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Late-Breaking Science preview: Wednesday, Nov. 15
The final Late-Breaking Science session delves into innovative therapies and novel applications, including two phase 1-2 stem cell trials, an early trial in toxin treatments to prevent atrial fibrillation, a phase 1 test of an interatrial shunt device for heart failure with preserved ejection fraction, and more:
- TNT-POAF: Nathan Waldron, MD, of Duke University, Durham, N.C., will present results of a trial aiming to prevent postoperative atrial fibrillation with the use of temporary toxin treatment.
- REDUCE LAP–HF 1: In what the investigators call the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF, an inter-atrial shunt device designed to provide continuous and dynamic decompression of the left atrium. Sanjiv J Shah, MD, of Northwestern University will present the study, which holds the hypothesis that the device may reduce symptoms and slow the progression of heart failure.
- PROPEL: This study tested the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with supervised treadmill exercise in patients with peripheral artery disease would significantly improve functional performance more than GM-CSF alone or supervised treadmill exercise alone. Mary McDermott, MD, of Northwestern University, Chicago, will present the primary endpoint of change in 6-minute walk performance at 12-weeks’ follow-up, as well as several secondary outcomes.
- ALLSTAR: Timothy Henry, MD, of the Cedars-Sinai Heart Institute, Los Angeles, will present the phase 1-2 ALLSTAR (Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration) study, which compared allogeneic cardiosphere-derived cells (CAP-1002) to placebo in order to find whether it is safe and effective in decreasing infarct size in patients with an MI.
- HOPE-Duchenne: This phase 1-2 study randomized men with cardiomyopathy secondary to Duchenne muscular dystrophy to receive CAP-1002 cells or usual care; its primary outcome is safety. Ronald Victor, MD, will present the results.
chackett@frontlinemedcom.com
On Twitter @cardionews
The final Late-Breaking Science session delves into innovative therapies and novel applications, including two phase 1-2 stem cell trials, an early trial in toxin treatments to prevent atrial fibrillation, a phase 1 test of an interatrial shunt device for heart failure with preserved ejection fraction, and more:
- TNT-POAF: Nathan Waldron, MD, of Duke University, Durham, N.C., will present results of a trial aiming to prevent postoperative atrial fibrillation with the use of temporary toxin treatment.
- REDUCE LAP–HF 1: In what the investigators call the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF, an inter-atrial shunt device designed to provide continuous and dynamic decompression of the left atrium. Sanjiv J Shah, MD, of Northwestern University will present the study, which holds the hypothesis that the device may reduce symptoms and slow the progression of heart failure.
- PROPEL: This study tested the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with supervised treadmill exercise in patients with peripheral artery disease would significantly improve functional performance more than GM-CSF alone or supervised treadmill exercise alone. Mary McDermott, MD, of Northwestern University, Chicago, will present the primary endpoint of change in 6-minute walk performance at 12-weeks’ follow-up, as well as several secondary outcomes.
- ALLSTAR: Timothy Henry, MD, of the Cedars-Sinai Heart Institute, Los Angeles, will present the phase 1-2 ALLSTAR (Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration) study, which compared allogeneic cardiosphere-derived cells (CAP-1002) to placebo in order to find whether it is safe and effective in decreasing infarct size in patients with an MI.
- HOPE-Duchenne: This phase 1-2 study randomized men with cardiomyopathy secondary to Duchenne muscular dystrophy to receive CAP-1002 cells or usual care; its primary outcome is safety. Ronald Victor, MD, will present the results.
chackett@frontlinemedcom.com
On Twitter @cardionews
The final Late-Breaking Science session delves into innovative therapies and novel applications, including two phase 1-2 stem cell trials, an early trial in toxin treatments to prevent atrial fibrillation, a phase 1 test of an interatrial shunt device for heart failure with preserved ejection fraction, and more:
- TNT-POAF: Nathan Waldron, MD, of Duke University, Durham, N.C., will present results of a trial aiming to prevent postoperative atrial fibrillation with the use of temporary toxin treatment.
- REDUCE LAP–HF 1: In what the investigators call the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF, an inter-atrial shunt device designed to provide continuous and dynamic decompression of the left atrium. Sanjiv J Shah, MD, of Northwestern University will present the study, which holds the hypothesis that the device may reduce symptoms and slow the progression of heart failure.
- PROPEL: This study tested the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with supervised treadmill exercise in patients with peripheral artery disease would significantly improve functional performance more than GM-CSF alone or supervised treadmill exercise alone. Mary McDermott, MD, of Northwestern University, Chicago, will present the primary endpoint of change in 6-minute walk performance at 12-weeks’ follow-up, as well as several secondary outcomes.
- ALLSTAR: Timothy Henry, MD, of the Cedars-Sinai Heart Institute, Los Angeles, will present the phase 1-2 ALLSTAR (Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration) study, which compared allogeneic cardiosphere-derived cells (CAP-1002) to placebo in order to find whether it is safe and effective in decreasing infarct size in patients with an MI.
- HOPE-Duchenne: This phase 1-2 study randomized men with cardiomyopathy secondary to Duchenne muscular dystrophy to receive CAP-1002 cells or usual care; its primary outcome is safety. Ronald Victor, MD, will present the results.
chackett@frontlinemedcom.com
On Twitter @cardionews
CV outcomes better with SGLT2 inhibitor than DPP4 inhibitor in T2DM study
LISBON – The sodium-glucose co-transporter 2 (SGLT-2) inhibitor dapagliflozin (Farxiga) posed a lower risk of cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidase-4 inhibitors in a large real-world, observational study.
In CVD-REAL NORDIC, treatment with the SGLT-2 inhibitor reduced the incidence of major cardiovascular adverse events by 21% as compared to DDP-4 inhibitors (hazard ratio, 0.79; 95% confidence interval, 0.67-0.94; P = .006).
Anna Norhammar, MD, PhD, of the Institute of Medicine, Cardiology Unit, at Karolinska Institutet in Stockholm, presented the findings at the annual meeting of the European Association for the Study of Diabetes.
She said: “These results are in line with previous clinical trials and meta-analyses, but extend the results to a broader CV risk population and with a commonly used comparator.”
Indeed, the findings build on those from the widely reported EMPA-REG Outcome (New Engl J Med. 2015;373;2117-8) and CANVAS (New Engl J Med. 2017;377:644-7) randomized controlled trials. These trials respectively showed empagliflozin and canagliflozin significantly reduced the risk for MACE and heart failure in patients with T2DM versus placebo. As the majority of patients in these trials had established CV disease, this suggested a class effect for SGLT2 inhibitors, Dr. Norhammar explained.
CVD-REAL NORDIC is part of a larger, multinational, observational, comparative effectiveness study looking at the real-world effect of SGLT2 inhibitors versus other glucose-lowering drugs on CV outcomes in patients with T2DM. Altogether around 90,000 patients have been recruited in Sweden, Norway, and Denmark.
Previously, Dr. Norhammar and co-investigators have reported that SGLT2 inhibitors lowered MACE (HR, 0.78; 95% CI 0.69–0.87, P less than .0001) and heart failure hospitalization (HR, 0.70; 95% CI 0.61–0.81, P less than .0001) relative to all glucose-lowering drugs (Lancet Diabetes Endocrinol. 2017;709–17).
“However, the comparator group used in that study, other [glucose-lowering drugs], consisted of almost 50% patients with T2DM treated with insulin or sul[f]onylureas,” they wrote in Diabetes, Obesity and Metabolism (8 Sep., doi: 10.1111/dom.13077). Insulin or sulfonylureas, they add, “have been shown to have increased associated CV risks” compared with DPP4 inhibitors and it is “not fully clear to what extent this could have influenced risk estimates.”
Furthermore, the CVD-NORDIC investigators note that the comparator group reflected real-world practice and it is important to look at treatment strategies more specifically, hence why they decided to do an analysis comparing SGLT2 and DPP4 inhibitors.
The study population for the current analysis consisted of 40,909 patients with T2DM who were newly initiated on either dapagliflozin (n=10,227) or a DPP4 inhibitor (n=30,682) between 2012 and 2015. The mean age was 61 years, and around 23% had prior CV disease and 5% had previous heart failure.
After a mean follow-up of 11.3 months, 177 MACE events had occurred among the 10,227 dapagliflozin-treated patients and 695 among the 30,681 DPP4 inhibitor-treated patients, giving respective event rates of 1.86 and 2.34 per 100 patient years. MACE was defined as a composite of nonfatal myocardial infarction, nonfatal stroke, and CV mortality.
“Dapagliflozin is the most commonly used SGLT2 inhibitor in the Nordic countries,” Dr. Norhammar said, explaining why this particular SGLT2 inhibitor was used in the analysis.
While there was a clear benefit of using dapagliflozin over DPP4 inhibitors in terms of MACE, heart failure hospitalization, and all-cause mortality, there was a “neutral” effect on atrial fibrillation and severe hypoglycaemia, with respective HRs of 0.92 (95% CI 0.76–1.12; P = .41) and 0.94 (95% CI 0.74–1.19; P = .62).
Dr. Norhammar said these “neutral results for atrial fibrillation and severe hypoglycaemia,” were “in line with expectations, and suggest a low likelihood of confounding.”
As this was an observational study, one of the limitations is that could be confounding factors that could not be adequately matched in the analysis. The events were not adjudicated and the study didn’t look at safety.
Dr. Norhammar noted that the results of the DECLARE-TIMI 58 trials were now needed to see if the potential CV benefits of using an SGLT2 inhibitor over other gluc0se-lowering medications might extend into patients at lower CV risk.
AstraZeneca supported the study.
Dr. Norhammar disclosed acting as a consultant to and receiving honoraria from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Novo Nordisk, and MSD Sweden.
LISBON – The sodium-glucose co-transporter 2 (SGLT-2) inhibitor dapagliflozin (Farxiga) posed a lower risk of cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidase-4 inhibitors in a large real-world, observational study.
In CVD-REAL NORDIC, treatment with the SGLT-2 inhibitor reduced the incidence of major cardiovascular adverse events by 21% as compared to DDP-4 inhibitors (hazard ratio, 0.79; 95% confidence interval, 0.67-0.94; P = .006).
Anna Norhammar, MD, PhD, of the Institute of Medicine, Cardiology Unit, at Karolinska Institutet in Stockholm, presented the findings at the annual meeting of the European Association for the Study of Diabetes.
She said: “These results are in line with previous clinical trials and meta-analyses, but extend the results to a broader CV risk population and with a commonly used comparator.”
Indeed, the findings build on those from the widely reported EMPA-REG Outcome (New Engl J Med. 2015;373;2117-8) and CANVAS (New Engl J Med. 2017;377:644-7) randomized controlled trials. These trials respectively showed empagliflozin and canagliflozin significantly reduced the risk for MACE and heart failure in patients with T2DM versus placebo. As the majority of patients in these trials had established CV disease, this suggested a class effect for SGLT2 inhibitors, Dr. Norhammar explained.
CVD-REAL NORDIC is part of a larger, multinational, observational, comparative effectiveness study looking at the real-world effect of SGLT2 inhibitors versus other glucose-lowering drugs on CV outcomes in patients with T2DM. Altogether around 90,000 patients have been recruited in Sweden, Norway, and Denmark.
Previously, Dr. Norhammar and co-investigators have reported that SGLT2 inhibitors lowered MACE (HR, 0.78; 95% CI 0.69–0.87, P less than .0001) and heart failure hospitalization (HR, 0.70; 95% CI 0.61–0.81, P less than .0001) relative to all glucose-lowering drugs (Lancet Diabetes Endocrinol. 2017;709–17).
“However, the comparator group used in that study, other [glucose-lowering drugs], consisted of almost 50% patients with T2DM treated with insulin or sul[f]onylureas,” they wrote in Diabetes, Obesity and Metabolism (8 Sep., doi: 10.1111/dom.13077). Insulin or sulfonylureas, they add, “have been shown to have increased associated CV risks” compared with DPP4 inhibitors and it is “not fully clear to what extent this could have influenced risk estimates.”
Furthermore, the CVD-NORDIC investigators note that the comparator group reflected real-world practice and it is important to look at treatment strategies more specifically, hence why they decided to do an analysis comparing SGLT2 and DPP4 inhibitors.
The study population for the current analysis consisted of 40,909 patients with T2DM who were newly initiated on either dapagliflozin (n=10,227) or a DPP4 inhibitor (n=30,682) between 2012 and 2015. The mean age was 61 years, and around 23% had prior CV disease and 5% had previous heart failure.
After a mean follow-up of 11.3 months, 177 MACE events had occurred among the 10,227 dapagliflozin-treated patients and 695 among the 30,681 DPP4 inhibitor-treated patients, giving respective event rates of 1.86 and 2.34 per 100 patient years. MACE was defined as a composite of nonfatal myocardial infarction, nonfatal stroke, and CV mortality.
“Dapagliflozin is the most commonly used SGLT2 inhibitor in the Nordic countries,” Dr. Norhammar said, explaining why this particular SGLT2 inhibitor was used in the analysis.
While there was a clear benefit of using dapagliflozin over DPP4 inhibitors in terms of MACE, heart failure hospitalization, and all-cause mortality, there was a “neutral” effect on atrial fibrillation and severe hypoglycaemia, with respective HRs of 0.92 (95% CI 0.76–1.12; P = .41) and 0.94 (95% CI 0.74–1.19; P = .62).
Dr. Norhammar said these “neutral results for atrial fibrillation and severe hypoglycaemia,” were “in line with expectations, and suggest a low likelihood of confounding.”
As this was an observational study, one of the limitations is that could be confounding factors that could not be adequately matched in the analysis. The events were not adjudicated and the study didn’t look at safety.
Dr. Norhammar noted that the results of the DECLARE-TIMI 58 trials were now needed to see if the potential CV benefits of using an SGLT2 inhibitor over other gluc0se-lowering medications might extend into patients at lower CV risk.
AstraZeneca supported the study.
Dr. Norhammar disclosed acting as a consultant to and receiving honoraria from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Novo Nordisk, and MSD Sweden.
LISBON – The sodium-glucose co-transporter 2 (SGLT-2) inhibitor dapagliflozin (Farxiga) posed a lower risk of cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidase-4 inhibitors in a large real-world, observational study.
In CVD-REAL NORDIC, treatment with the SGLT-2 inhibitor reduced the incidence of major cardiovascular adverse events by 21% as compared to DDP-4 inhibitors (hazard ratio, 0.79; 95% confidence interval, 0.67-0.94; P = .006).
Anna Norhammar, MD, PhD, of the Institute of Medicine, Cardiology Unit, at Karolinska Institutet in Stockholm, presented the findings at the annual meeting of the European Association for the Study of Diabetes.
She said: “These results are in line with previous clinical trials and meta-analyses, but extend the results to a broader CV risk population and with a commonly used comparator.”
Indeed, the findings build on those from the widely reported EMPA-REG Outcome (New Engl J Med. 2015;373;2117-8) and CANVAS (New Engl J Med. 2017;377:644-7) randomized controlled trials. These trials respectively showed empagliflozin and canagliflozin significantly reduced the risk for MACE and heart failure in patients with T2DM versus placebo. As the majority of patients in these trials had established CV disease, this suggested a class effect for SGLT2 inhibitors, Dr. Norhammar explained.
CVD-REAL NORDIC is part of a larger, multinational, observational, comparative effectiveness study looking at the real-world effect of SGLT2 inhibitors versus other glucose-lowering drugs on CV outcomes in patients with T2DM. Altogether around 90,000 patients have been recruited in Sweden, Norway, and Denmark.
Previously, Dr. Norhammar and co-investigators have reported that SGLT2 inhibitors lowered MACE (HR, 0.78; 95% CI 0.69–0.87, P less than .0001) and heart failure hospitalization (HR, 0.70; 95% CI 0.61–0.81, P less than .0001) relative to all glucose-lowering drugs (Lancet Diabetes Endocrinol. 2017;709–17).
“However, the comparator group used in that study, other [glucose-lowering drugs], consisted of almost 50% patients with T2DM treated with insulin or sul[f]onylureas,” they wrote in Diabetes, Obesity and Metabolism (8 Sep., doi: 10.1111/dom.13077). Insulin or sulfonylureas, they add, “have been shown to have increased associated CV risks” compared with DPP4 inhibitors and it is “not fully clear to what extent this could have influenced risk estimates.”
Furthermore, the CVD-NORDIC investigators note that the comparator group reflected real-world practice and it is important to look at treatment strategies more specifically, hence why they decided to do an analysis comparing SGLT2 and DPP4 inhibitors.
The study population for the current analysis consisted of 40,909 patients with T2DM who were newly initiated on either dapagliflozin (n=10,227) or a DPP4 inhibitor (n=30,682) between 2012 and 2015. The mean age was 61 years, and around 23% had prior CV disease and 5% had previous heart failure.
After a mean follow-up of 11.3 months, 177 MACE events had occurred among the 10,227 dapagliflozin-treated patients and 695 among the 30,681 DPP4 inhibitor-treated patients, giving respective event rates of 1.86 and 2.34 per 100 patient years. MACE was defined as a composite of nonfatal myocardial infarction, nonfatal stroke, and CV mortality.
“Dapagliflozin is the most commonly used SGLT2 inhibitor in the Nordic countries,” Dr. Norhammar said, explaining why this particular SGLT2 inhibitor was used in the analysis.
While there was a clear benefit of using dapagliflozin over DPP4 inhibitors in terms of MACE, heart failure hospitalization, and all-cause mortality, there was a “neutral” effect on atrial fibrillation and severe hypoglycaemia, with respective HRs of 0.92 (95% CI 0.76–1.12; P = .41) and 0.94 (95% CI 0.74–1.19; P = .62).
Dr. Norhammar said these “neutral results for atrial fibrillation and severe hypoglycaemia,” were “in line with expectations, and suggest a low likelihood of confounding.”
As this was an observational study, one of the limitations is that could be confounding factors that could not be adequately matched in the analysis. The events were not adjudicated and the study didn’t look at safety.
Dr. Norhammar noted that the results of the DECLARE-TIMI 58 trials were now needed to see if the potential CV benefits of using an SGLT2 inhibitor over other gluc0se-lowering medications might extend into patients at lower CV risk.
AstraZeneca supported the study.
Dr. Norhammar disclosed acting as a consultant to and receiving honoraria from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Novo Nordisk, and MSD Sweden.
AT EASD 2017
Key clinical point:
Major finding: Hazard ratios for MACE, heart failure hospitalization, and all-cause mortality were a respective 0.79, 0.62, and 0.59, comparing SGLT2 with DPP4 inhibitors.
Data source: CVD-NORDIC, part of a multinational, observational study comparing the real-world effect of SGLT2 inhibitors versus other glucose-lowering drugs on CV outcomes in patients with T2DM.
Disclosures: AstraZeneca supported the study. The presenting author disclosed acting as a consultant to and receiving honoraria from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Novo Nordisk, and MSD Sweden.
Why VADS is gaining ground in pediatrics
The miniaturization of continuous-flow ventricular assist devices has launched the era of continuous-flow VAD support in pediatric patients, and the trend may accelerate with the introduction of a continuous-flow device designed specifically for small children. In an expert opinion in the Journal of Thoracic and Cardiovascular Surgery, Iki Adachi, MD, of Baylor College of Medicine in Houston, said the emerging science of continuous-flow VADs in children promises to solve problems like device size mismatch, hospital-only VADs, and chronic therapy (J Thorac Cardiovasc Surg. 2017 Oct;154:1358-61). “With ongoing device miniaturization, enthusiasm has been growing among pediatric physicians for the use of continuous-flow VADs in children,” Dr. Adachi said. He noted the introduction of a continuous-flow device for small children, the Infant Jarvik 2015, “may further accelerate the trend.”
Dr. Adachi cited PediMACS reports that stated that more than half of the long-term devices now registered are continuous-flow devices, and that continuous-flow VADs comprised 62% of all durable VAD implants in the third quarter of 2016. “With the encouraging results recorded to date, the use of continuous-flow devices in the pediatric population is rapidly increasing,” he said.
Miniaturization has addressed the problem of size mismatch when using continuous-flow VAD devices in children, he said, noting that use of the Infant Jarvik device may be expanded even further to children as small at 8 kg or less. The PumpKIN trial(Pumps for Kids, Infants, and Neonates), which is evaluating the Infant Jarvik 2015 vs. the Berlin Heart EXCOR, could provide answers on the feasibility of continuous-flow VADs in small children.
“Based on experience with the chronic animal model, I believe that the Infant Jarvik device will properly fit the patients included in the trial,” he said.
Continuous-flow VAD in children also holds potential for managing these patients outside the hospital setting. “Outpatient management of children with continuous-flow VADs has been shown to be feasible,” he said, adding that the PediMACS registry has reported that only 45% of patients have been managed this way. “Nonetheless, with maturation of the pediatric field, outpatient management will become routine rather than the exception,” he said.
Greater use of continuous-flow VADs also may create opportunities to improve the status and suitability for transplantation of children with severe heart failure, he said. He gave as an example his group’s practice at Houston’s Texas Children’s Hospital, which is to deactivate patients on the transplant wait list for 3 months once they start continuous-flow VAD support. “A postoperative ‘grace period’ affords protected opportunities for both physical and psychological recovery,” he said. This timeout of sorts also affords the care team time to assess the myocardium for possible functional recovery.
In patients who are not good candidates for transplantation, durable continuous-flow VADs may provide chronic therapy, and in time, these patients may become suitable transplant candidates, said Dr. Adachi. “Bypassing such an unfavorable period for transplantation with prolonged VAD support may be a reasonable approach,” he said.
Patients with failing single-ventricle circulation also may benefit from VAD support, although the challenges facing this population are more profound than in other groups, Dr. Adachi said. VAD support for single-ventricle disease is sparse, but these patients require careful evaluation of the nature of their condition. “If systolic dysfunction is the predominant cause of circulatory failure, then VAD support for the failing systemic ventricle will likely improve hemodynamics,” said Dr. Adachi. VAD support also could help the patient move through the various stages of palliation.
“Again, the emphasis is not just on simply keeping the patient alive until a donor organ becomes available; rather, attention is refocused on overall health beyond survival, which may eventually affect transplantation candidacy and even post transplantation outcome,” Dr. Adachi concluded.
Dr. Adachi serves as a consultant and proctor for Berlin Heart and HeartWare, and as a consultant for the New England Research Institute related to the PumpKIN trial.
The miniaturization of continuous-flow ventricular assist devices has launched the era of continuous-flow VAD support in pediatric patients, and the trend may accelerate with the introduction of a continuous-flow device designed specifically for small children. In an expert opinion in the Journal of Thoracic and Cardiovascular Surgery, Iki Adachi, MD, of Baylor College of Medicine in Houston, said the emerging science of continuous-flow VADs in children promises to solve problems like device size mismatch, hospital-only VADs, and chronic therapy (J Thorac Cardiovasc Surg. 2017 Oct;154:1358-61). “With ongoing device miniaturization, enthusiasm has been growing among pediatric physicians for the use of continuous-flow VADs in children,” Dr. Adachi said. He noted the introduction of a continuous-flow device for small children, the Infant Jarvik 2015, “may further accelerate the trend.”
Dr. Adachi cited PediMACS reports that stated that more than half of the long-term devices now registered are continuous-flow devices, and that continuous-flow VADs comprised 62% of all durable VAD implants in the third quarter of 2016. “With the encouraging results recorded to date, the use of continuous-flow devices in the pediatric population is rapidly increasing,” he said.
Miniaturization has addressed the problem of size mismatch when using continuous-flow VAD devices in children, he said, noting that use of the Infant Jarvik device may be expanded even further to children as small at 8 kg or less. The PumpKIN trial(Pumps for Kids, Infants, and Neonates), which is evaluating the Infant Jarvik 2015 vs. the Berlin Heart EXCOR, could provide answers on the feasibility of continuous-flow VADs in small children.
“Based on experience with the chronic animal model, I believe that the Infant Jarvik device will properly fit the patients included in the trial,” he said.
Continuous-flow VAD in children also holds potential for managing these patients outside the hospital setting. “Outpatient management of children with continuous-flow VADs has been shown to be feasible,” he said, adding that the PediMACS registry has reported that only 45% of patients have been managed this way. “Nonetheless, with maturation of the pediatric field, outpatient management will become routine rather than the exception,” he said.
Greater use of continuous-flow VADs also may create opportunities to improve the status and suitability for transplantation of children with severe heart failure, he said. He gave as an example his group’s practice at Houston’s Texas Children’s Hospital, which is to deactivate patients on the transplant wait list for 3 months once they start continuous-flow VAD support. “A postoperative ‘grace period’ affords protected opportunities for both physical and psychological recovery,” he said. This timeout of sorts also affords the care team time to assess the myocardium for possible functional recovery.
In patients who are not good candidates for transplantation, durable continuous-flow VADs may provide chronic therapy, and in time, these patients may become suitable transplant candidates, said Dr. Adachi. “Bypassing such an unfavorable period for transplantation with prolonged VAD support may be a reasonable approach,” he said.
Patients with failing single-ventricle circulation also may benefit from VAD support, although the challenges facing this population are more profound than in other groups, Dr. Adachi said. VAD support for single-ventricle disease is sparse, but these patients require careful evaluation of the nature of their condition. “If systolic dysfunction is the predominant cause of circulatory failure, then VAD support for the failing systemic ventricle will likely improve hemodynamics,” said Dr. Adachi. VAD support also could help the patient move through the various stages of palliation.
“Again, the emphasis is not just on simply keeping the patient alive until a donor organ becomes available; rather, attention is refocused on overall health beyond survival, which may eventually affect transplantation candidacy and even post transplantation outcome,” Dr. Adachi concluded.
Dr. Adachi serves as a consultant and proctor for Berlin Heart and HeartWare, and as a consultant for the New England Research Institute related to the PumpKIN trial.
The miniaturization of continuous-flow ventricular assist devices has launched the era of continuous-flow VAD support in pediatric patients, and the trend may accelerate with the introduction of a continuous-flow device designed specifically for small children. In an expert opinion in the Journal of Thoracic and Cardiovascular Surgery, Iki Adachi, MD, of Baylor College of Medicine in Houston, said the emerging science of continuous-flow VADs in children promises to solve problems like device size mismatch, hospital-only VADs, and chronic therapy (J Thorac Cardiovasc Surg. 2017 Oct;154:1358-61). “With ongoing device miniaturization, enthusiasm has been growing among pediatric physicians for the use of continuous-flow VADs in children,” Dr. Adachi said. He noted the introduction of a continuous-flow device for small children, the Infant Jarvik 2015, “may further accelerate the trend.”
Dr. Adachi cited PediMACS reports that stated that more than half of the long-term devices now registered are continuous-flow devices, and that continuous-flow VADs comprised 62% of all durable VAD implants in the third quarter of 2016. “With the encouraging results recorded to date, the use of continuous-flow devices in the pediatric population is rapidly increasing,” he said.
Miniaturization has addressed the problem of size mismatch when using continuous-flow VAD devices in children, he said, noting that use of the Infant Jarvik device may be expanded even further to children as small at 8 kg or less. The PumpKIN trial(Pumps for Kids, Infants, and Neonates), which is evaluating the Infant Jarvik 2015 vs. the Berlin Heart EXCOR, could provide answers on the feasibility of continuous-flow VADs in small children.
“Based on experience with the chronic animal model, I believe that the Infant Jarvik device will properly fit the patients included in the trial,” he said.
Continuous-flow VAD in children also holds potential for managing these patients outside the hospital setting. “Outpatient management of children with continuous-flow VADs has been shown to be feasible,” he said, adding that the PediMACS registry has reported that only 45% of patients have been managed this way. “Nonetheless, with maturation of the pediatric field, outpatient management will become routine rather than the exception,” he said.
Greater use of continuous-flow VADs also may create opportunities to improve the status and suitability for transplantation of children with severe heart failure, he said. He gave as an example his group’s practice at Houston’s Texas Children’s Hospital, which is to deactivate patients on the transplant wait list for 3 months once they start continuous-flow VAD support. “A postoperative ‘grace period’ affords protected opportunities for both physical and psychological recovery,” he said. This timeout of sorts also affords the care team time to assess the myocardium for possible functional recovery.
In patients who are not good candidates for transplantation, durable continuous-flow VADs may provide chronic therapy, and in time, these patients may become suitable transplant candidates, said Dr. Adachi. “Bypassing such an unfavorable period for transplantation with prolonged VAD support may be a reasonable approach,” he said.
Patients with failing single-ventricle circulation also may benefit from VAD support, although the challenges facing this population are more profound than in other groups, Dr. Adachi said. VAD support for single-ventricle disease is sparse, but these patients require careful evaluation of the nature of their condition. “If systolic dysfunction is the predominant cause of circulatory failure, then VAD support for the failing systemic ventricle will likely improve hemodynamics,” said Dr. Adachi. VAD support also could help the patient move through the various stages of palliation.
“Again, the emphasis is not just on simply keeping the patient alive until a donor organ becomes available; rather, attention is refocused on overall health beyond survival, which may eventually affect transplantation candidacy and even post transplantation outcome,” Dr. Adachi concluded.
Dr. Adachi serves as a consultant and proctor for Berlin Heart and HeartWare, and as a consultant for the New England Research Institute related to the PumpKIN trial.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Advances in continuous-flow ventricular assist devices (VADs) promise a paradigm shift in pediatrics.
Major finding: Device miniaturization is solving problems such as size mismatch, inpatients on VADs, and chronic therapy.
Data source: Expert opinion drawing on PediMACS reports and published trials of continuous-flow VAD.
Disclosures: Dr. Adachi serves as a consultant and proctor for Berlin Heart and HeartWare and as a consultant for the New England Research Institute related to the PumpKIN trial.
Cardiogenic shock boosts PAH readmissions 10-fold
TORONTO – Cardiogenic shock, acute kidney injury, and chronic obstructive pulmonary disease were the top drivers of 30-day rehospitalizations in U.S. patients after an index hospitalization for pulmonary artery hypertension, based on an analysis of U.S. national data from 2013.
An episode of cardiogenic shock boosted 30-day rehospitalizations nearly 10-fold in recently discharged pulmonary artery hypertension (PAH) patients. A history of chronic obstructive pulmonary disease (COPD) linked with a threefold higher rehospitalization rate, and acute kidney injury linked with a doubled number of 30-day rehospitalizations, Kshitij Chatterjee, MD, said at the CHEST annual meeting.
The powerful impact of cardiogenic shock in particular suggests that interventions that improve patient compliance with stabilizing treatments following an index PAH hospitalization might be effective at preventing a patient’s quick return to the hospital. Contacting PAH patients a week after their index hospitalization discharge to make sure they are compliant with their diuretic regimen, for example, might help prevent a decompensation that then leads to cardiogenic shock and a return trip to the hospital, Dr. Chatterjee suggested.
Follow-up of PAH patients after an index hospitalization “is probably the single most important thing, because it can help with compliance,” he said in an interview.
The rehospitalizations he studied could be for any cause. His analysis showed that the most common cause of rehospitalization was heart failure, which caused 23% of the rehospitalizations, followed by pulmonary hypertension that caused 20%, and acute kidney injury, responsible for 11% of the 30-day rehospitalizations.
Dr. Chatterjee’s study used data collected during 2013 in the National Readmissions Database, run by the federal Agency for Healthcare Quality and Research. During that period, 776 patients entered a U.S. hospital with a primary diagnosis of PAH. During the 30 days following discharge, 114 (15%) returned to the hospital. During the second hospitalization 8% died, and the median length of stay for those who remained alive was 7 days.
Dr. Chatterjee highlighted that the modest number of index hospitalizations for PAH, as well as 30-day rehospitalizations he found in 2013, make it highly unlikely that PAH rehospitalizations will become a target for Medicare penalties as has been done for heart failure, pneumonia, COPD, and a few other disorders. But he stressed that patients with PAH who need rehospitalization generally have a highly compromised quality of life that potentially could be avoided by better management, which could prevent the need for rehospitalization.
Dr. Chatterjee had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
TORONTO – Cardiogenic shock, acute kidney injury, and chronic obstructive pulmonary disease were the top drivers of 30-day rehospitalizations in U.S. patients after an index hospitalization for pulmonary artery hypertension, based on an analysis of U.S. national data from 2013.
An episode of cardiogenic shock boosted 30-day rehospitalizations nearly 10-fold in recently discharged pulmonary artery hypertension (PAH) patients. A history of chronic obstructive pulmonary disease (COPD) linked with a threefold higher rehospitalization rate, and acute kidney injury linked with a doubled number of 30-day rehospitalizations, Kshitij Chatterjee, MD, said at the CHEST annual meeting.
The powerful impact of cardiogenic shock in particular suggests that interventions that improve patient compliance with stabilizing treatments following an index PAH hospitalization might be effective at preventing a patient’s quick return to the hospital. Contacting PAH patients a week after their index hospitalization discharge to make sure they are compliant with their diuretic regimen, for example, might help prevent a decompensation that then leads to cardiogenic shock and a return trip to the hospital, Dr. Chatterjee suggested.
Follow-up of PAH patients after an index hospitalization “is probably the single most important thing, because it can help with compliance,” he said in an interview.
The rehospitalizations he studied could be for any cause. His analysis showed that the most common cause of rehospitalization was heart failure, which caused 23% of the rehospitalizations, followed by pulmonary hypertension that caused 20%, and acute kidney injury, responsible for 11% of the 30-day rehospitalizations.
Dr. Chatterjee’s study used data collected during 2013 in the National Readmissions Database, run by the federal Agency for Healthcare Quality and Research. During that period, 776 patients entered a U.S. hospital with a primary diagnosis of PAH. During the 30 days following discharge, 114 (15%) returned to the hospital. During the second hospitalization 8% died, and the median length of stay for those who remained alive was 7 days.
Dr. Chatterjee highlighted that the modest number of index hospitalizations for PAH, as well as 30-day rehospitalizations he found in 2013, make it highly unlikely that PAH rehospitalizations will become a target for Medicare penalties as has been done for heart failure, pneumonia, COPD, and a few other disorders. But he stressed that patients with PAH who need rehospitalization generally have a highly compromised quality of life that potentially could be avoided by better management, which could prevent the need for rehospitalization.
Dr. Chatterjee had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
TORONTO – Cardiogenic shock, acute kidney injury, and chronic obstructive pulmonary disease were the top drivers of 30-day rehospitalizations in U.S. patients after an index hospitalization for pulmonary artery hypertension, based on an analysis of U.S. national data from 2013.
An episode of cardiogenic shock boosted 30-day rehospitalizations nearly 10-fold in recently discharged pulmonary artery hypertension (PAH) patients. A history of chronic obstructive pulmonary disease (COPD) linked with a threefold higher rehospitalization rate, and acute kidney injury linked with a doubled number of 30-day rehospitalizations, Kshitij Chatterjee, MD, said at the CHEST annual meeting.
The powerful impact of cardiogenic shock in particular suggests that interventions that improve patient compliance with stabilizing treatments following an index PAH hospitalization might be effective at preventing a patient’s quick return to the hospital. Contacting PAH patients a week after their index hospitalization discharge to make sure they are compliant with their diuretic regimen, for example, might help prevent a decompensation that then leads to cardiogenic shock and a return trip to the hospital, Dr. Chatterjee suggested.
Follow-up of PAH patients after an index hospitalization “is probably the single most important thing, because it can help with compliance,” he said in an interview.
The rehospitalizations he studied could be for any cause. His analysis showed that the most common cause of rehospitalization was heart failure, which caused 23% of the rehospitalizations, followed by pulmonary hypertension that caused 20%, and acute kidney injury, responsible for 11% of the 30-day rehospitalizations.
Dr. Chatterjee’s study used data collected during 2013 in the National Readmissions Database, run by the federal Agency for Healthcare Quality and Research. During that period, 776 patients entered a U.S. hospital with a primary diagnosis of PAH. During the 30 days following discharge, 114 (15%) returned to the hospital. During the second hospitalization 8% died, and the median length of stay for those who remained alive was 7 days.
Dr. Chatterjee highlighted that the modest number of index hospitalizations for PAH, as well as 30-day rehospitalizations he found in 2013, make it highly unlikely that PAH rehospitalizations will become a target for Medicare penalties as has been done for heart failure, pneumonia, COPD, and a few other disorders. But he stressed that patients with PAH who need rehospitalization generally have a highly compromised quality of life that potentially could be avoided by better management, which could prevent the need for rehospitalization.
Dr. Chatterjee had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT CHEST 2017
Key clinical point:
Major finding: Patients with cardiogenic shock following PAH hospitalization had a 9.7-fold increased rate of 30-day rehospitalization, compared with patients without shock.
Data source: The National Readmissions Database, which included 776 index U.S. hospitalizations for pulmonary arterial hospitalization during 2013.
Disclosures: Dr. Chatterjee had no disclosures.
Generic, brand-name levothyroxine have similar cardiovascular outcomes
VICTORIA, B.C. – Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.
Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.
However, monthly total medication costs with the brand-name medication were more than twice those with the generic.
“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”
He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.
“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”
Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.
For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.
The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.
Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.
The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).
Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).
Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.
When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).
“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”
The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”
At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.
Dr. Smallridge reported that he had no relevant conflicts of interest.
VICTORIA, B.C. – Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.
Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.
However, monthly total medication costs with the brand-name medication were more than twice those with the generic.
“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”
He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.
“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”
Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.
For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.
The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.
Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.
The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).
Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).
Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.
When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).
“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”
The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”
At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.
Dr. Smallridge reported that he had no relevant conflicts of interest.
VICTORIA, B.C. – Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.
Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.
However, monthly total medication costs with the brand-name medication were more than twice those with the generic.
“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”
He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.
“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”
Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.
For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.
The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.
Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.
The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).
Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).
Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.
When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).
“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”
The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”
At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.
Dr. Smallridge reported that he had no relevant conflicts of interest.
AT ATA 2017
Key clinical point:
Major finding: Patients taking brand-name versus generic levothyroxine had similar risks of hospitalization for atrial fibrillation (HR, 1.22; P = .19), myocardial infarction (0.86; P = .35), congestive heart failure (0.88; P = .41), and stroke (0.77; P = .05).
Data source: A retrospective cohort study of 87,902 propensity-matched hypothyroid patients starting generic or brand-name levothyroxine.
Disclosures: Dr. Smallridge reported that he had no relevant conflicts of interest.
New appropriate use criteria reframe severe aortic stenosis
New appropriate use criteria (AUC) for severe aortic stenosis (AS) run the full gamut of clinical scenarios and treatment options.
“Cardiology is seeing a radical change in the management of aortic stenosis. This new document incorporates all therapies currently available in the world,” said Vinod H. Thourani, MD, who served on the AUC’s writing group on behalf of the American College of Cardiology. “The AUC highlights state-of-the-art therapy for aortic stenosis and, even more importantly, helps clarify the right indications for surgical and transcatheter valve replacement.”
Surgical risk is assessed based on the Society of Thoracic Surgeons Predicted Risk of Mortality score plus additional anatomic and functional considerations that should be assessed by a multidisciplinary heart team. The AUC repeatedly emphasizes this team’s importance. “Multiple comorbidities can change the pathway of treating AS, and this determination is best made by a heart team that at least includes a noninvasive cardiologist, an interventional cardiologist, and a cardiac surgeon,” Dr. Thourani said. “That’s how patients get the best care.”
Historically, aortic stenosis typically was managed medically or with balloon aortic valvuloplasty (BAV) or open aortic valve replacement, Dr. Thourani said. However, BAV is less common now, and indications for surgical or transcatheter aortic valve replacement (SAVR or TAVR) are expanding. Balloon aortic valvuloplasty sometimes does provide palliative treatment or serve as a bridge to a decision, the AUC states. For example, for a high-risk patient with severe aortic stenosis and severe secondary mitral regurgitation, BAV can help the heart team decide whether TAVR alone will improve mitral regurgitation or whether a double valve procedure is preferable.
Regardless of risk score, the AUC considers a wait-and-see approach as potentially appropriate for patients with asymptomatic high-grade AS whose left ventricular ejection fraction is at least 50%, peak aortic valve velocity is 4.0-4.9 m/sec, and exercise stress test is normal and with no predictors of symptom onset or rapid progression. Asymptomatic patients who are likely to become symptomatic but who have a low risk of sudden death are candidates for intervention (rated “appropriate”) or medical management (“may be appropriate”). In contrast, a positive stress test in an otherwise asymptomatic patient merits consideration of SAVR or TAVR regardless of surgical risk. The recommendations for asymptomatic patients reflect a lack of head-to-head trials in this population, Dr. Thourani said. “We don’t have good randomized data to show one therapy is better than another.”
Symptomatic, high-gradient, severe AS with associated coronary artery disease merits consideration of SAVR with coronary artery bypass graft or, in some cases, TAVR with percutaneous coronary intervention, according to the AUC. Less evidence supports SAVR with PCI. “Optimal management of coronary artery disease in patients with AS is a complex decision process requiring clinical, anatomical, and technical considerations that is best achieved with close collaboration between heart team members,” the authors stress.
The document covers other valvular and structural heart conditions that commonly accompany severe AS, such as symptomatic AS with bicuspid aortic valve and ascending aortic dilation. “Although there remains an increasing prevalence of transcatheter valve usage in bicuspid aortic valve, the standard of care remains surgical therapy, especially in patients who have a dilated aorta,” Dr. Thourani said.
For the first time, the AUC also addresses failing aortic valve prostheses, presenting six relevant clinical scenarios. The AUC consistently recommends SAVR, although the use of TAVR has “dramatically increased” in these patients, Dr. Thourani said. “Long-term data are still pending, but TAVR appears to be a less morbid procedure, when done appropriately.”
The societies involved in creating the AUC statement were the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.
Dr. Thourani disclosed ties to Edwards Lifesciences, St. Jude Medical, Abbott, Boston Scientific, and Medtronic.
New appropriate use criteria (AUC) for severe aortic stenosis (AS) run the full gamut of clinical scenarios and treatment options.
“Cardiology is seeing a radical change in the management of aortic stenosis. This new document incorporates all therapies currently available in the world,” said Vinod H. Thourani, MD, who served on the AUC’s writing group on behalf of the American College of Cardiology. “The AUC highlights state-of-the-art therapy for aortic stenosis and, even more importantly, helps clarify the right indications for surgical and transcatheter valve replacement.”
Surgical risk is assessed based on the Society of Thoracic Surgeons Predicted Risk of Mortality score plus additional anatomic and functional considerations that should be assessed by a multidisciplinary heart team. The AUC repeatedly emphasizes this team’s importance. “Multiple comorbidities can change the pathway of treating AS, and this determination is best made by a heart team that at least includes a noninvasive cardiologist, an interventional cardiologist, and a cardiac surgeon,” Dr. Thourani said. “That’s how patients get the best care.”
Historically, aortic stenosis typically was managed medically or with balloon aortic valvuloplasty (BAV) or open aortic valve replacement, Dr. Thourani said. However, BAV is less common now, and indications for surgical or transcatheter aortic valve replacement (SAVR or TAVR) are expanding. Balloon aortic valvuloplasty sometimes does provide palliative treatment or serve as a bridge to a decision, the AUC states. For example, for a high-risk patient with severe aortic stenosis and severe secondary mitral regurgitation, BAV can help the heart team decide whether TAVR alone will improve mitral regurgitation or whether a double valve procedure is preferable.
Regardless of risk score, the AUC considers a wait-and-see approach as potentially appropriate for patients with asymptomatic high-grade AS whose left ventricular ejection fraction is at least 50%, peak aortic valve velocity is 4.0-4.9 m/sec, and exercise stress test is normal and with no predictors of symptom onset or rapid progression. Asymptomatic patients who are likely to become symptomatic but who have a low risk of sudden death are candidates for intervention (rated “appropriate”) or medical management (“may be appropriate”). In contrast, a positive stress test in an otherwise asymptomatic patient merits consideration of SAVR or TAVR regardless of surgical risk. The recommendations for asymptomatic patients reflect a lack of head-to-head trials in this population, Dr. Thourani said. “We don’t have good randomized data to show one therapy is better than another.”
Symptomatic, high-gradient, severe AS with associated coronary artery disease merits consideration of SAVR with coronary artery bypass graft or, in some cases, TAVR with percutaneous coronary intervention, according to the AUC. Less evidence supports SAVR with PCI. “Optimal management of coronary artery disease in patients with AS is a complex decision process requiring clinical, anatomical, and technical considerations that is best achieved with close collaboration between heart team members,” the authors stress.
The document covers other valvular and structural heart conditions that commonly accompany severe AS, such as symptomatic AS with bicuspid aortic valve and ascending aortic dilation. “Although there remains an increasing prevalence of transcatheter valve usage in bicuspid aortic valve, the standard of care remains surgical therapy, especially in patients who have a dilated aorta,” Dr. Thourani said.
For the first time, the AUC also addresses failing aortic valve prostheses, presenting six relevant clinical scenarios. The AUC consistently recommends SAVR, although the use of TAVR has “dramatically increased” in these patients, Dr. Thourani said. “Long-term data are still pending, but TAVR appears to be a less morbid procedure, when done appropriately.”
The societies involved in creating the AUC statement were the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.
Dr. Thourani disclosed ties to Edwards Lifesciences, St. Jude Medical, Abbott, Boston Scientific, and Medtronic.
New appropriate use criteria (AUC) for severe aortic stenosis (AS) run the full gamut of clinical scenarios and treatment options.
“Cardiology is seeing a radical change in the management of aortic stenosis. This new document incorporates all therapies currently available in the world,” said Vinod H. Thourani, MD, who served on the AUC’s writing group on behalf of the American College of Cardiology. “The AUC highlights state-of-the-art therapy for aortic stenosis and, even more importantly, helps clarify the right indications for surgical and transcatheter valve replacement.”
Surgical risk is assessed based on the Society of Thoracic Surgeons Predicted Risk of Mortality score plus additional anatomic and functional considerations that should be assessed by a multidisciplinary heart team. The AUC repeatedly emphasizes this team’s importance. “Multiple comorbidities can change the pathway of treating AS, and this determination is best made by a heart team that at least includes a noninvasive cardiologist, an interventional cardiologist, and a cardiac surgeon,” Dr. Thourani said. “That’s how patients get the best care.”
Historically, aortic stenosis typically was managed medically or with balloon aortic valvuloplasty (BAV) or open aortic valve replacement, Dr. Thourani said. However, BAV is less common now, and indications for surgical or transcatheter aortic valve replacement (SAVR or TAVR) are expanding. Balloon aortic valvuloplasty sometimes does provide palliative treatment or serve as a bridge to a decision, the AUC states. For example, for a high-risk patient with severe aortic stenosis and severe secondary mitral regurgitation, BAV can help the heart team decide whether TAVR alone will improve mitral regurgitation or whether a double valve procedure is preferable.
Regardless of risk score, the AUC considers a wait-and-see approach as potentially appropriate for patients with asymptomatic high-grade AS whose left ventricular ejection fraction is at least 50%, peak aortic valve velocity is 4.0-4.9 m/sec, and exercise stress test is normal and with no predictors of symptom onset or rapid progression. Asymptomatic patients who are likely to become symptomatic but who have a low risk of sudden death are candidates for intervention (rated “appropriate”) or medical management (“may be appropriate”). In contrast, a positive stress test in an otherwise asymptomatic patient merits consideration of SAVR or TAVR regardless of surgical risk. The recommendations for asymptomatic patients reflect a lack of head-to-head trials in this population, Dr. Thourani said. “We don’t have good randomized data to show one therapy is better than another.”
Symptomatic, high-gradient, severe AS with associated coronary artery disease merits consideration of SAVR with coronary artery bypass graft or, in some cases, TAVR with percutaneous coronary intervention, according to the AUC. Less evidence supports SAVR with PCI. “Optimal management of coronary artery disease in patients with AS is a complex decision process requiring clinical, anatomical, and technical considerations that is best achieved with close collaboration between heart team members,” the authors stress.
The document covers other valvular and structural heart conditions that commonly accompany severe AS, such as symptomatic AS with bicuspid aortic valve and ascending aortic dilation. “Although there remains an increasing prevalence of transcatheter valve usage in bicuspid aortic valve, the standard of care remains surgical therapy, especially in patients who have a dilated aorta,” Dr. Thourani said.
For the first time, the AUC also addresses failing aortic valve prostheses, presenting six relevant clinical scenarios. The AUC consistently recommends SAVR, although the use of TAVR has “dramatically increased” in these patients, Dr. Thourani said. “Long-term data are still pending, but TAVR appears to be a less morbid procedure, when done appropriately.”
The societies involved in creating the AUC statement were the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.
Dr. Thourani disclosed ties to Edwards Lifesciences, St. Jude Medical, Abbott, Boston Scientific, and Medtronic.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Role grows for heart failure patient-reported outcomes
DALLAS – The Food and Drug Administration is keenly seeking patient-reported outcomes as endpoints in cardiovascular drug or device trials, particularly for heart failure patients, but the bar remains high for getting such an outcome into labeling, said agency officials who regulate cardiovascular disease therapies.
The FDA issued guidance nearly 8 years ago on how to integrate patient-reported outcome (PRO) measures into medical product development, but so far no heart failure drug nor device has met the agency’s standards for documented success in improving a PRO, despite the clear need for these patients to receive patient-centered care, clinicians said.
“We don’t yet have a patient-reported outcome in a label for heart failure,” Paul A. Heidenreich, MD, said during a session on PROs at the annual scientific meeting of the Heart Failure Society of America. He voiced hope that a PRO might end up on the label of a heart failure drug or device sometime in 2018. “Almost half of FDA submissions now include a PRO” as part of the data package, added Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University.
For years, PROs for heart failure weren’t often used in trials, and they remain largely absent from routine practice – an absence Dr. Heidenreich lamented. “Just focusing on mortality in heart failure is really not patient centered,” he said.
Heart failure physicians “are very good at disease-centered care” that focuses on survival and reducing hospitalizations, but “survival is often not as important to patients,” noted Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation program at St. Vincent Medical Group in Indianapolis. She suggested “tailoring treatment to improve patient symptoms, physical function, and quality of life” without necessarily reducing hospital readmissions or increasing survival rates. “Self-reported measures have more meaning for patients,” she said, and called for using PROs to better target interventions to the patients who can most benefit from them.
Two FDA representatives who spoke during the session agreed on the importance of PROs and attested to the agency’s interest in greater reliance on them.
“PROs are a critical complement to the other measures made in device trials,” said Bram Zuckerman, MD, director of the FDA’s division of cardiovascular devices. “We need PRO information because it reflects important aspects of patients’ health-related quality of life.”
The most commonly used PRO measures in device trials today are the Kansas City Cardiomyopathy Questionnaire (J Am Coll Cardiol. 2000 Apr;35[5]:1245-55) and the Minnesota Living With Heart Failure questionnaire, he noted.
“Neither is perfect, but there is a track record in heart failure device development that these two PROs can be helpful.” The FDA’s cardiovascular device division “wants to use PRO information,” Dr. Zuckerman said.
“All-cause mortality is the most unbiased endpoint, but there is interest in PROs,” agreed Ebony Dashiell-Aje, PhD, from the FDA’s office of new drugs in the Center for Drug Evaluation and Research. She highlighted the encouragement that the FDA gave to drug and device developers to include PROs in trials, both in its 2009 guidance document as well as in a “roadmap” from the agency on how to measure PROs in clinical trials. “Unfortunately, in heart failure we struggle to find tools that can adequately measure the patient’s perspective and be sensitive enough to detect a treatment benefit,” she said.
Norman Stockbridge, MD, director of the division of cardiovascular and renal products in the agency’s Office of Drug Evaluation, cited even bigger barriers to FDA approval of PROs as labeled effects from drugs or devices.
Getting a PRO endpoint supported by clinical-trial results that qualify it for an FDA label faces two big challenges. One challenge, he said, is “how much of an effect we need to see in a complex scoring algorithm to know that patients actually received some benefit in a disease that often varies from day to day and from week to week.” The second challenge is that, “in a disease with a high background rate of bad outcomes, you need some evidence that the benefit [from the treatment] is worth any risk,” which is something that can be hard to prove in heart failure when many patients don’t live more than 2 years with the disease, Dr. Stockbridge said in an interview.
“You need to be able to make the argument that the [PRO] benefit is likely perceptible to patients, but that is only half the problem. The other half is whether the developer can rule out that survival is not less than it would have been with no treatment. If patients take this, will they feel better but have a greater risk of being hurt?”
So far, no drug or device developer has succeeded in proving this to the FDA, despite the agency’s 2009 guidance on how it could be done.
That guidance “is one of the two worst and most destructive guidance documents we ever published,” Dr. Stockbridge declared.
Dr. Walsh, Dr. Heidenreich, Dr. Zuckerman, Dr. Dashiell-Aje, and Dr. Stockbridge had no relevant disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
DALLAS – The Food and Drug Administration is keenly seeking patient-reported outcomes as endpoints in cardiovascular drug or device trials, particularly for heart failure patients, but the bar remains high for getting such an outcome into labeling, said agency officials who regulate cardiovascular disease therapies.
The FDA issued guidance nearly 8 years ago on how to integrate patient-reported outcome (PRO) measures into medical product development, but so far no heart failure drug nor device has met the agency’s standards for documented success in improving a PRO, despite the clear need for these patients to receive patient-centered care, clinicians said.
“We don’t yet have a patient-reported outcome in a label for heart failure,” Paul A. Heidenreich, MD, said during a session on PROs at the annual scientific meeting of the Heart Failure Society of America. He voiced hope that a PRO might end up on the label of a heart failure drug or device sometime in 2018. “Almost half of FDA submissions now include a PRO” as part of the data package, added Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University.
For years, PROs for heart failure weren’t often used in trials, and they remain largely absent from routine practice – an absence Dr. Heidenreich lamented. “Just focusing on mortality in heart failure is really not patient centered,” he said.
Heart failure physicians “are very good at disease-centered care” that focuses on survival and reducing hospitalizations, but “survival is often not as important to patients,” noted Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation program at St. Vincent Medical Group in Indianapolis. She suggested “tailoring treatment to improve patient symptoms, physical function, and quality of life” without necessarily reducing hospital readmissions or increasing survival rates. “Self-reported measures have more meaning for patients,” she said, and called for using PROs to better target interventions to the patients who can most benefit from them.
Two FDA representatives who spoke during the session agreed on the importance of PROs and attested to the agency’s interest in greater reliance on them.
“PROs are a critical complement to the other measures made in device trials,” said Bram Zuckerman, MD, director of the FDA’s division of cardiovascular devices. “We need PRO information because it reflects important aspects of patients’ health-related quality of life.”
The most commonly used PRO measures in device trials today are the Kansas City Cardiomyopathy Questionnaire (J Am Coll Cardiol. 2000 Apr;35[5]:1245-55) and the Minnesota Living With Heart Failure questionnaire, he noted.
“Neither is perfect, but there is a track record in heart failure device development that these two PROs can be helpful.” The FDA’s cardiovascular device division “wants to use PRO information,” Dr. Zuckerman said.
“All-cause mortality is the most unbiased endpoint, but there is interest in PROs,” agreed Ebony Dashiell-Aje, PhD, from the FDA’s office of new drugs in the Center for Drug Evaluation and Research. She highlighted the encouragement that the FDA gave to drug and device developers to include PROs in trials, both in its 2009 guidance document as well as in a “roadmap” from the agency on how to measure PROs in clinical trials. “Unfortunately, in heart failure we struggle to find tools that can adequately measure the patient’s perspective and be sensitive enough to detect a treatment benefit,” she said.
Norman Stockbridge, MD, director of the division of cardiovascular and renal products in the agency’s Office of Drug Evaluation, cited even bigger barriers to FDA approval of PROs as labeled effects from drugs or devices.
Getting a PRO endpoint supported by clinical-trial results that qualify it for an FDA label faces two big challenges. One challenge, he said, is “how much of an effect we need to see in a complex scoring algorithm to know that patients actually received some benefit in a disease that often varies from day to day and from week to week.” The second challenge is that, “in a disease with a high background rate of bad outcomes, you need some evidence that the benefit [from the treatment] is worth any risk,” which is something that can be hard to prove in heart failure when many patients don’t live more than 2 years with the disease, Dr. Stockbridge said in an interview.
“You need to be able to make the argument that the [PRO] benefit is likely perceptible to patients, but that is only half the problem. The other half is whether the developer can rule out that survival is not less than it would have been with no treatment. If patients take this, will they feel better but have a greater risk of being hurt?”
So far, no drug or device developer has succeeded in proving this to the FDA, despite the agency’s 2009 guidance on how it could be done.
That guidance “is one of the two worst and most destructive guidance documents we ever published,” Dr. Stockbridge declared.
Dr. Walsh, Dr. Heidenreich, Dr. Zuckerman, Dr. Dashiell-Aje, and Dr. Stockbridge had no relevant disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
DALLAS – The Food and Drug Administration is keenly seeking patient-reported outcomes as endpoints in cardiovascular drug or device trials, particularly for heart failure patients, but the bar remains high for getting such an outcome into labeling, said agency officials who regulate cardiovascular disease therapies.
The FDA issued guidance nearly 8 years ago on how to integrate patient-reported outcome (PRO) measures into medical product development, but so far no heart failure drug nor device has met the agency’s standards for documented success in improving a PRO, despite the clear need for these patients to receive patient-centered care, clinicians said.
“We don’t yet have a patient-reported outcome in a label for heart failure,” Paul A. Heidenreich, MD, said during a session on PROs at the annual scientific meeting of the Heart Failure Society of America. He voiced hope that a PRO might end up on the label of a heart failure drug or device sometime in 2018. “Almost half of FDA submissions now include a PRO” as part of the data package, added Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University.
For years, PROs for heart failure weren’t often used in trials, and they remain largely absent from routine practice – an absence Dr. Heidenreich lamented. “Just focusing on mortality in heart failure is really not patient centered,” he said.
Heart failure physicians “are very good at disease-centered care” that focuses on survival and reducing hospitalizations, but “survival is often not as important to patients,” noted Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation program at St. Vincent Medical Group in Indianapolis. She suggested “tailoring treatment to improve patient symptoms, physical function, and quality of life” without necessarily reducing hospital readmissions or increasing survival rates. “Self-reported measures have more meaning for patients,” she said, and called for using PROs to better target interventions to the patients who can most benefit from them.
Two FDA representatives who spoke during the session agreed on the importance of PROs and attested to the agency’s interest in greater reliance on them.
“PROs are a critical complement to the other measures made in device trials,” said Bram Zuckerman, MD, director of the FDA’s division of cardiovascular devices. “We need PRO information because it reflects important aspects of patients’ health-related quality of life.”
The most commonly used PRO measures in device trials today are the Kansas City Cardiomyopathy Questionnaire (J Am Coll Cardiol. 2000 Apr;35[5]:1245-55) and the Minnesota Living With Heart Failure questionnaire, he noted.
“Neither is perfect, but there is a track record in heart failure device development that these two PROs can be helpful.” The FDA’s cardiovascular device division “wants to use PRO information,” Dr. Zuckerman said.
“All-cause mortality is the most unbiased endpoint, but there is interest in PROs,” agreed Ebony Dashiell-Aje, PhD, from the FDA’s office of new drugs in the Center for Drug Evaluation and Research. She highlighted the encouragement that the FDA gave to drug and device developers to include PROs in trials, both in its 2009 guidance document as well as in a “roadmap” from the agency on how to measure PROs in clinical trials. “Unfortunately, in heart failure we struggle to find tools that can adequately measure the patient’s perspective and be sensitive enough to detect a treatment benefit,” she said.
Norman Stockbridge, MD, director of the division of cardiovascular and renal products in the agency’s Office of Drug Evaluation, cited even bigger barriers to FDA approval of PROs as labeled effects from drugs or devices.
Getting a PRO endpoint supported by clinical-trial results that qualify it for an FDA label faces two big challenges. One challenge, he said, is “how much of an effect we need to see in a complex scoring algorithm to know that patients actually received some benefit in a disease that often varies from day to day and from week to week.” The second challenge is that, “in a disease with a high background rate of bad outcomes, you need some evidence that the benefit [from the treatment] is worth any risk,” which is something that can be hard to prove in heart failure when many patients don’t live more than 2 years with the disease, Dr. Stockbridge said in an interview.
“You need to be able to make the argument that the [PRO] benefit is likely perceptible to patients, but that is only half the problem. The other half is whether the developer can rule out that survival is not less than it would have been with no treatment. If patients take this, will they feel better but have a greater risk of being hurt?”
So far, no drug or device developer has succeeded in proving this to the FDA, despite the agency’s 2009 guidance on how it could be done.
That guidance “is one of the two worst and most destructive guidance documents we ever published,” Dr. Stockbridge declared.
Dr. Walsh, Dr. Heidenreich, Dr. Zuckerman, Dr. Dashiell-Aje, and Dr. Stockbridge had no relevant disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE HFSA ANNUAL SCIENTIFIC MEETING
CardioMEMS shows real-world success as use expands
DALLAS – Management of outpatients with advanced heart failure using an implanted pulmonary artery pressure monitor continues to show real-world efficacy and safety at least as impressive as in the pivotal trial for the device.
Data from the first waves of patients to receive the CardioMEMS implanted pulmonary artery pressure (PAP) monitor since it got Food and Drug Administration marketing approval in May 2014 also showed steady uptake of this fluid volume management strategy for patients with advanced heart failure, despite Medicare reimbursement issues in some U.S. regions, J. Thomas Heywood, MD, said at the at the annual scientific meeting of the Heart Failure Society of America. He estimated that more than 6,000 U.S. heart failure patients have now had a CardioMEMS PAP monitor implanted.
“The clinicians using CardioMEMS now have a lot more experience” than they had during the trial, he said in an interview. “They have more experience using the device, they know what treatments to use to lower PAP more effectively, and they are now convinced that patients will benefit from reducing diastolic PAP.”
Dr. Heywood estimated that tens of thousands more U.S. heart failure patients with New York Heart Association class III disease and a recent history of at least one heart failure hospitalization are eligible to receive an implanted PAP monitor, dwarfing the more than 6,000 patients who received a device so far.
The postapproval study
The newest efficacy data come from the first 300 patients enrolled in the CardioMEMS HF System Post Approval Study, a registry of patients receiving an implanted PAP monitor funded by the device’s manufacturer and scheduled to include a total of 1,200 patients. Dr. Heywood said full enrollment was on track for completion by the end of October 2017.
The first 300 patients enrolled in the postapproval study were older than the CHAMPION cohort; they averaged about 69 years of age, compared with about 62 years in CHAMPION, were more often women (38% vs. 28% in CHAMPION), and were more likely to have heart failure with preserved ejection fraction (41% vs. about 22%).
A similar pattern existed for the 6-month cumulative tally of PAP area under the curve, which showed an average rise of 42 mm Hg/day in the CHAMPION control patients, an average drop of 160 mm Hg/day in the CHAMPION patients managed using their CardioMEMS data, and a drop of 281 mm Hg/day in the 300 postapproval study patients.
“We’re now using the implanted sensor in a broader population of patients, and one wonders whether the effect will be diluted. What we see is at least as good as in the CHAMPION trial. This is just an early snapshot, but it is exciting that we see no erosion of the benefit. It’s a great indication that the correct patients are receiving it,” Dr. Raval said while presenting a poster at the meeting.
Further scrutiny of the same 300 patients showed another feature of the impact of PAP monitoring on patient outcomes: The first 90 days with the PAP monitor in place led to a greater number of tweaks in patient treatment and a steady fall in PAP. During days 91-180, PAP tended to level off, the number of medication adjustments dropped, and heart failure hospitalizations fell even more than in the first 90 days, Joanna M. Joly, MD, reported in a separate poster at the meeting.
The data showed “effective reduction” of PAP during the second half of the study despite fewer medication adjustments. How was that possible? Patients who transmit data on their PAPs undergo “modeling of their behavior” based on the feedback they receive from the device, Dr. Joly suggested. Regular measurement of their PAP and seeing how the number relates to their clinical status helps patients “understand the impact of their nonadherence to diet and their medications.” Another factor could be the growing familiarity clinicians develop over time with PAP fluctuations that individual patients display repeatedly that are usually self-correcting. Also, patients may undergo “hemodynamic remodeling” that results in improved self-correction of minor shifts in fluid volume and vascular tone, she said.
This pattern of a reduced need for interventions after the first 90 days with a PAP implant suggests that many patients managed this way may be able to transition to care largely delivered by local providers, or even play a greater role in their own self-care once their PAP and clinical state stabilizes, Dr. Joly said.
The findings imply that by the end of the first 90 days, “patients accept the device and manage themselves better. It becomes basically a behavioral device” that helps patients better optimize their diet and behavior, Dr. Raval observed.
Safety holds steady
Continued real-world use of PAP monitoring has also resulted in new safety insights. During the first 3 years when the CardioMEMS device was on the U.S. market, May 2014–May 2017, the FDA’s adverse event reporting system for devices, the Manufacturer and User Facility Device Experience (MAUDE) received reports on 177 unique adverse events in 155 patients implanted with a PAP monitor, Muthiah Vaduganathan, MD, reported at the meeting. During the same 3-year period, he estimated that at least 5,500 U.S. patients had received a CardioMEMS device, based on data Dr. Vaduganathan obtained from the manufacturer, Abbott. This works out to an adverse event rate of about 2.8%, virtually identical to the rate reported from CHAMPION, noted Dr. Vaduganathan, a cardiologist also at Brigham and Women’s.
Analysis of both the 22 deaths as well as the episodes of pulmonary artery injury or hemoptysis showed that the preponderance occurred relatively early after introduction for U.S. use, suggesting that “a learning curve may exist for the most serious complications,” he said. “Improved safety and device durability may result from careful patient selection, increased operator training, and refined technologies.”
Dr. Vaduganathan cautioned that the MAUDE database is limited by its bias toward serious adverse events, selective reporting, and lack of adjudication for the reported events. Concurrently with his report at the meeting, a written version appeared online (JAMA Cardiol. 2017 Sep 18. doi:10.1001/jamacardio.2017.3791).
“The adverse event rate was reassuringly low, well below the accepted threshold for device safety. It bodes favorably for the device,” he said in an interview.
“But with a passive surveillance system like MAUDE, adverse events are likely underreported; we see in MAUDE the most severe adverse events. There is certainly a larger spectrum of more minor events that we are not seeing, but I think these numbers accurately reflect serious events.” A full registry of every U.S. patient who receives the device, similar to what’s in place for U.S. patients who undergo transcatheter aortic valve replacement, would provide a more complete picture of the risks, Dr. Vaduganathan suggested.
He also voiced some surprise about the frequency of pulmonary artery injury, which was not as apparent in the 550 total patients enrolled in CHAMPION. Clinicians who place the PAP monitor are required to first take a training program, but the manufacturer has no mandated minimum number of placements an operator must assist on before launching a new CardioMEMS practice, Dr. Vaduganathan said. Many of the pulmonary artery injuries reported to MAUDE resulted from wire perforations that resulted from loss of wire control, he noted.
Clarifying the optimal CardioMEMS recipients
PAP monitoring for patients with advanced heart failure “is a major advance for certain patients who have historically been very challenging to manage,” especially patients with heart failure with preserved ejection fraction, which has few other treatment options. But “it’s often difficult to know when to pull the trigger” and proceed with placing a PAP monitor in an eligible patient, he said. “Greater experience will help us better understand that,” Dr. Vaduganathan predicted.
Dr. Heywood said that, in addition to the standard criteria of NYHA class III symptoms and a recent history of a heart failure hospitalization, the other clinical feature he looks for in a patient who is a possible CardioMEMS recipient is a persistently elevated systolic PAP as measured using echocardiography.
“These are patients with evidence of an ongoing hemodynamic problem despite treatment, and I need more data to do a better job of getting their PAP down.” Although the PAP that patients self-measure once they have the device in place is their diastolic PAP, measuring systolic PAP by echo is usually a good surrogate for finding patients who also have a persistently elevated diastolic PAP, he explained.
Another important selection criterion is to look for the patients who are dying from heart failure rather than with heart failure, Dr. Heywood added.
“If heart failure is the major thing wrong, then we can improve their quality of life” by guiding fluid management with regular PAP measurement, especially patients with preserved left ventricular ejection fraction who have few other treatment options right now, he said.
The CardioMEMS HF System Post Approval Study is sponsored by Abbott, which markets CardioMEMS. Dr Heywood has been a consultant to and/or has received research funding from Abbott as well as Impedimed, Medtronic, Novartis, and Otsuka. Dr. Raval has been a consultant to Abbott. Dr. Joly and Dr. Vaduganathan had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
DALLAS – Management of outpatients with advanced heart failure using an implanted pulmonary artery pressure monitor continues to show real-world efficacy and safety at least as impressive as in the pivotal trial for the device.
Data from the first waves of patients to receive the CardioMEMS implanted pulmonary artery pressure (PAP) monitor since it got Food and Drug Administration marketing approval in May 2014 also showed steady uptake of this fluid volume management strategy for patients with advanced heart failure, despite Medicare reimbursement issues in some U.S. regions, J. Thomas Heywood, MD, said at the at the annual scientific meeting of the Heart Failure Society of America. He estimated that more than 6,000 U.S. heart failure patients have now had a CardioMEMS PAP monitor implanted.
“The clinicians using CardioMEMS now have a lot more experience” than they had during the trial, he said in an interview. “They have more experience using the device, they know what treatments to use to lower PAP more effectively, and they are now convinced that patients will benefit from reducing diastolic PAP.”
Dr. Heywood estimated that tens of thousands more U.S. heart failure patients with New York Heart Association class III disease and a recent history of at least one heart failure hospitalization are eligible to receive an implanted PAP monitor, dwarfing the more than 6,000 patients who received a device so far.
The postapproval study
The newest efficacy data come from the first 300 patients enrolled in the CardioMEMS HF System Post Approval Study, a registry of patients receiving an implanted PAP monitor funded by the device’s manufacturer and scheduled to include a total of 1,200 patients. Dr. Heywood said full enrollment was on track for completion by the end of October 2017.
The first 300 patients enrolled in the postapproval study were older than the CHAMPION cohort; they averaged about 69 years of age, compared with about 62 years in CHAMPION, were more often women (38% vs. 28% in CHAMPION), and were more likely to have heart failure with preserved ejection fraction (41% vs. about 22%).
A similar pattern existed for the 6-month cumulative tally of PAP area under the curve, which showed an average rise of 42 mm Hg/day in the CHAMPION control patients, an average drop of 160 mm Hg/day in the CHAMPION patients managed using their CardioMEMS data, and a drop of 281 mm Hg/day in the 300 postapproval study patients.
“We’re now using the implanted sensor in a broader population of patients, and one wonders whether the effect will be diluted. What we see is at least as good as in the CHAMPION trial. This is just an early snapshot, but it is exciting that we see no erosion of the benefit. It’s a great indication that the correct patients are receiving it,” Dr. Raval said while presenting a poster at the meeting.
Further scrutiny of the same 300 patients showed another feature of the impact of PAP monitoring on patient outcomes: The first 90 days with the PAP monitor in place led to a greater number of tweaks in patient treatment and a steady fall in PAP. During days 91-180, PAP tended to level off, the number of medication adjustments dropped, and heart failure hospitalizations fell even more than in the first 90 days, Joanna M. Joly, MD, reported in a separate poster at the meeting.
The data showed “effective reduction” of PAP during the second half of the study despite fewer medication adjustments. How was that possible? Patients who transmit data on their PAPs undergo “modeling of their behavior” based on the feedback they receive from the device, Dr. Joly suggested. Regular measurement of their PAP and seeing how the number relates to their clinical status helps patients “understand the impact of their nonadherence to diet and their medications.” Another factor could be the growing familiarity clinicians develop over time with PAP fluctuations that individual patients display repeatedly that are usually self-correcting. Also, patients may undergo “hemodynamic remodeling” that results in improved self-correction of minor shifts in fluid volume and vascular tone, she said.
This pattern of a reduced need for interventions after the first 90 days with a PAP implant suggests that many patients managed this way may be able to transition to care largely delivered by local providers, or even play a greater role in their own self-care once their PAP and clinical state stabilizes, Dr. Joly said.
The findings imply that by the end of the first 90 days, “patients accept the device and manage themselves better. It becomes basically a behavioral device” that helps patients better optimize their diet and behavior, Dr. Raval observed.
Safety holds steady
Continued real-world use of PAP monitoring has also resulted in new safety insights. During the first 3 years when the CardioMEMS device was on the U.S. market, May 2014–May 2017, the FDA’s adverse event reporting system for devices, the Manufacturer and User Facility Device Experience (MAUDE) received reports on 177 unique adverse events in 155 patients implanted with a PAP monitor, Muthiah Vaduganathan, MD, reported at the meeting. During the same 3-year period, he estimated that at least 5,500 U.S. patients had received a CardioMEMS device, based on data Dr. Vaduganathan obtained from the manufacturer, Abbott. This works out to an adverse event rate of about 2.8%, virtually identical to the rate reported from CHAMPION, noted Dr. Vaduganathan, a cardiologist also at Brigham and Women’s.
Analysis of both the 22 deaths as well as the episodes of pulmonary artery injury or hemoptysis showed that the preponderance occurred relatively early after introduction for U.S. use, suggesting that “a learning curve may exist for the most serious complications,” he said. “Improved safety and device durability may result from careful patient selection, increased operator training, and refined technologies.”
Dr. Vaduganathan cautioned that the MAUDE database is limited by its bias toward serious adverse events, selective reporting, and lack of adjudication for the reported events. Concurrently with his report at the meeting, a written version appeared online (JAMA Cardiol. 2017 Sep 18. doi:10.1001/jamacardio.2017.3791).
“The adverse event rate was reassuringly low, well below the accepted threshold for device safety. It bodes favorably for the device,” he said in an interview.
“But with a passive surveillance system like MAUDE, adverse events are likely underreported; we see in MAUDE the most severe adverse events. There is certainly a larger spectrum of more minor events that we are not seeing, but I think these numbers accurately reflect serious events.” A full registry of every U.S. patient who receives the device, similar to what’s in place for U.S. patients who undergo transcatheter aortic valve replacement, would provide a more complete picture of the risks, Dr. Vaduganathan suggested.
He also voiced some surprise about the frequency of pulmonary artery injury, which was not as apparent in the 550 total patients enrolled in CHAMPION. Clinicians who place the PAP monitor are required to first take a training program, but the manufacturer has no mandated minimum number of placements an operator must assist on before launching a new CardioMEMS practice, Dr. Vaduganathan said. Many of the pulmonary artery injuries reported to MAUDE resulted from wire perforations that resulted from loss of wire control, he noted.
Clarifying the optimal CardioMEMS recipients
PAP monitoring for patients with advanced heart failure “is a major advance for certain patients who have historically been very challenging to manage,” especially patients with heart failure with preserved ejection fraction, which has few other treatment options. But “it’s often difficult to know when to pull the trigger” and proceed with placing a PAP monitor in an eligible patient, he said. “Greater experience will help us better understand that,” Dr. Vaduganathan predicted.
Dr. Heywood said that, in addition to the standard criteria of NYHA class III symptoms and a recent history of a heart failure hospitalization, the other clinical feature he looks for in a patient who is a possible CardioMEMS recipient is a persistently elevated systolic PAP as measured using echocardiography.
“These are patients with evidence of an ongoing hemodynamic problem despite treatment, and I need more data to do a better job of getting their PAP down.” Although the PAP that patients self-measure once they have the device in place is their diastolic PAP, measuring systolic PAP by echo is usually a good surrogate for finding patients who also have a persistently elevated diastolic PAP, he explained.
Another important selection criterion is to look for the patients who are dying from heart failure rather than with heart failure, Dr. Heywood added.
“If heart failure is the major thing wrong, then we can improve their quality of life” by guiding fluid management with regular PAP measurement, especially patients with preserved left ventricular ejection fraction who have few other treatment options right now, he said.
The CardioMEMS HF System Post Approval Study is sponsored by Abbott, which markets CardioMEMS. Dr Heywood has been a consultant to and/or has received research funding from Abbott as well as Impedimed, Medtronic, Novartis, and Otsuka. Dr. Raval has been a consultant to Abbott. Dr. Joly and Dr. Vaduganathan had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
DALLAS – Management of outpatients with advanced heart failure using an implanted pulmonary artery pressure monitor continues to show real-world efficacy and safety at least as impressive as in the pivotal trial for the device.
Data from the first waves of patients to receive the CardioMEMS implanted pulmonary artery pressure (PAP) monitor since it got Food and Drug Administration marketing approval in May 2014 also showed steady uptake of this fluid volume management strategy for patients with advanced heart failure, despite Medicare reimbursement issues in some U.S. regions, J. Thomas Heywood, MD, said at the at the annual scientific meeting of the Heart Failure Society of America. He estimated that more than 6,000 U.S. heart failure patients have now had a CardioMEMS PAP monitor implanted.
“The clinicians using CardioMEMS now have a lot more experience” than they had during the trial, he said in an interview. “They have more experience using the device, they know what treatments to use to lower PAP more effectively, and they are now convinced that patients will benefit from reducing diastolic PAP.”
Dr. Heywood estimated that tens of thousands more U.S. heart failure patients with New York Heart Association class III disease and a recent history of at least one heart failure hospitalization are eligible to receive an implanted PAP monitor, dwarfing the more than 6,000 patients who received a device so far.
The postapproval study
The newest efficacy data come from the first 300 patients enrolled in the CardioMEMS HF System Post Approval Study, a registry of patients receiving an implanted PAP monitor funded by the device’s manufacturer and scheduled to include a total of 1,200 patients. Dr. Heywood said full enrollment was on track for completion by the end of October 2017.
The first 300 patients enrolled in the postapproval study were older than the CHAMPION cohort; they averaged about 69 years of age, compared with about 62 years in CHAMPION, were more often women (38% vs. 28% in CHAMPION), and were more likely to have heart failure with preserved ejection fraction (41% vs. about 22%).
A similar pattern existed for the 6-month cumulative tally of PAP area under the curve, which showed an average rise of 42 mm Hg/day in the CHAMPION control patients, an average drop of 160 mm Hg/day in the CHAMPION patients managed using their CardioMEMS data, and a drop of 281 mm Hg/day in the 300 postapproval study patients.
“We’re now using the implanted sensor in a broader population of patients, and one wonders whether the effect will be diluted. What we see is at least as good as in the CHAMPION trial. This is just an early snapshot, but it is exciting that we see no erosion of the benefit. It’s a great indication that the correct patients are receiving it,” Dr. Raval said while presenting a poster at the meeting.
Further scrutiny of the same 300 patients showed another feature of the impact of PAP monitoring on patient outcomes: The first 90 days with the PAP monitor in place led to a greater number of tweaks in patient treatment and a steady fall in PAP. During days 91-180, PAP tended to level off, the number of medication adjustments dropped, and heart failure hospitalizations fell even more than in the first 90 days, Joanna M. Joly, MD, reported in a separate poster at the meeting.
The data showed “effective reduction” of PAP during the second half of the study despite fewer medication adjustments. How was that possible? Patients who transmit data on their PAPs undergo “modeling of their behavior” based on the feedback they receive from the device, Dr. Joly suggested. Regular measurement of their PAP and seeing how the number relates to their clinical status helps patients “understand the impact of their nonadherence to diet and their medications.” Another factor could be the growing familiarity clinicians develop over time with PAP fluctuations that individual patients display repeatedly that are usually self-correcting. Also, patients may undergo “hemodynamic remodeling” that results in improved self-correction of minor shifts in fluid volume and vascular tone, she said.
This pattern of a reduced need for interventions after the first 90 days with a PAP implant suggests that many patients managed this way may be able to transition to care largely delivered by local providers, or even play a greater role in their own self-care once their PAP and clinical state stabilizes, Dr. Joly said.
The findings imply that by the end of the first 90 days, “patients accept the device and manage themselves better. It becomes basically a behavioral device” that helps patients better optimize their diet and behavior, Dr. Raval observed.
Safety holds steady
Continued real-world use of PAP monitoring has also resulted in new safety insights. During the first 3 years when the CardioMEMS device was on the U.S. market, May 2014–May 2017, the FDA’s adverse event reporting system for devices, the Manufacturer and User Facility Device Experience (MAUDE) received reports on 177 unique adverse events in 155 patients implanted with a PAP monitor, Muthiah Vaduganathan, MD, reported at the meeting. During the same 3-year period, he estimated that at least 5,500 U.S. patients had received a CardioMEMS device, based on data Dr. Vaduganathan obtained from the manufacturer, Abbott. This works out to an adverse event rate of about 2.8%, virtually identical to the rate reported from CHAMPION, noted Dr. Vaduganathan, a cardiologist also at Brigham and Women’s.
Analysis of both the 22 deaths as well as the episodes of pulmonary artery injury or hemoptysis showed that the preponderance occurred relatively early after introduction for U.S. use, suggesting that “a learning curve may exist for the most serious complications,” he said. “Improved safety and device durability may result from careful patient selection, increased operator training, and refined technologies.”
Dr. Vaduganathan cautioned that the MAUDE database is limited by its bias toward serious adverse events, selective reporting, and lack of adjudication for the reported events. Concurrently with his report at the meeting, a written version appeared online (JAMA Cardiol. 2017 Sep 18. doi:10.1001/jamacardio.2017.3791).
“The adverse event rate was reassuringly low, well below the accepted threshold for device safety. It bodes favorably for the device,” he said in an interview.
“But with a passive surveillance system like MAUDE, adverse events are likely underreported; we see in MAUDE the most severe adverse events. There is certainly a larger spectrum of more minor events that we are not seeing, but I think these numbers accurately reflect serious events.” A full registry of every U.S. patient who receives the device, similar to what’s in place for U.S. patients who undergo transcatheter aortic valve replacement, would provide a more complete picture of the risks, Dr. Vaduganathan suggested.
He also voiced some surprise about the frequency of pulmonary artery injury, which was not as apparent in the 550 total patients enrolled in CHAMPION. Clinicians who place the PAP monitor are required to first take a training program, but the manufacturer has no mandated minimum number of placements an operator must assist on before launching a new CardioMEMS practice, Dr. Vaduganathan said. Many of the pulmonary artery injuries reported to MAUDE resulted from wire perforations that resulted from loss of wire control, he noted.
Clarifying the optimal CardioMEMS recipients
PAP monitoring for patients with advanced heart failure “is a major advance for certain patients who have historically been very challenging to manage,” especially patients with heart failure with preserved ejection fraction, which has few other treatment options. But “it’s often difficult to know when to pull the trigger” and proceed with placing a PAP monitor in an eligible patient, he said. “Greater experience will help us better understand that,” Dr. Vaduganathan predicted.
Dr. Heywood said that, in addition to the standard criteria of NYHA class III symptoms and a recent history of a heart failure hospitalization, the other clinical feature he looks for in a patient who is a possible CardioMEMS recipient is a persistently elevated systolic PAP as measured using echocardiography.
“These are patients with evidence of an ongoing hemodynamic problem despite treatment, and I need more data to do a better job of getting their PAP down.” Although the PAP that patients self-measure once they have the device in place is their diastolic PAP, measuring systolic PAP by echo is usually a good surrogate for finding patients who also have a persistently elevated diastolic PAP, he explained.
Another important selection criterion is to look for the patients who are dying from heart failure rather than with heart failure, Dr. Heywood added.
“If heart failure is the major thing wrong, then we can improve their quality of life” by guiding fluid management with regular PAP measurement, especially patients with preserved left ventricular ejection fraction who have few other treatment options right now, he said.
The CardioMEMS HF System Post Approval Study is sponsored by Abbott, which markets CardioMEMS. Dr Heywood has been a consultant to and/or has received research funding from Abbott as well as Impedimed, Medtronic, Novartis, and Otsuka. Dr. Raval has been a consultant to Abbott. Dr. Joly and Dr. Vaduganathan had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
MI, stroke risk from HFrEF surpasses HFpEF
DALLAS – Patients newly diagnosed with heart failure with reduced ejection fraction had about an 8% incidence of MIs during the subsequent 9 months, and a 5% incidence of ischemic strokes in a retrospective review of more than 1,600 community-dwelling U.S. patients.
The MI and ischemic stroke incidence rates in heart failure patients with reduced ejection fraction (HFrEF) were both significantly higher than in more than 4,000 patients with heart failure with preserved ejection fraction (HFpEF), Gregg C. Fonarow, MD, said while presenting a poster at the annual scientific meeting of the Heart Failure Society of America.
The findings suggest that greater attention is needed to reduce the risks for MI and stroke in HFrEF patients, suggested Dr. Fonarow, professor and cochief of cardiology at the University of California, Los Angeles, and his associates in their poster.
The study used claims data collected during July 2009-September 2016 from more than 10 million people enrolled in the United Health Group, who received care at more than 650 hospitals and about 6,600 clinics. The study included all patients diagnosed with heart failure during a hospital or emergency room visit and who had no history of a heart failure diagnosis or episode during the preceding 18 months, a left ventricular ejection fraction measurement made close to the time of the index encounter, and no stroke or MI apparent at the time of the index event. The study included 1,622 patients with HFrEF, defined as a left ventricular ejection fraction of less than 40%, 4,288 with HFpEF, defined as an ejection fraction of 50% or more, and 1,095 with heart failure with a borderline ejection fraction of 40%-49%.
The HFrEF patients had an average ejection fraction of 28%, they averaged 72 years old, 36% were women, and 8% had a prior stroke. The HFpEF patients averaged 74 years old, their average ejection fraction was 61%, 55% were women, and 11% had a prior stroke. Follow-up data on all patients were available for an average of nearly 9 months following their index heart failure event, with some patients followed as long as 1 year.
During follow-up, the incidence of ischemic stroke was 5.4% in the HFrEF patients and 3.9% in those with HFpEF, a difference that worked out to a statistically significant 40% higher ischemic stroke rate in HFrEF patients after adjustment for baseline differences between the two patient groups, Dr. Fonarow reported. The patients with a borderline ejection fraction had a 3.7% stroke incidence that fell short of a significant difference, compared with the HFrEF patient.The rate of new MIs during follow-up was 7.5% in the HFrEF patients and 3.2% in the HFpEF patients, a statistically significant 2.5-fold relatively higher MI rate with HFrEF, a statistically significant difference after adjustments. The MI incidence in patients with a borderline ejection fraction was 5.9%
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
DALLAS – Patients newly diagnosed with heart failure with reduced ejection fraction had about an 8% incidence of MIs during the subsequent 9 months, and a 5% incidence of ischemic strokes in a retrospective review of more than 1,600 community-dwelling U.S. patients.
The MI and ischemic stroke incidence rates in heart failure patients with reduced ejection fraction (HFrEF) were both significantly higher than in more than 4,000 patients with heart failure with preserved ejection fraction (HFpEF), Gregg C. Fonarow, MD, said while presenting a poster at the annual scientific meeting of the Heart Failure Society of America.
The findings suggest that greater attention is needed to reduce the risks for MI and stroke in HFrEF patients, suggested Dr. Fonarow, professor and cochief of cardiology at the University of California, Los Angeles, and his associates in their poster.
The study used claims data collected during July 2009-September 2016 from more than 10 million people enrolled in the United Health Group, who received care at more than 650 hospitals and about 6,600 clinics. The study included all patients diagnosed with heart failure during a hospital or emergency room visit and who had no history of a heart failure diagnosis or episode during the preceding 18 months, a left ventricular ejection fraction measurement made close to the time of the index encounter, and no stroke or MI apparent at the time of the index event. The study included 1,622 patients with HFrEF, defined as a left ventricular ejection fraction of less than 40%, 4,288 with HFpEF, defined as an ejection fraction of 50% or more, and 1,095 with heart failure with a borderline ejection fraction of 40%-49%.
The HFrEF patients had an average ejection fraction of 28%, they averaged 72 years old, 36% were women, and 8% had a prior stroke. The HFpEF patients averaged 74 years old, their average ejection fraction was 61%, 55% were women, and 11% had a prior stroke. Follow-up data on all patients were available for an average of nearly 9 months following their index heart failure event, with some patients followed as long as 1 year.
During follow-up, the incidence of ischemic stroke was 5.4% in the HFrEF patients and 3.9% in those with HFpEF, a difference that worked out to a statistically significant 40% higher ischemic stroke rate in HFrEF patients after adjustment for baseline differences between the two patient groups, Dr. Fonarow reported. The patients with a borderline ejection fraction had a 3.7% stroke incidence that fell short of a significant difference, compared with the HFrEF patient.The rate of new MIs during follow-up was 7.5% in the HFrEF patients and 3.2% in the HFpEF patients, a statistically significant 2.5-fold relatively higher MI rate with HFrEF, a statistically significant difference after adjustments. The MI incidence in patients with a borderline ejection fraction was 5.9%
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
DALLAS – Patients newly diagnosed with heart failure with reduced ejection fraction had about an 8% incidence of MIs during the subsequent 9 months, and a 5% incidence of ischemic strokes in a retrospective review of more than 1,600 community-dwelling U.S. patients.
The MI and ischemic stroke incidence rates in heart failure patients with reduced ejection fraction (HFrEF) were both significantly higher than in more than 4,000 patients with heart failure with preserved ejection fraction (HFpEF), Gregg C. Fonarow, MD, said while presenting a poster at the annual scientific meeting of the Heart Failure Society of America.
The findings suggest that greater attention is needed to reduce the risks for MI and stroke in HFrEF patients, suggested Dr. Fonarow, professor and cochief of cardiology at the University of California, Los Angeles, and his associates in their poster.
The study used claims data collected during July 2009-September 2016 from more than 10 million people enrolled in the United Health Group, who received care at more than 650 hospitals and about 6,600 clinics. The study included all patients diagnosed with heart failure during a hospital or emergency room visit and who had no history of a heart failure diagnosis or episode during the preceding 18 months, a left ventricular ejection fraction measurement made close to the time of the index encounter, and no stroke or MI apparent at the time of the index event. The study included 1,622 patients with HFrEF, defined as a left ventricular ejection fraction of less than 40%, 4,288 with HFpEF, defined as an ejection fraction of 50% or more, and 1,095 with heart failure with a borderline ejection fraction of 40%-49%.
The HFrEF patients had an average ejection fraction of 28%, they averaged 72 years old, 36% were women, and 8% had a prior stroke. The HFpEF patients averaged 74 years old, their average ejection fraction was 61%, 55% were women, and 11% had a prior stroke. Follow-up data on all patients were available for an average of nearly 9 months following their index heart failure event, with some patients followed as long as 1 year.
During follow-up, the incidence of ischemic stroke was 5.4% in the HFrEF patients and 3.9% in those with HFpEF, a difference that worked out to a statistically significant 40% higher ischemic stroke rate in HFrEF patients after adjustment for baseline differences between the two patient groups, Dr. Fonarow reported. The patients with a borderline ejection fraction had a 3.7% stroke incidence that fell short of a significant difference, compared with the HFrEF patient.The rate of new MIs during follow-up was 7.5% in the HFrEF patients and 3.2% in the HFpEF patients, a statistically significant 2.5-fold relatively higher MI rate with HFrEF, a statistically significant difference after adjustments. The MI incidence in patients with a borderline ejection fraction was 5.9%
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: HFrEF patients had a 40% higher incidence of stroke and a 2.5-fold higher incidence of MI, compared with HFpEF patients.
Data source: Retrospective review of 7,005 U.S. patients newly diagnosed with heart failure.
Disclosures: The study was funded by Janssen. Dr. Fonarow had no relevant disclosures.
VIDEO: AF ablation boosts survival in heart failure patients
BARCELONA – In patients with heart failure with reduced ejection fraction who also have atrial fibrillation, catheter ablation of the arrhythmia produced significantly improved long-term survival and a significant reduction in heart failure hospitalizations, in results from a multicenter randomized trial with more than 350 patients.
During 5-year follow-up, heart failure patients who underwent an ablative procedure for their atrial fibrillation (AF) had a statistically significant 37% lower rate of the combined primary endpoint of all-cause death or hospitalization for worsening heart failure, compared with control patients managed by standard medical therapy, Nassir F. Marrouche, MD, said at the annual congress of the European Society of Cardiology. The results also showed significant reductions from ablation, compared with controls, for the individual secondary endpoints of all-cause mortality, heart failure hospitalizations, cardiovascular mortality, and cardiovascular hospitalizations, said Dr. Marrouche, a professor of medicine and electrophysiologist at the University of Utah in Salt Lake City.
“Catheter ablation of atrial fibrillation is already done in heart failure patients, but now we have added information that this treatment may not just improve AF symptoms but also lead to a significant improvement in prognosis,” said Johannes Brachmann, MD, a coinvestigator on the study and professor and chief of cardiology at Coburg (Germany) Hospital.
The CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) trial was investigator initiated and run at 31 centers in nine countries. The study randomized patients with paroxysmal or persistent AF and heart failure with a left ventricular ejection fraction of 35% or less. All patients also had to have failed treatment with, been intolerant of, or refused treatment with at least one antiarrhythmic drug, and they had to have been implanted with either an implantable cardioverter defibrillator or a cardiac resynchronization therapy and defibrillation device. The researchers randomized 179 patients to catheter ablation by pulmonary vein isolation, and 184 patients to either a standard rate or rhythm-control regimen plus anticoagulation to prevent ischemic stroke.
The ablation procedure also cut the average AF burden by more than half, compared with medical therapy throughout the 5-year follow-up, Dr. Marrouche reported.
The results “support the need to monitor patients with heart failure for atrial fibrillation,” Dr. Brachmann said in a video interview. This means broader use of monitoring technologies to diagnose AF in heart failure patients, such as implanted loop recorders or implanted rhythm devices.
The prevalence of atrial fibrillation in patients with heart failure with reduced ejection fraction can run 30% or higher. In patients with NYHA class IV heart failure, the AF prevalence is about 50%, Dr. Brachmann said.
CASTLE AF was funded by Biotronik. Dr. Marrouche has been a consultant to and received research funding from Biotronik and from several other companies. Dr. Brachmann has been a speaker for and has received research funding from Biotronik and from Abbott and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The results of several studies have shown that patients with both atrial fibrillation and heart failure have about a 40% increased mortality, compared with heart failure patients without atrial fibrillation.
Five prior randomized controlled trials assessed the impact of AF ablation, compared with rate or rhythm control, in heart failure patients. But unlike CASTLE AF, all the prior studies used freedom from AF as the primary endpoint.
Enrolled patients were symptomatic from AF. Would asymptomatic patients get the same benefits? All enrolled patients had failed prior antiarrhythmic treatment or were intolerant or unwilling to take it. Does this mean the trial enrolled patients who generally were unresponsive to antiarrhythmic drugs, thereby skewing the results toward worse outcomes in control patients? Also, the 5-week run-in period used before randomization may have shifted enrollment toward patients well suited to ablation. The enrolled patients were also relatively young (averaging 64 years of age), and about 60% were New York Heart Association functional class II. A minority had longstanding AF. Were these younger and healthier patients better able to tolerate ablation? And can centers with less experience performing ablations have similar results?
The CASTLE AF results suggest that the time has come to offer AF ablation to patients with heart failure with reduced ejection fraction and AF, but we must be careful to select patients who are similar to the ones enrolled in this trial.
Carina Blomström-Lundqvist, MD, an electrophysiologist at Uppsala (Sweden) University Hospital, made these comments as designated discussant for the report. She has received research funding from Medtronic and Cardiome, and she has received honoraria from Biotronik, Bayer, Bristol-Myers Squibb, Medtronic, Merck, Pfizer, and Sanofi.
The results of several studies have shown that patients with both atrial fibrillation and heart failure have about a 40% increased mortality, compared with heart failure patients without atrial fibrillation.
Five prior randomized controlled trials assessed the impact of AF ablation, compared with rate or rhythm control, in heart failure patients. But unlike CASTLE AF, all the prior studies used freedom from AF as the primary endpoint.
Enrolled patients were symptomatic from AF. Would asymptomatic patients get the same benefits? All enrolled patients had failed prior antiarrhythmic treatment or were intolerant or unwilling to take it. Does this mean the trial enrolled patients who generally were unresponsive to antiarrhythmic drugs, thereby skewing the results toward worse outcomes in control patients? Also, the 5-week run-in period used before randomization may have shifted enrollment toward patients well suited to ablation. The enrolled patients were also relatively young (averaging 64 years of age), and about 60% were New York Heart Association functional class II. A minority had longstanding AF. Were these younger and healthier patients better able to tolerate ablation? And can centers with less experience performing ablations have similar results?
The CASTLE AF results suggest that the time has come to offer AF ablation to patients with heart failure with reduced ejection fraction and AF, but we must be careful to select patients who are similar to the ones enrolled in this trial.
Carina Blomström-Lundqvist, MD, an electrophysiologist at Uppsala (Sweden) University Hospital, made these comments as designated discussant for the report. She has received research funding from Medtronic and Cardiome, and she has received honoraria from Biotronik, Bayer, Bristol-Myers Squibb, Medtronic, Merck, Pfizer, and Sanofi.
The results of several studies have shown that patients with both atrial fibrillation and heart failure have about a 40% increased mortality, compared with heart failure patients without atrial fibrillation.
Five prior randomized controlled trials assessed the impact of AF ablation, compared with rate or rhythm control, in heart failure patients. But unlike CASTLE AF, all the prior studies used freedom from AF as the primary endpoint.
Enrolled patients were symptomatic from AF. Would asymptomatic patients get the same benefits? All enrolled patients had failed prior antiarrhythmic treatment or were intolerant or unwilling to take it. Does this mean the trial enrolled patients who generally were unresponsive to antiarrhythmic drugs, thereby skewing the results toward worse outcomes in control patients? Also, the 5-week run-in period used before randomization may have shifted enrollment toward patients well suited to ablation. The enrolled patients were also relatively young (averaging 64 years of age), and about 60% were New York Heart Association functional class II. A minority had longstanding AF. Were these younger and healthier patients better able to tolerate ablation? And can centers with less experience performing ablations have similar results?
The CASTLE AF results suggest that the time has come to offer AF ablation to patients with heart failure with reduced ejection fraction and AF, but we must be careful to select patients who are similar to the ones enrolled in this trial.
Carina Blomström-Lundqvist, MD, an electrophysiologist at Uppsala (Sweden) University Hospital, made these comments as designated discussant for the report. She has received research funding from Medtronic and Cardiome, and she has received honoraria from Biotronik, Bayer, Bristol-Myers Squibb, Medtronic, Merck, Pfizer, and Sanofi.
BARCELONA – In patients with heart failure with reduced ejection fraction who also have atrial fibrillation, catheter ablation of the arrhythmia produced significantly improved long-term survival and a significant reduction in heart failure hospitalizations, in results from a multicenter randomized trial with more than 350 patients.
During 5-year follow-up, heart failure patients who underwent an ablative procedure for their atrial fibrillation (AF) had a statistically significant 37% lower rate of the combined primary endpoint of all-cause death or hospitalization for worsening heart failure, compared with control patients managed by standard medical therapy, Nassir F. Marrouche, MD, said at the annual congress of the European Society of Cardiology. The results also showed significant reductions from ablation, compared with controls, for the individual secondary endpoints of all-cause mortality, heart failure hospitalizations, cardiovascular mortality, and cardiovascular hospitalizations, said Dr. Marrouche, a professor of medicine and electrophysiologist at the University of Utah in Salt Lake City.
“Catheter ablation of atrial fibrillation is already done in heart failure patients, but now we have added information that this treatment may not just improve AF symptoms but also lead to a significant improvement in prognosis,” said Johannes Brachmann, MD, a coinvestigator on the study and professor and chief of cardiology at Coburg (Germany) Hospital.
The CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) trial was investigator initiated and run at 31 centers in nine countries. The study randomized patients with paroxysmal or persistent AF and heart failure with a left ventricular ejection fraction of 35% or less. All patients also had to have failed treatment with, been intolerant of, or refused treatment with at least one antiarrhythmic drug, and they had to have been implanted with either an implantable cardioverter defibrillator or a cardiac resynchronization therapy and defibrillation device. The researchers randomized 179 patients to catheter ablation by pulmonary vein isolation, and 184 patients to either a standard rate or rhythm-control regimen plus anticoagulation to prevent ischemic stroke.
The ablation procedure also cut the average AF burden by more than half, compared with medical therapy throughout the 5-year follow-up, Dr. Marrouche reported.
The results “support the need to monitor patients with heart failure for atrial fibrillation,” Dr. Brachmann said in a video interview. This means broader use of monitoring technologies to diagnose AF in heart failure patients, such as implanted loop recorders or implanted rhythm devices.
The prevalence of atrial fibrillation in patients with heart failure with reduced ejection fraction can run 30% or higher. In patients with NYHA class IV heart failure, the AF prevalence is about 50%, Dr. Brachmann said.
CASTLE AF was funded by Biotronik. Dr. Marrouche has been a consultant to and received research funding from Biotronik and from several other companies. Dr. Brachmann has been a speaker for and has received research funding from Biotronik and from Abbott and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BARCELONA – In patients with heart failure with reduced ejection fraction who also have atrial fibrillation, catheter ablation of the arrhythmia produced significantly improved long-term survival and a significant reduction in heart failure hospitalizations, in results from a multicenter randomized trial with more than 350 patients.
During 5-year follow-up, heart failure patients who underwent an ablative procedure for their atrial fibrillation (AF) had a statistically significant 37% lower rate of the combined primary endpoint of all-cause death or hospitalization for worsening heart failure, compared with control patients managed by standard medical therapy, Nassir F. Marrouche, MD, said at the annual congress of the European Society of Cardiology. The results also showed significant reductions from ablation, compared with controls, for the individual secondary endpoints of all-cause mortality, heart failure hospitalizations, cardiovascular mortality, and cardiovascular hospitalizations, said Dr. Marrouche, a professor of medicine and electrophysiologist at the University of Utah in Salt Lake City.
“Catheter ablation of atrial fibrillation is already done in heart failure patients, but now we have added information that this treatment may not just improve AF symptoms but also lead to a significant improvement in prognosis,” said Johannes Brachmann, MD, a coinvestigator on the study and professor and chief of cardiology at Coburg (Germany) Hospital.
The CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) trial was investigator initiated and run at 31 centers in nine countries. The study randomized patients with paroxysmal or persistent AF and heart failure with a left ventricular ejection fraction of 35% or less. All patients also had to have failed treatment with, been intolerant of, or refused treatment with at least one antiarrhythmic drug, and they had to have been implanted with either an implantable cardioverter defibrillator or a cardiac resynchronization therapy and defibrillation device. The researchers randomized 179 patients to catheter ablation by pulmonary vein isolation, and 184 patients to either a standard rate or rhythm-control regimen plus anticoagulation to prevent ischemic stroke.
The ablation procedure also cut the average AF burden by more than half, compared with medical therapy throughout the 5-year follow-up, Dr. Marrouche reported.
The results “support the need to monitor patients with heart failure for atrial fibrillation,” Dr. Brachmann said in a video interview. This means broader use of monitoring technologies to diagnose AF in heart failure patients, such as implanted loop recorders or implanted rhythm devices.
The prevalence of atrial fibrillation in patients with heart failure with reduced ejection fraction can run 30% or higher. In patients with NYHA class IV heart failure, the AF prevalence is about 50%, Dr. Brachmann said.
CASTLE AF was funded by Biotronik. Dr. Marrouche has been a consultant to and received research funding from Biotronik and from several other companies. Dr. Brachmann has been a speaker for and has received research funding from Biotronik and from Abbott and Medtronic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: AF ablation was linked to a 37% 5-year reduction in mortality and heart failure hospitalization, compared with standard treatment.
Data source: CASTLE AF, a multicenter randomized trial with 363 patients.
Disclosures: CASTLE AF was funded by Biotronik. Dr. Marrouche has been a consultant to and received research funding from Biotronik and from several other companies. Dr. Brachmann has been a speaker for and has received research funding from Biotronik and from Abbott and Medtronic.