330 survey participants, including 1,133 (85%) who fit criteria for the treatment of type 2 diabetes with an agent from one of the two studied classes, as recommended in 2022 by a panel representing the American Diabetes Association and the European Association for the Study of Diabetes.
Among these 1,133 people – who represent more than 22 million American adults with type 2 diabetes who fit the 2022 criteria – a scant 3.7% were actually taking a GLP-1 agonist and 5.3% were taking an SGLT2 inhibitor.
“While it’s important to note that our data predate the 2022 recommendations, these drugs were offered as second-line therapy for patients with certain diabetes-related complications in 2017-2020” and hence provide potentially useful insights, noted Dr. Tang, a health economist with the CDC National Center for Chronic Disease Prevention and Health Promotion.
Based on retail prices listed on a United States–based website, a 30-day supply of an oral SGLT2 inhibitor can cost about $550-$600 per month, while common subcutaneously injected GLP-1 receptor agonists can run from a few hundred dollars for a daily injection or close to $1,000 for a formulation administered weekly.
“Cost-effectiveness was not formally considered in the current guideline, but an assessment of cost-effectiveness may assist better targeting of interventions to achieve the greatest effect at a sustainable cost,” the researchers conclude.
The study received no commercial funding. None of the authors had relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Fewer than 10% of American adults with type 2 diabetes who qualified for treatment with newer agents – such as an SGLT2 inhibitor or GLP-1 agonist – actually received treatment with at least one drug from drug class in 2017-2020, based on a new analysis of just over a thousand adults who participated in a representative, biannual survey and self-reported a diabetes diagnosis.
The cost of these agents, and their uncertain cost-effectiveness at current prices, is likely a key driver of the low usage rate, say the authors of a brief report published in Annals of Internal Medicine.
“Clinical studies have shown that both GLP-1 [glucagonlike peptide–1] receptor agonists and SGLT2 [sodium-glucose cotransporter 2] inhibitors yield additional clinical benefits, compared with older treatments in reducing body weight and progression of cardiovascular disease and chronic kidney disease,” write Shichao Tang, PhD, from the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues.
“However, these medications come at a substantially higher cost,” they stress.
Dr. Tang explained in an interview that the new study “points to prior studies about the high cost of these medications as a potential barrier to use, but more research is needed to understand cost-effectiveness and any potential barriers to use, including cost.”
The work “did not include research into cost-effectiveness or why the percentage of people already using these medications was low,” he emphasized.
Dr. Tang and colleagues used data collected by the U.S. National Health and Nutrition Examination Survey during two 2-year cycles between 2017 and 2020 that included 1,417 people who self-identified a diagnosis of diabetes.
Excluding those who likely had type 1 diabetes and those with incomplete data left 1,330 survey participants, including 1,133 (85%) who fit criteria for the treatment of type 2 diabetes with an agent from one of the two studied classes, as recommended in 2022 by a panel representing the American Diabetes Association and the European Association for the Study of Diabetes.
Among these 1,133 people – who represent more than 22 million American adults with type 2 diabetes who fit the 2022 criteria – a scant 3.7% were actually taking a GLP-1 agonist and 5.3% were taking an SGLT2 inhibitor.
“While it’s important to note that our data predate the 2022 recommendations, these drugs were offered as second-line therapy for patients with certain diabetes-related complications in 2017-2020” and hence provide potentially useful insights, noted Dr. Tang, a health economist with the CDC National Center for Chronic Disease Prevention and Health Promotion.
Based on retail prices listed on a United States–based website, a 30-day supply of an oral SGLT2 inhibitor can cost about $550-$600 per month, while common subcutaneously injected GLP-1 receptor agonists can run from a few hundred dollars for a daily injection or close to $1,000 for a formulation administered weekly.
“Cost-effectiveness was not formally considered in the current guideline, but an assessment of cost-effectiveness may assist better targeting of interventions to achieve the greatest effect at a sustainable cost,” the researchers conclude.
The study received no commercial funding. None of the authors had relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Fewer than 10% of American adults with type 2 diabetes who qualified for treatment with newer agents – such as an SGLT2 inhibitor or GLP-1 agonist – actually received treatment with at least one drug from drug class in 2017-2020, based on a new analysis of just over a thousand adults who participated in a representative, biannual survey and self-reported a diabetes diagnosis.
The cost of these agents, and their uncertain cost-effectiveness at current prices, is likely a key driver of the low usage rate, say the authors of a brief report published in Annals of Internal Medicine.
“Clinical studies have shown that both GLP-1 [glucagonlike peptide–1] receptor agonists and SGLT2 [sodium-glucose cotransporter 2] inhibitors yield additional clinical benefits, compared with older treatments in reducing body weight and progression of cardiovascular disease and chronic kidney disease,” write Shichao Tang, PhD, from the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues.
“However, these medications come at a substantially higher cost,” they stress.
Dr. Tang explained in an interview that the new study “points to prior studies about the high cost of these medications as a potential barrier to use, but more research is needed to understand cost-effectiveness and any potential barriers to use, including cost.”
The work “did not include research into cost-effectiveness or why the percentage of people already using these medications was low,” he emphasized.
Dr. Tang and colleagues used data collected by the U.S. National Health and Nutrition Examination Survey during two 2-year cycles between 2017 and 2020 that included 1,417 people who self-identified a diagnosis of diabetes.
Excluding those who likely had type 1 diabetes and those with incomplete data left 1,330 survey participants, including 1,133 (85%) who fit criteria for the treatment of type 2 diabetes with an agent from one of the two studied classes, as recommended in 2022 by a panel representing the American Diabetes Association and the European Association for the Study of Diabetes.
Among these 1,133 people – who represent more than 22 million American adults with type 2 diabetes who fit the 2022 criteria – a scant 3.7% were actually taking a GLP-1 agonist and 5.3% were taking an SGLT2 inhibitor.
“While it’s important to note that our data predate the 2022 recommendations, these drugs were offered as second-line therapy for patients with certain diabetes-related complications in 2017-2020” and hence provide potentially useful insights, noted Dr. Tang, a health economist with the CDC National Center for Chronic Disease Prevention and Health Promotion.
Based on retail prices listed on a United States–based website, a 30-day supply of an oral SGLT2 inhibitor can cost about $550-$600 per month, while common subcutaneously injected GLP-1 receptor agonists can run from a few hundred dollars for a daily injection or close to $1,000 for a formulation administered weekly.
“Cost-effectiveness was not formally considered in the current guideline, but an assessment of cost-effectiveness may assist better targeting of interventions to achieve the greatest effect at a sustainable cost,” the researchers conclude.
The study received no commercial funding. None of the authors had relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Cardiologists weigh in on ethically challenging issues
Would you tell a patient about a potentially harmful medical mistake? Would you upcode or overstate a patient’s condition so an insurer will cover it? What about reporting a colleague who seems impaired or engages in sexual harassment or bullying?
In a new survey, this news organization asked more than 4,100 U.S. physicians how they would react to these and other ethically challenging scenarios.
For example, a full 80% of cardiologists responding to the survey said they would reveal a potentially harmful medical mistake to their patient.
This aligns with decades of advice from major medical societies such as the American Medical Association and the American College of Physicians, which endorse disclosing to patients and families any error that could jeopardize the patient’s health.
“Disclosure of close calls should also be made. From a health law context, being upfront with the patient is standard practice,” said Eric Mathison, PhD, a clinical ethicist at University of Toronto.
When it comes to upcoding or overstating a patient’s condition so an insurer will cover it, more than three quarters of cardiologists (78%) viewed this as unacceptable, while 9% felt it was okay and 13% said “it depends.”
Many doctors are willing to stretch coding policies to the limit to support patients and their finances, said Arthur L. Caplan, PhD, NYU professor of bioethics and Medscape blogger. “That’s acceptable advocacy. But most doctors will not say they are willing to commit fraud.”
Okay to breach patient confidentiality?
More than half of cardiologists felt it was okay to breach patient confidentiality when someone’s health could be threatened, 14% felt the opposite, and 29% said it depends.
“I teach that if you know someone faces a direct risk from catching a deadly disease, and you know who that person is, then you have a duty to warn,” Dr. Caplan said. “The disease has to be serious for [breaching confidentiality] to be morally defensible, and your disclosure has to be actionable. Telling your mother won’t achieve a lot” in protecting someone’s health.
In a 2020 ethics survey by this news organization, 72% of cardiologists felt that they could accept a meal or speaking gig from a drug company without its creating any issue for them.
Three years later, only 66% of cardiologists said they could accept a meal or speaking engagement without its influencing their prescribing habits; 21% said they couldn’t and 13% said it depends.
Dr. Caplan thinks that many doctors are deceiving themselves. “We know from business school case studies that even little gifts like calendars and flashlights work. Humans get a sense of debt when they receive gifts. Physicians are no exception. If you get a meal or an invitation to do a talk for a small fee, you may still say, ‘This is nothing to me,’ ” but subconscious favoritism can result, he cautioned.
Support for physician-assisted dying?
Ten states and the District of Columbia now allow physicians to help a terminally ill patient with dying. Fifty percent of cardiologists surveyed support it, 36% are against it, and 14% said it depends. These percentages are roughly the same as in 2020.
Dr. Mathison said the public and physicians are “getting more comfortable with physician-assisted dying. Physicians are seeing it used in practice and hearing from other physicians who are participating.”
However, only 31% of cardiologists felt physician-assisted dying should be allowed for patients in intractable pain; 42% said it should not be legal in this case, and 26% said it depends.
As opposed to physician-assisted dying for terminally ill patients, no U.S. state recognizes the legal right to help end the life of a patient in unending pain. However, Belgium, the Netherlands, and Luxembourg do under certain conditions.
Going public about issues with a cardiologist’s hospital or health care organization became a major issue during the COVID-19 pandemic as some medical professionals struggled to get enough personal protective equipment and made it known.
More than half of cardiologists surveyed (53%) endorsed speaking out if employers don’t provide needed resources; 9% didn’t feel this was appropriate, and 28% said it depends.
Dr. Caplan noted that prominent cases of hospitals firing nurses and doctors who complained over social media may influence cardiologists’ willingness. He also thinks some doctors would ask, “Speak out to whom?” Many cardiologists will aggressively push for resources through the internal chain of command “but don’t think talking to the media is ethical or appropriate.”
The vast majority of cardiologists and physicians overall said they have never failed to report or investigate suspected domestic abuse of a patient.
Both male and female physicians strongly support reporting of abuse cases, said Thomas May, PhD, a bioethicist at Washington State University, Spokane.
This reflects the “tremendous strides society has made in recognizing the impact of abuse and the need for required-reporting policies, because victims are often, if not usually, reticent to come forward. Required reporting is necessary and in the patient’s interests,” Dr. May said.
Romancing a patient?
More than half (58%) of cardiologists felt that having a romantic relationship with a current patient is not okay; 3% were okay with it, and 30% felt it would be okay at least 6 months after the patient-doctor relationship ended.
Dr. May said a romantic relationship is “inappropriate while the professional relationship is active and even for some time afterward. There’s a professional dynamic that needs to be maintained, a sense of objectivity.
“Plus, the physician is in a power relationship to the patient where there’s a sense of gratefulness or vulnerability that makes the patient unable to say no to a personal relationship,” Dr. May said.
Dr. May is not sure 6 months after they stop being your patient is long enough. “I’d think something like 2 years as a minimum. If I were your oncologist and helped save your life, it may never be appropriate,” Dr. May said.
In other ethical questions, one-quarter of cardiologists would report a doctor who seems impaired by drugs, alcohol, or illness, and 62% would do so only after speaking to him/her first.
“Our obligation is to do no harm to patients, and the professional standards and integrity of the profession are at stake,” one survey respondent said.
Another said, “A colleague who recognizes the problem and after private discussion enters a treatment program is often better served than by the often excessively harsh management by the state medical board.”
But when it comes to random alcohol and drug tests for cardiologists, 51% are not in favor, 31% are in favor, and 18% said it depends.
Dr. Caplan thinks that physicians face enough responsibility to patients to warrant such testing randomly but infrequently. “Doctors may feel like they’re being treated unprofessionally, like drug addicts, or question the accuracy of testing,” he noted. But he tilts instead toward “the moral fight to protect patient safety and trying to drive down malpractice costs.”
When it comes to reporting a colleague for sexual harassment or bullying, 71% of cardiologists said yes, they would report such behavior; only 7% would not, while 22% said it depends.
“If we ignore bad behavior such as this by our colleagues, then we are hurting our profession,” one physician said.
A version of this article originally appeared on Medscape.com.
Would you tell a patient about a potentially harmful medical mistake? Would you upcode or overstate a patient’s condition so an insurer will cover it? What about reporting a colleague who seems impaired or engages in sexual harassment or bullying?
In a new survey, this news organization asked more than 4,100 U.S. physicians how they would react to these and other ethically challenging scenarios.
For example, a full 80% of cardiologists responding to the survey said they would reveal a potentially harmful medical mistake to their patient.
This aligns with decades of advice from major medical societies such as the American Medical Association and the American College of Physicians, which endorse disclosing to patients and families any error that could jeopardize the patient’s health.
“Disclosure of close calls should also be made. From a health law context, being upfront with the patient is standard practice,” said Eric Mathison, PhD, a clinical ethicist at University of Toronto.
When it comes to upcoding or overstating a patient’s condition so an insurer will cover it, more than three quarters of cardiologists (78%) viewed this as unacceptable, while 9% felt it was okay and 13% said “it depends.”
Many doctors are willing to stretch coding policies to the limit to support patients and their finances, said Arthur L. Caplan, PhD, NYU professor of bioethics and Medscape blogger. “That’s acceptable advocacy. But most doctors will not say they are willing to commit fraud.”
Okay to breach patient confidentiality?
More than half of cardiologists felt it was okay to breach patient confidentiality when someone’s health could be threatened, 14% felt the opposite, and 29% said it depends.
“I teach that if you know someone faces a direct risk from catching a deadly disease, and you know who that person is, then you have a duty to warn,” Dr. Caplan said. “The disease has to be serious for [breaching confidentiality] to be morally defensible, and your disclosure has to be actionable. Telling your mother won’t achieve a lot” in protecting someone’s health.
In a 2020 ethics survey by this news organization, 72% of cardiologists felt that they could accept a meal or speaking gig from a drug company without its creating any issue for them.
Three years later, only 66% of cardiologists said they could accept a meal or speaking engagement without its influencing their prescribing habits; 21% said they couldn’t and 13% said it depends.
Dr. Caplan thinks that many doctors are deceiving themselves. “We know from business school case studies that even little gifts like calendars and flashlights work. Humans get a sense of debt when they receive gifts. Physicians are no exception. If you get a meal or an invitation to do a talk for a small fee, you may still say, ‘This is nothing to me,’ ” but subconscious favoritism can result, he cautioned.
Support for physician-assisted dying?
Ten states and the District of Columbia now allow physicians to help a terminally ill patient with dying. Fifty percent of cardiologists surveyed support it, 36% are against it, and 14% said it depends. These percentages are roughly the same as in 2020.
Dr. Mathison said the public and physicians are “getting more comfortable with physician-assisted dying. Physicians are seeing it used in practice and hearing from other physicians who are participating.”
However, only 31% of cardiologists felt physician-assisted dying should be allowed for patients in intractable pain; 42% said it should not be legal in this case, and 26% said it depends.
As opposed to physician-assisted dying for terminally ill patients, no U.S. state recognizes the legal right to help end the life of a patient in unending pain. However, Belgium, the Netherlands, and Luxembourg do under certain conditions.
Going public about issues with a cardiologist’s hospital or health care organization became a major issue during the COVID-19 pandemic as some medical professionals struggled to get enough personal protective equipment and made it known.
More than half of cardiologists surveyed (53%) endorsed speaking out if employers don’t provide needed resources; 9% didn’t feel this was appropriate, and 28% said it depends.
Dr. Caplan noted that prominent cases of hospitals firing nurses and doctors who complained over social media may influence cardiologists’ willingness. He also thinks some doctors would ask, “Speak out to whom?” Many cardiologists will aggressively push for resources through the internal chain of command “but don’t think talking to the media is ethical or appropriate.”
The vast majority of cardiologists and physicians overall said they have never failed to report or investigate suspected domestic abuse of a patient.
Both male and female physicians strongly support reporting of abuse cases, said Thomas May, PhD, a bioethicist at Washington State University, Spokane.
This reflects the “tremendous strides society has made in recognizing the impact of abuse and the need for required-reporting policies, because victims are often, if not usually, reticent to come forward. Required reporting is necessary and in the patient’s interests,” Dr. May said.
Romancing a patient?
More than half (58%) of cardiologists felt that having a romantic relationship with a current patient is not okay; 3% were okay with it, and 30% felt it would be okay at least 6 months after the patient-doctor relationship ended.
Dr. May said a romantic relationship is “inappropriate while the professional relationship is active and even for some time afterward. There’s a professional dynamic that needs to be maintained, a sense of objectivity.
“Plus, the physician is in a power relationship to the patient where there’s a sense of gratefulness or vulnerability that makes the patient unable to say no to a personal relationship,” Dr. May said.
Dr. May is not sure 6 months after they stop being your patient is long enough. “I’d think something like 2 years as a minimum. If I were your oncologist and helped save your life, it may never be appropriate,” Dr. May said.
In other ethical questions, one-quarter of cardiologists would report a doctor who seems impaired by drugs, alcohol, or illness, and 62% would do so only after speaking to him/her first.
“Our obligation is to do no harm to patients, and the professional standards and integrity of the profession are at stake,” one survey respondent said.
Another said, “A colleague who recognizes the problem and after private discussion enters a treatment program is often better served than by the often excessively harsh management by the state medical board.”
But when it comes to random alcohol and drug tests for cardiologists, 51% are not in favor, 31% are in favor, and 18% said it depends.
Dr. Caplan thinks that physicians face enough responsibility to patients to warrant such testing randomly but infrequently. “Doctors may feel like they’re being treated unprofessionally, like drug addicts, or question the accuracy of testing,” he noted. But he tilts instead toward “the moral fight to protect patient safety and trying to drive down malpractice costs.”
When it comes to reporting a colleague for sexual harassment or bullying, 71% of cardiologists said yes, they would report such behavior; only 7% would not, while 22% said it depends.
“If we ignore bad behavior such as this by our colleagues, then we are hurting our profession,” one physician said.
A version of this article originally appeared on Medscape.com.
Would you tell a patient about a potentially harmful medical mistake? Would you upcode or overstate a patient’s condition so an insurer will cover it? What about reporting a colleague who seems impaired or engages in sexual harassment or bullying?
In a new survey, this news organization asked more than 4,100 U.S. physicians how they would react to these and other ethically challenging scenarios.
For example, a full 80% of cardiologists responding to the survey said they would reveal a potentially harmful medical mistake to their patient.
This aligns with decades of advice from major medical societies such as the American Medical Association and the American College of Physicians, which endorse disclosing to patients and families any error that could jeopardize the patient’s health.
“Disclosure of close calls should also be made. From a health law context, being upfront with the patient is standard practice,” said Eric Mathison, PhD, a clinical ethicist at University of Toronto.
When it comes to upcoding or overstating a patient’s condition so an insurer will cover it, more than three quarters of cardiologists (78%) viewed this as unacceptable, while 9% felt it was okay and 13% said “it depends.”
Many doctors are willing to stretch coding policies to the limit to support patients and their finances, said Arthur L. Caplan, PhD, NYU professor of bioethics and Medscape blogger. “That’s acceptable advocacy. But most doctors will not say they are willing to commit fraud.”
Okay to breach patient confidentiality?
More than half of cardiologists felt it was okay to breach patient confidentiality when someone’s health could be threatened, 14% felt the opposite, and 29% said it depends.
“I teach that if you know someone faces a direct risk from catching a deadly disease, and you know who that person is, then you have a duty to warn,” Dr. Caplan said. “The disease has to be serious for [breaching confidentiality] to be morally defensible, and your disclosure has to be actionable. Telling your mother won’t achieve a lot” in protecting someone’s health.
In a 2020 ethics survey by this news organization, 72% of cardiologists felt that they could accept a meal or speaking gig from a drug company without its creating any issue for them.
Three years later, only 66% of cardiologists said they could accept a meal or speaking engagement without its influencing their prescribing habits; 21% said they couldn’t and 13% said it depends.
Dr. Caplan thinks that many doctors are deceiving themselves. “We know from business school case studies that even little gifts like calendars and flashlights work. Humans get a sense of debt when they receive gifts. Physicians are no exception. If you get a meal or an invitation to do a talk for a small fee, you may still say, ‘This is nothing to me,’ ” but subconscious favoritism can result, he cautioned.
Support for physician-assisted dying?
Ten states and the District of Columbia now allow physicians to help a terminally ill patient with dying. Fifty percent of cardiologists surveyed support it, 36% are against it, and 14% said it depends. These percentages are roughly the same as in 2020.
Dr. Mathison said the public and physicians are “getting more comfortable with physician-assisted dying. Physicians are seeing it used in practice and hearing from other physicians who are participating.”
However, only 31% of cardiologists felt physician-assisted dying should be allowed for patients in intractable pain; 42% said it should not be legal in this case, and 26% said it depends.
As opposed to physician-assisted dying for terminally ill patients, no U.S. state recognizes the legal right to help end the life of a patient in unending pain. However, Belgium, the Netherlands, and Luxembourg do under certain conditions.
Going public about issues with a cardiologist’s hospital or health care organization became a major issue during the COVID-19 pandemic as some medical professionals struggled to get enough personal protective equipment and made it known.
More than half of cardiologists surveyed (53%) endorsed speaking out if employers don’t provide needed resources; 9% didn’t feel this was appropriate, and 28% said it depends.
Dr. Caplan noted that prominent cases of hospitals firing nurses and doctors who complained over social media may influence cardiologists’ willingness. He also thinks some doctors would ask, “Speak out to whom?” Many cardiologists will aggressively push for resources through the internal chain of command “but don’t think talking to the media is ethical or appropriate.”
The vast majority of cardiologists and physicians overall said they have never failed to report or investigate suspected domestic abuse of a patient.
Both male and female physicians strongly support reporting of abuse cases, said Thomas May, PhD, a bioethicist at Washington State University, Spokane.
This reflects the “tremendous strides society has made in recognizing the impact of abuse and the need for required-reporting policies, because victims are often, if not usually, reticent to come forward. Required reporting is necessary and in the patient’s interests,” Dr. May said.
Romancing a patient?
More than half (58%) of cardiologists felt that having a romantic relationship with a current patient is not okay; 3% were okay with it, and 30% felt it would be okay at least 6 months after the patient-doctor relationship ended.
Dr. May said a romantic relationship is “inappropriate while the professional relationship is active and even for some time afterward. There’s a professional dynamic that needs to be maintained, a sense of objectivity.
“Plus, the physician is in a power relationship to the patient where there’s a sense of gratefulness or vulnerability that makes the patient unable to say no to a personal relationship,” Dr. May said.
Dr. May is not sure 6 months after they stop being your patient is long enough. “I’d think something like 2 years as a minimum. If I were your oncologist and helped save your life, it may never be appropriate,” Dr. May said.
In other ethical questions, one-quarter of cardiologists would report a doctor who seems impaired by drugs, alcohol, or illness, and 62% would do so only after speaking to him/her first.
“Our obligation is to do no harm to patients, and the professional standards and integrity of the profession are at stake,” one survey respondent said.
Another said, “A colleague who recognizes the problem and after private discussion enters a treatment program is often better served than by the often excessively harsh management by the state medical board.”
But when it comes to random alcohol and drug tests for cardiologists, 51% are not in favor, 31% are in favor, and 18% said it depends.
Dr. Caplan thinks that physicians face enough responsibility to patients to warrant such testing randomly but infrequently. “Doctors may feel like they’re being treated unprofessionally, like drug addicts, or question the accuracy of testing,” he noted. But he tilts instead toward “the moral fight to protect patient safety and trying to drive down malpractice costs.”
When it comes to reporting a colleague for sexual harassment or bullying, 71% of cardiologists said yes, they would report such behavior; only 7% would not, while 22% said it depends.
“If we ignore bad behavior such as this by our colleagues, then we are hurting our profession,” one physician said.
A version of this article originally appeared on Medscape.com.
Uptick in natriuretic peptides with long-term serial testing predicts new heart failure
A jump in natriuretic peptide levels over several years in middle-aged adults points to worsened long-term risks for incident heart failure (HF) and death. But their predicted long-term survival improves if serial testing shows a drop in those levels, suggests a new analysis based on a well-known longitudinal study cohort.
The findings support the risk-stratification potential of serial natriuretic peptide testing, which may improve on individual assays for predicting future HF. Such serial assays might also be useful for guiding therapy aimed at preventing, for example, progression to clinical HF, researchers speculate on the basis of the current study,
The analysis of almost 1,000 members of the ARIC (Atherosclerosis Risk in Community) cohort had been free of clinical HF at the first of two NT-proBNP assays, which were performed 6 years apart. Their 20-year clinical risk was linked to the trajectory of NT-proBNP levels across the two earlier assays.
For example, adjusted risk of incident HF more than doubled for participants with NT-proBNP levels exceeding 125 pg/mL on both assays, compared with levels that stayed under the cut point at both assays. Their mortality risk climbed by about two-thirds.
Risk for incident HF and of death climbed 86% and 32%, respectively, if NT-proBNP levels rose over the 6 years from less than to greater than 125 pg/mL. But long-term survival improved if serial assays showed a drop from the higher to the lower level.
Rising NT-proBNP levels over several years probably reflect ongoing exposure to risk factors such as hypertension or diabetes. Conversely, decreasing NT-proBNP levels likely reflect some success at keeping such risk factors under control, propose the authors of the analysis published in JAMA Cardiology. The study was led by Xiaoming Jia, MD, Baylor College of Medicine, Houston.
The findings raise the possibility that reducing NT-proBNP levels through risk-factor modification, tracked by serial assays, may potentially improve long-term risk for death or incident HF.
Such therapy, guided by natriuretic peptides, might prove especially useful in asymptomatic adults with modifiable HF risk factors but without known NT-proBNP elevation or cardiac structural changes, so-called stage A HF, senior author Vijay Nambi, MD, PhD, also of Baylor, observed for this news organization.
The best populations for serial NT-proBNP assays to guide therapy, Dr. Nambi said, should become clear “as more data emerges.” But the threshold for ordering such tests would probably be lower for people in stage A whose rising NT-proBNP levels later reclassify them as stage B, also called pre-HF.
In such cases, he speculated, intensified therapy of HF risk factors such as uncontrolled hypertension or diabetes – prompted by greater NT-proBNP levels at serial testing – might possibly avert progression to clinical HF.
“These investigators have nicely demonstrated that one measurement of the biomarker may not be sufficient, that maybe it undercaptures the true burden of people who eventually will develop heart failure,” Muthiah Vaduganathan, MD, MPH, told this news organization.
The study raises the possibility “that the serial natriuretic peptide strategy may be more efficient and more comprehensive in identifying those who will eventually progress,” said Dr. Vaduganathan, of Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not associated with the ARIC analysis.
An open question, he added, is whether the predicted risk is modifiable. “If you are able to provide the biomarker information to treating clinicians, can they do something to attenuate the risk?”
The outlook is hopeful, given contemporary therapies “that can slow and even prevent heart failure in at-risk populations,” Dr. Vaduganathan said. For example, “The selective allocation of SGLT2 inhibitors to those with elevated natriuretic peptide levels, perhaps as captured in serial measurements, would be of great interest.”
The analysis included 9,776 adults (56.5% women, 21.3% Black) without HF who underwent NT-proBNP testing at the second and – about 6 years later – the fourth scheduled clinical visits in the ARIC study, which had enrolled persons aged 45-64 from four diverse communities from across the United States.
Adjusted hazard ratios for incident HF according to NT-proBNP changes from the first to second assays relative to 125 pg/mL were as follows:
- 1.86 (95% confidence interval, 1.60-2.16) when levels rose to higher than the cut point.
- 2.40 (95% CI, 2.00-2.88) when both levels exceeded the cut point.
The corresponding adjusted HRs for death from any cause were as follows:
- 1.32 (95%CI, 1.19-1.47) when levels rose to higher than 125 mg/mL.
- 1.68 (95% CI, 1.47-1.91) when both levels were above the cut point.
The risks for incident HF and for death rose significantly by 6% and 5%, respectively, per standard deviation NT-proBNP increase from the first to second assay.
Risks for HF and mortality for participants whose NT-proBNP levels declined from greater than to less than 125 pg/mL were similar to those whose levels remained low at both assays.
Cost-effectiveness would be another issue when implementing a strategy that calls for multiple biomarker assays, Dr. Vaduganathan observed.
“Surely, we would want to demonstrate that the laboratory measurement costs are offset by downstream prevention of heart failure events that could be averted by use of effective medical therapy, such SGLT2 inhibitors.”
ARIC has been funded by the National Institutes of Health and Department of Health and Human Services. Dr. Nambi discloses receiving grants from the National Institutes of Health during the conduct of the study; support from Amgen; and stocks from Abbott Laboratories. Disclosures for the other authors are in the report. Dr. Vaduganathan has disclosed receiving grants or serving on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; speaking for AstraZeneca, Novartis, and Roche Diagnostics; and serving on trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics.
A version of this article originally appeared on Medscape.com.
A jump in natriuretic peptide levels over several years in middle-aged adults points to worsened long-term risks for incident heart failure (HF) and death. But their predicted long-term survival improves if serial testing shows a drop in those levels, suggests a new analysis based on a well-known longitudinal study cohort.
The findings support the risk-stratification potential of serial natriuretic peptide testing, which may improve on individual assays for predicting future HF. Such serial assays might also be useful for guiding therapy aimed at preventing, for example, progression to clinical HF, researchers speculate on the basis of the current study,
The analysis of almost 1,000 members of the ARIC (Atherosclerosis Risk in Community) cohort had been free of clinical HF at the first of two NT-proBNP assays, which were performed 6 years apart. Their 20-year clinical risk was linked to the trajectory of NT-proBNP levels across the two earlier assays.
For example, adjusted risk of incident HF more than doubled for participants with NT-proBNP levels exceeding 125 pg/mL on both assays, compared with levels that stayed under the cut point at both assays. Their mortality risk climbed by about two-thirds.
Risk for incident HF and of death climbed 86% and 32%, respectively, if NT-proBNP levels rose over the 6 years from less than to greater than 125 pg/mL. But long-term survival improved if serial assays showed a drop from the higher to the lower level.
Rising NT-proBNP levels over several years probably reflect ongoing exposure to risk factors such as hypertension or diabetes. Conversely, decreasing NT-proBNP levels likely reflect some success at keeping such risk factors under control, propose the authors of the analysis published in JAMA Cardiology. The study was led by Xiaoming Jia, MD, Baylor College of Medicine, Houston.
The findings raise the possibility that reducing NT-proBNP levels through risk-factor modification, tracked by serial assays, may potentially improve long-term risk for death or incident HF.
Such therapy, guided by natriuretic peptides, might prove especially useful in asymptomatic adults with modifiable HF risk factors but without known NT-proBNP elevation or cardiac structural changes, so-called stage A HF, senior author Vijay Nambi, MD, PhD, also of Baylor, observed for this news organization.
The best populations for serial NT-proBNP assays to guide therapy, Dr. Nambi said, should become clear “as more data emerges.” But the threshold for ordering such tests would probably be lower for people in stage A whose rising NT-proBNP levels later reclassify them as stage B, also called pre-HF.
In such cases, he speculated, intensified therapy of HF risk factors such as uncontrolled hypertension or diabetes – prompted by greater NT-proBNP levels at serial testing – might possibly avert progression to clinical HF.
“These investigators have nicely demonstrated that one measurement of the biomarker may not be sufficient, that maybe it undercaptures the true burden of people who eventually will develop heart failure,” Muthiah Vaduganathan, MD, MPH, told this news organization.
The study raises the possibility “that the serial natriuretic peptide strategy may be more efficient and more comprehensive in identifying those who will eventually progress,” said Dr. Vaduganathan, of Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not associated with the ARIC analysis.
An open question, he added, is whether the predicted risk is modifiable. “If you are able to provide the biomarker information to treating clinicians, can they do something to attenuate the risk?”
The outlook is hopeful, given contemporary therapies “that can slow and even prevent heart failure in at-risk populations,” Dr. Vaduganathan said. For example, “The selective allocation of SGLT2 inhibitors to those with elevated natriuretic peptide levels, perhaps as captured in serial measurements, would be of great interest.”
The analysis included 9,776 adults (56.5% women, 21.3% Black) without HF who underwent NT-proBNP testing at the second and – about 6 years later – the fourth scheduled clinical visits in the ARIC study, which had enrolled persons aged 45-64 from four diverse communities from across the United States.
Adjusted hazard ratios for incident HF according to NT-proBNP changes from the first to second assays relative to 125 pg/mL were as follows:
- 1.86 (95% confidence interval, 1.60-2.16) when levels rose to higher than the cut point.
- 2.40 (95% CI, 2.00-2.88) when both levels exceeded the cut point.
The corresponding adjusted HRs for death from any cause were as follows:
- 1.32 (95%CI, 1.19-1.47) when levels rose to higher than 125 mg/mL.
- 1.68 (95% CI, 1.47-1.91) when both levels were above the cut point.
The risks for incident HF and for death rose significantly by 6% and 5%, respectively, per standard deviation NT-proBNP increase from the first to second assay.
Risks for HF and mortality for participants whose NT-proBNP levels declined from greater than to less than 125 pg/mL were similar to those whose levels remained low at both assays.
Cost-effectiveness would be another issue when implementing a strategy that calls for multiple biomarker assays, Dr. Vaduganathan observed.
“Surely, we would want to demonstrate that the laboratory measurement costs are offset by downstream prevention of heart failure events that could be averted by use of effective medical therapy, such SGLT2 inhibitors.”
ARIC has been funded by the National Institutes of Health and Department of Health and Human Services. Dr. Nambi discloses receiving grants from the National Institutes of Health during the conduct of the study; support from Amgen; and stocks from Abbott Laboratories. Disclosures for the other authors are in the report. Dr. Vaduganathan has disclosed receiving grants or serving on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; speaking for AstraZeneca, Novartis, and Roche Diagnostics; and serving on trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics.
A version of this article originally appeared on Medscape.com.
A jump in natriuretic peptide levels over several years in middle-aged adults points to worsened long-term risks for incident heart failure (HF) and death. But their predicted long-term survival improves if serial testing shows a drop in those levels, suggests a new analysis based on a well-known longitudinal study cohort.
The findings support the risk-stratification potential of serial natriuretic peptide testing, which may improve on individual assays for predicting future HF. Such serial assays might also be useful for guiding therapy aimed at preventing, for example, progression to clinical HF, researchers speculate on the basis of the current study,
The analysis of almost 1,000 members of the ARIC (Atherosclerosis Risk in Community) cohort had been free of clinical HF at the first of two NT-proBNP assays, which were performed 6 years apart. Their 20-year clinical risk was linked to the trajectory of NT-proBNP levels across the two earlier assays.
For example, adjusted risk of incident HF more than doubled for participants with NT-proBNP levels exceeding 125 pg/mL on both assays, compared with levels that stayed under the cut point at both assays. Their mortality risk climbed by about two-thirds.
Risk for incident HF and of death climbed 86% and 32%, respectively, if NT-proBNP levels rose over the 6 years from less than to greater than 125 pg/mL. But long-term survival improved if serial assays showed a drop from the higher to the lower level.
Rising NT-proBNP levels over several years probably reflect ongoing exposure to risk factors such as hypertension or diabetes. Conversely, decreasing NT-proBNP levels likely reflect some success at keeping such risk factors under control, propose the authors of the analysis published in JAMA Cardiology. The study was led by Xiaoming Jia, MD, Baylor College of Medicine, Houston.
The findings raise the possibility that reducing NT-proBNP levels through risk-factor modification, tracked by serial assays, may potentially improve long-term risk for death or incident HF.
Such therapy, guided by natriuretic peptides, might prove especially useful in asymptomatic adults with modifiable HF risk factors but without known NT-proBNP elevation or cardiac structural changes, so-called stage A HF, senior author Vijay Nambi, MD, PhD, also of Baylor, observed for this news organization.
The best populations for serial NT-proBNP assays to guide therapy, Dr. Nambi said, should become clear “as more data emerges.” But the threshold for ordering such tests would probably be lower for people in stage A whose rising NT-proBNP levels later reclassify them as stage B, also called pre-HF.
In such cases, he speculated, intensified therapy of HF risk factors such as uncontrolled hypertension or diabetes – prompted by greater NT-proBNP levels at serial testing – might possibly avert progression to clinical HF.
“These investigators have nicely demonstrated that one measurement of the biomarker may not be sufficient, that maybe it undercaptures the true burden of people who eventually will develop heart failure,” Muthiah Vaduganathan, MD, MPH, told this news organization.
The study raises the possibility “that the serial natriuretic peptide strategy may be more efficient and more comprehensive in identifying those who will eventually progress,” said Dr. Vaduganathan, of Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not associated with the ARIC analysis.
An open question, he added, is whether the predicted risk is modifiable. “If you are able to provide the biomarker information to treating clinicians, can they do something to attenuate the risk?”
The outlook is hopeful, given contemporary therapies “that can slow and even prevent heart failure in at-risk populations,” Dr. Vaduganathan said. For example, “The selective allocation of SGLT2 inhibitors to those with elevated natriuretic peptide levels, perhaps as captured in serial measurements, would be of great interest.”
The analysis included 9,776 adults (56.5% women, 21.3% Black) without HF who underwent NT-proBNP testing at the second and – about 6 years later – the fourth scheduled clinical visits in the ARIC study, which had enrolled persons aged 45-64 from four diverse communities from across the United States.
Adjusted hazard ratios for incident HF according to NT-proBNP changes from the first to second assays relative to 125 pg/mL were as follows:
- 1.86 (95% confidence interval, 1.60-2.16) when levels rose to higher than the cut point.
- 2.40 (95% CI, 2.00-2.88) when both levels exceeded the cut point.
The corresponding adjusted HRs for death from any cause were as follows:
- 1.32 (95%CI, 1.19-1.47) when levels rose to higher than 125 mg/mL.
- 1.68 (95% CI, 1.47-1.91) when both levels were above the cut point.
The risks for incident HF and for death rose significantly by 6% and 5%, respectively, per standard deviation NT-proBNP increase from the first to second assay.
Risks for HF and mortality for participants whose NT-proBNP levels declined from greater than to less than 125 pg/mL were similar to those whose levels remained low at both assays.
Cost-effectiveness would be another issue when implementing a strategy that calls for multiple biomarker assays, Dr. Vaduganathan observed.
“Surely, we would want to demonstrate that the laboratory measurement costs are offset by downstream prevention of heart failure events that could be averted by use of effective medical therapy, such SGLT2 inhibitors.”
ARIC has been funded by the National Institutes of Health and Department of Health and Human Services. Dr. Nambi discloses receiving grants from the National Institutes of Health during the conduct of the study; support from Amgen; and stocks from Abbott Laboratories. Disclosures for the other authors are in the report. Dr. Vaduganathan has disclosed receiving grants or serving on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; speaking for AstraZeneca, Novartis, and Roche Diagnostics; and serving on trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics.
A version of this article originally appeared on Medscape.com.
FROM JAMA CARDIOLOGY