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Heart Failure Society of America (HFSA): Annual Scientific Meeting
Heart failure hospitalizations jump after major holidays
LAS VEGAS – Ah, Christmas. The lights, the good cheer, the presents under the tree. And something extra: a 14% bump in heart failure hospitalizations in the days that follow.
“Holiday heart” is a real phenomenon among patients with heart failure, Dr. Mahek Shah reported at the annual meeting of the Heart Failure Society of America.
He and his coinvestigators retrospectively analyzed the records of all 22,728 patients admitted for heart failure to Einstein Medical Center in Philadelphia in a recent 10-year period. The purpose was to learn if admission rates climbed in conjunction with national holidays, as has previously been reported for acute MI.
Sure enough, the mean daily admission rate for heart failure was 6.5 cases per day for Dec. 26-29, compared with 5.7 per day during the rest of the month. That’s a 14% jump.
Similarly, the mean daily heart failure admission rate was 11.4% greater during July 5-8 than in the rest of July, and 11% higher on the 4 days following Super Bowl Sunday than the rest of that month. Daily admissions rose by 3.3% on Jan. 2-5, compared with the rest of January, and by 2% on the 4 days following Thanksgiving, compared with the daily average for the rest of November, according to Dr. Shah of Einstein Medical Center.
Mean lengths of stay, however, weren’t significantly different for patients admitted in the 4 days post holiday than in the rest of the month, he added.
Dr. Shah offered two hypotheses for the holiday heart hospitalization phenomenon that he and his colleagues documented. One, it’s likely that many heart failure patients – just like the rest of America – overindulge in rich, salty foods at holiday celebrations that, in the case of individuals with heart failure, wreaks havoc with their extracellular fluid volume. Second, some heart failure patients probably delay in seeking medical care at holiday time because they don’t want to miss or spoil the party.
Dr. Shah reported having no financial conflicts regarding this study.
LAS VEGAS – Ah, Christmas. The lights, the good cheer, the presents under the tree. And something extra: a 14% bump in heart failure hospitalizations in the days that follow.
“Holiday heart” is a real phenomenon among patients with heart failure, Dr. Mahek Shah reported at the annual meeting of the Heart Failure Society of America.
He and his coinvestigators retrospectively analyzed the records of all 22,728 patients admitted for heart failure to Einstein Medical Center in Philadelphia in a recent 10-year period. The purpose was to learn if admission rates climbed in conjunction with national holidays, as has previously been reported for acute MI.
Sure enough, the mean daily admission rate for heart failure was 6.5 cases per day for Dec. 26-29, compared with 5.7 per day during the rest of the month. That’s a 14% jump.
Similarly, the mean daily heart failure admission rate was 11.4% greater during July 5-8 than in the rest of July, and 11% higher on the 4 days following Super Bowl Sunday than the rest of that month. Daily admissions rose by 3.3% on Jan. 2-5, compared with the rest of January, and by 2% on the 4 days following Thanksgiving, compared with the daily average for the rest of November, according to Dr. Shah of Einstein Medical Center.
Mean lengths of stay, however, weren’t significantly different for patients admitted in the 4 days post holiday than in the rest of the month, he added.
Dr. Shah offered two hypotheses for the holiday heart hospitalization phenomenon that he and his colleagues documented. One, it’s likely that many heart failure patients – just like the rest of America – overindulge in rich, salty foods at holiday celebrations that, in the case of individuals with heart failure, wreaks havoc with their extracellular fluid volume. Second, some heart failure patients probably delay in seeking medical care at holiday time because they don’t want to miss or spoil the party.
Dr. Shah reported having no financial conflicts regarding this study.
LAS VEGAS – Ah, Christmas. The lights, the good cheer, the presents under the tree. And something extra: a 14% bump in heart failure hospitalizations in the days that follow.
“Holiday heart” is a real phenomenon among patients with heart failure, Dr. Mahek Shah reported at the annual meeting of the Heart Failure Society of America.
He and his coinvestigators retrospectively analyzed the records of all 22,728 patients admitted for heart failure to Einstein Medical Center in Philadelphia in a recent 10-year period. The purpose was to learn if admission rates climbed in conjunction with national holidays, as has previously been reported for acute MI.
Sure enough, the mean daily admission rate for heart failure was 6.5 cases per day for Dec. 26-29, compared with 5.7 per day during the rest of the month. That’s a 14% jump.
Similarly, the mean daily heart failure admission rate was 11.4% greater during July 5-8 than in the rest of July, and 11% higher on the 4 days following Super Bowl Sunday than the rest of that month. Daily admissions rose by 3.3% on Jan. 2-5, compared with the rest of January, and by 2% on the 4 days following Thanksgiving, compared with the daily average for the rest of November, according to Dr. Shah of Einstein Medical Center.
Mean lengths of stay, however, weren’t significantly different for patients admitted in the 4 days post holiday than in the rest of the month, he added.
Dr. Shah offered two hypotheses for the holiday heart hospitalization phenomenon that he and his colleagues documented. One, it’s likely that many heart failure patients – just like the rest of America – overindulge in rich, salty foods at holiday celebrations that, in the case of individuals with heart failure, wreaks havoc with their extracellular fluid volume. Second, some heart failure patients probably delay in seeking medical care at holiday time because they don’t want to miss or spoil the party.
Dr. Shah reported having no financial conflicts regarding this study.
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point: Expect a noticeable spike in hospitalizations for heart failure in the 4 days following major national holidays such as Christmas, the Fourth of July, or the Super Bowl.
Major finding: Daily hospitalization rates for heart failure climb by 14% during the 4 days after Christmas and by 11% following Super Bowl Sunday and on July 5-8, compared with the daily rates or the rest of those months.
Data source: Review of daily admission rates for nearly 23,000 patients hospitalized for heart failure during a decade-long period at a large medical center.
Disclosures: Dr. Shah reported having no financial conflicts regarding this study.
Heart failure readmission cuts may be a phone call away
LAS VEGAS – A structured follow-up telephone call to heart failure patients made within 48 hours post discharge can reduce 30-day readmissions by fully one-half to two-thirds.
That’s been the experience at Stanford (Calif.) University Medical Center, where the 30-day heart failure readmission rate dropped from 20% in 524 patients at baseline to 10% among 341 patients discharged since the follow-up phone call practice was introduced, clinical nurse specialist Christine Thompson reported at the annual meeting of the Heart Failure Society of America.
The telephone call follows a scripted template embedded in the patient’s electronic health record. The template incorporates “smart text” questions that assist in identifying gaps in patient care. For example, when Ms. Thompson or another caller asks, “How have you been feeling since discharge?” it provides an opportunity to review the typical symptoms of heart failure and make sure the patient knows how to recognize them.
Other questions review medications and address the patient’s activity level, adherence to the recommended low-sodium diet, and self-weighing at home with tracking of the results. The interviewer also makes sure the patient knows his or her physician’s name, phone number, the date of the next scheduled appointment, and understands the circumstances when it’s important to call the doctor because the clinical picture is beginning to deteriorate, explained Ms. Thompson, who works in the Stanford heart failure program.
The structured telephone follow-up call was merely one element of a whole set of interventions developed by a multidisciplinary Stanford team in an effort to reduce heart failure readmissions. Other interventions included medication reconciliation, routinely scheduling an early postdischarge clinic visit, and an increased emphasis upon patient education using patient “teach back” techniques to promote mastery of key information.
In the first 14 months since the full readmission-reduction program was launched, 96% of patients reached via a postdischarge phone call demonstrated that they understood their discharge medications and how to take them.
It was possible to determine the specific contribution that the early postdischarge phone call made to the observed sharp decrease in 30-day readmissions because 61 patients didn’t get the follow-up phone call but did receive the other interventions. Their 30-day readmission rate was 28%, compared with 10% in those who did get the phone call, which translates to a 66% relative risk reduction. In a multivariate logistic regression analysis adjusted for the other interventions as well as patient age, sex, marital status, length of stay, and discharge destination, the early postdischarge follow-up phone call was independently associated with a 72% reduction in the risk of readmission within 30 days, according to Ms. Thompson.
She reported having no financial conflicts regarding this study.
LAS VEGAS – A structured follow-up telephone call to heart failure patients made within 48 hours post discharge can reduce 30-day readmissions by fully one-half to two-thirds.
That’s been the experience at Stanford (Calif.) University Medical Center, where the 30-day heart failure readmission rate dropped from 20% in 524 patients at baseline to 10% among 341 patients discharged since the follow-up phone call practice was introduced, clinical nurse specialist Christine Thompson reported at the annual meeting of the Heart Failure Society of America.
The telephone call follows a scripted template embedded in the patient’s electronic health record. The template incorporates “smart text” questions that assist in identifying gaps in patient care. For example, when Ms. Thompson or another caller asks, “How have you been feeling since discharge?” it provides an opportunity to review the typical symptoms of heart failure and make sure the patient knows how to recognize them.
Other questions review medications and address the patient’s activity level, adherence to the recommended low-sodium diet, and self-weighing at home with tracking of the results. The interviewer also makes sure the patient knows his or her physician’s name, phone number, the date of the next scheduled appointment, and understands the circumstances when it’s important to call the doctor because the clinical picture is beginning to deteriorate, explained Ms. Thompson, who works in the Stanford heart failure program.
The structured telephone follow-up call was merely one element of a whole set of interventions developed by a multidisciplinary Stanford team in an effort to reduce heart failure readmissions. Other interventions included medication reconciliation, routinely scheduling an early postdischarge clinic visit, and an increased emphasis upon patient education using patient “teach back” techniques to promote mastery of key information.
In the first 14 months since the full readmission-reduction program was launched, 96% of patients reached via a postdischarge phone call demonstrated that they understood their discharge medications and how to take them.
It was possible to determine the specific contribution that the early postdischarge phone call made to the observed sharp decrease in 30-day readmissions because 61 patients didn’t get the follow-up phone call but did receive the other interventions. Their 30-day readmission rate was 28%, compared with 10% in those who did get the phone call, which translates to a 66% relative risk reduction. In a multivariate logistic regression analysis adjusted for the other interventions as well as patient age, sex, marital status, length of stay, and discharge destination, the early postdischarge follow-up phone call was independently associated with a 72% reduction in the risk of readmission within 30 days, according to Ms. Thompson.
She reported having no financial conflicts regarding this study.
LAS VEGAS – A structured follow-up telephone call to heart failure patients made within 48 hours post discharge can reduce 30-day readmissions by fully one-half to two-thirds.
That’s been the experience at Stanford (Calif.) University Medical Center, where the 30-day heart failure readmission rate dropped from 20% in 524 patients at baseline to 10% among 341 patients discharged since the follow-up phone call practice was introduced, clinical nurse specialist Christine Thompson reported at the annual meeting of the Heart Failure Society of America.
The telephone call follows a scripted template embedded in the patient’s electronic health record. The template incorporates “smart text” questions that assist in identifying gaps in patient care. For example, when Ms. Thompson or another caller asks, “How have you been feeling since discharge?” it provides an opportunity to review the typical symptoms of heart failure and make sure the patient knows how to recognize them.
Other questions review medications and address the patient’s activity level, adherence to the recommended low-sodium diet, and self-weighing at home with tracking of the results. The interviewer also makes sure the patient knows his or her physician’s name, phone number, the date of the next scheduled appointment, and understands the circumstances when it’s important to call the doctor because the clinical picture is beginning to deteriorate, explained Ms. Thompson, who works in the Stanford heart failure program.
The structured telephone follow-up call was merely one element of a whole set of interventions developed by a multidisciplinary Stanford team in an effort to reduce heart failure readmissions. Other interventions included medication reconciliation, routinely scheduling an early postdischarge clinic visit, and an increased emphasis upon patient education using patient “teach back” techniques to promote mastery of key information.
In the first 14 months since the full readmission-reduction program was launched, 96% of patients reached via a postdischarge phone call demonstrated that they understood their discharge medications and how to take them.
It was possible to determine the specific contribution that the early postdischarge phone call made to the observed sharp decrease in 30-day readmissions because 61 patients didn’t get the follow-up phone call but did receive the other interventions. Their 30-day readmission rate was 28%, compared with 10% in those who did get the phone call, which translates to a 66% relative risk reduction. In a multivariate logistic regression analysis adjusted for the other interventions as well as patient age, sex, marital status, length of stay, and discharge destination, the early postdischarge follow-up phone call was independently associated with a 72% reduction in the risk of readmission within 30 days, according to Ms. Thompson.
She reported having no financial conflicts regarding this study.
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point: A phone call within 48 hours of discharge cut 30-day readmission rates for heart failure.
Major finding: The follow-up phone call was independently associated with a 72% reduction in risk.
Data source: This was a retrospective single-center analysis of prospectively collected data on heart failure readmissions before and after introduction of a scripted telephone follow-up call.
Disclosures: The presenter reported having no financial conflicts regarding this study.
CardioMEMS Heralds New Proactive Era in Heart Failure Management
LAS VEGAS – Clinical roll-out of a recently approved first-in-class implantable pulmonary artery measurement device ushers in a true breakthrough in the management of heart failure patients, experts forecast at the annual meeting of the Heart Failure Society of America.
Noting that in the pivotal phase III CHAMPION trial the use of the wireless implantable CardioMEMS system reduced heart failure–related admissions by 37% with a number needed to treat of just four patients for 1 year in order to avoid one hospitalization, Dr. Phillip B. Adamson declared, “It shifts us from a strategy of crisis management to one of stability management.”
Earlier this year, the Food and Drug Administration approved the implantable pulmonary artery measurement system for use in patients with New York Heart Association class III heart failure and a heart failure–related hospitalization within the previous 12 months, which defined the study population in the 550-patient randomized, single-blind, pivotal CHAMPION trial. The study included patients with heart failure with preserved ejection fraction (HFpEF) as well as those with reduced ejection fraction (HFrEF). Notably, the intervention was at least as effective in HFpEF as HFrEF.
“We saw roughly a 50% reduction in heart failure hospitalizations with a number needed to treat of two in order to prevent one hospitalization in patients with HFpEF. That’s a pretty profound result in a population of patients for which there’s been no strategy to keep them well and out of hospital,” observed Dr. Adamson, medical director of the Heart Failure Institute at Oklahoma Heart Hospital, Oklahoma City.
The 6-month results of CHAMPION have been published (Lancet 2011;377:658-66). At the heart failure meeting, Dr. Adamson and Dr. William T. Abraham presented updated results of the extended longitudinal analysis of CHAMPION. While heart failure hospitalizations were reduced by 28% during the first 6 months of the study in patients with the device turned on as compared to controls with the device off, the magnitude of benefit grew over time such that for months 6-18 in the randomized phase of the study, the relative risk reduction increased to 45%.
“It looks like we all got better over time at using this pulmonary artery pressure information,” observed Dr. Abraham, professor of internal medicine and physiology and cell biology and director of the division of cardiovascular medicine at Ohio State University, Columbus.
He drew particular attention to the highly significant 16% reduction in the risk of the combined secondary endpoint of death or all-cause hospitalization with the device on over the full duration of the randomized study; that’s an outcome many current standard-of-care pharmacologic and device therapies haven’t been able to achieve.
When former control subjects were crossed over to device-on for 13 months of open-label management, their annualized rate of heart failure hospitalizations dropped by 48%, he continued.
The principle behind this management strategy is that measurable changes in pulmonary artery pressures occur at least several weeks before patients experience symptomatic deterioration and weight gain. And these pressure changes are actionable. By remotely monitoring hemodynamic pressures via the implanted device and promptly adjusting medications in order bring elevated pressures back into target range – for example, to a mean arterial pressure of 10-25 mm Hg – heart failure hospitalizations are avoided.
“In CHAMPION, even if the patient looked good and felt good, if the pressures were elevated the protocol required that they be lowered to target ranges,” Dr. Abraham explained.
The system works like this: On a daily basis, a patient lies down on a special pillow that interrogates the device for 18 seconds, then transmits the pressure readings to an Internet website. If the readings fall outside target range, an e-mail notification is automatically sent to the patient’s health care provider. Once the office receives the message then a nurse, nurse practitioner, or physician assistant phones the patient and adjusts medications according to a defined protocol based on scripted questions.
On the other hand, if the patient’s pressures are stable, once-weekly review of the readings is generally sufficient. That was the protocol in CHAMPION.
“Patients don’t decompensate overnight,” Dr. Abraham observed. “They decompensate over many days to weeks.”
Audience members had lots of questions about billing. Dr. Adamson explained that remote pulmonary artery pressure monitoring is billable every 31 days, although a physician can’t bill for both pulmonary artery pressure and impedance monitoring.
“You have to have a documented encounter in the patient’s chart in which you reviewed the pressures and what your decision-making process was: either the patient was contacted and the medications increased, or you decided not to change the medications,” he said.
Also, as of October, Medicare covers the device implantation procedure under a new-technology add-on. Large private insurers are expected to follow suit. A reimbursable procedure is something of a rarity for heart failure specialists, although surgeons and general cardiologists can readily perform the implantation as well, according to Dr. Adamson.
Although for now the device is indicated in patients with NYHA class III heart failure, consideration is now being given to a possible extension of the indication to patients with class II disease as well. That’s largely because of an analysis of Medicare data led by Dr. Adamson that showed that nationally, patients with class II or III heart failure averaged a 24.7% 30-day hospital readmission rate as compared to an 18.5% rate among Medicare participants in CHAMPION.
Asked about patient acceptance of the monitoring program, Dr. Abraham said it was excellent in CHAMPION.
“In the trial, we asked patients to take a measurement daily, and on average, we got measurements on 6 out of 7 days,” he noted.
That high adherence rate came as no surprise to Sara Paul, a registered nurse who serves as director of the heart function clinic at Catawba Valley Medical Center in Conover, N.C.
“I think when patients find something that makes them feel better, they’re going to do it. I’m actually a little more concerned about the opposite: the patient who decides to freely partake of salty, fatty foods like pizza and hot dogs, because they know you’re going to be watching them and taking care of them. That’s my concern,” she said.
Under the medication adjustment protocols used in CHAMPION, the initial presumption was that elevated pressures were due to volume overload, so the first step was a simple increase in diuretic therapy. Many patients responded to that, according to Dr. Abraham. If not, the second-line maneuver was to add or increase a nitrate vasodilator on the presumption that the elevated pressures were most likely related to a change in venous capacitance.
Ms. Paul stressed one major caveat regarding pulmonary artery pressure–guided therapy via remote hemodynamic monitoring: The device itself is not directly therapeutic.
“This is not a device that administers treatment. So if you’re going to put this device in a patient, you’d better use the information,” she said.
Dr. Adamson and Dr. Abraham reported receiving speakers honoraria from St. Jude Medical, which markets the CardioMEMS system, as well as serving as consultants to numerous other health care companies. Ms. Paul reported having no financial conflicts.
LAS VEGAS – Clinical roll-out of a recently approved first-in-class implantable pulmonary artery measurement device ushers in a true breakthrough in the management of heart failure patients, experts forecast at the annual meeting of the Heart Failure Society of America.
Noting that in the pivotal phase III CHAMPION trial the use of the wireless implantable CardioMEMS system reduced heart failure–related admissions by 37% with a number needed to treat of just four patients for 1 year in order to avoid one hospitalization, Dr. Phillip B. Adamson declared, “It shifts us from a strategy of crisis management to one of stability management.”
Earlier this year, the Food and Drug Administration approved the implantable pulmonary artery measurement system for use in patients with New York Heart Association class III heart failure and a heart failure–related hospitalization within the previous 12 months, which defined the study population in the 550-patient randomized, single-blind, pivotal CHAMPION trial. The study included patients with heart failure with preserved ejection fraction (HFpEF) as well as those with reduced ejection fraction (HFrEF). Notably, the intervention was at least as effective in HFpEF as HFrEF.
“We saw roughly a 50% reduction in heart failure hospitalizations with a number needed to treat of two in order to prevent one hospitalization in patients with HFpEF. That’s a pretty profound result in a population of patients for which there’s been no strategy to keep them well and out of hospital,” observed Dr. Adamson, medical director of the Heart Failure Institute at Oklahoma Heart Hospital, Oklahoma City.
The 6-month results of CHAMPION have been published (Lancet 2011;377:658-66). At the heart failure meeting, Dr. Adamson and Dr. William T. Abraham presented updated results of the extended longitudinal analysis of CHAMPION. While heart failure hospitalizations were reduced by 28% during the first 6 months of the study in patients with the device turned on as compared to controls with the device off, the magnitude of benefit grew over time such that for months 6-18 in the randomized phase of the study, the relative risk reduction increased to 45%.
“It looks like we all got better over time at using this pulmonary artery pressure information,” observed Dr. Abraham, professor of internal medicine and physiology and cell biology and director of the division of cardiovascular medicine at Ohio State University, Columbus.
He drew particular attention to the highly significant 16% reduction in the risk of the combined secondary endpoint of death or all-cause hospitalization with the device on over the full duration of the randomized study; that’s an outcome many current standard-of-care pharmacologic and device therapies haven’t been able to achieve.
When former control subjects were crossed over to device-on for 13 months of open-label management, their annualized rate of heart failure hospitalizations dropped by 48%, he continued.
The principle behind this management strategy is that measurable changes in pulmonary artery pressures occur at least several weeks before patients experience symptomatic deterioration and weight gain. And these pressure changes are actionable. By remotely monitoring hemodynamic pressures via the implanted device and promptly adjusting medications in order bring elevated pressures back into target range – for example, to a mean arterial pressure of 10-25 mm Hg – heart failure hospitalizations are avoided.
“In CHAMPION, even if the patient looked good and felt good, if the pressures were elevated the protocol required that they be lowered to target ranges,” Dr. Abraham explained.
The system works like this: On a daily basis, a patient lies down on a special pillow that interrogates the device for 18 seconds, then transmits the pressure readings to an Internet website. If the readings fall outside target range, an e-mail notification is automatically sent to the patient’s health care provider. Once the office receives the message then a nurse, nurse practitioner, or physician assistant phones the patient and adjusts medications according to a defined protocol based on scripted questions.
On the other hand, if the patient’s pressures are stable, once-weekly review of the readings is generally sufficient. That was the protocol in CHAMPION.
“Patients don’t decompensate overnight,” Dr. Abraham observed. “They decompensate over many days to weeks.”
Audience members had lots of questions about billing. Dr. Adamson explained that remote pulmonary artery pressure monitoring is billable every 31 days, although a physician can’t bill for both pulmonary artery pressure and impedance monitoring.
“You have to have a documented encounter in the patient’s chart in which you reviewed the pressures and what your decision-making process was: either the patient was contacted and the medications increased, or you decided not to change the medications,” he said.
Also, as of October, Medicare covers the device implantation procedure under a new-technology add-on. Large private insurers are expected to follow suit. A reimbursable procedure is something of a rarity for heart failure specialists, although surgeons and general cardiologists can readily perform the implantation as well, according to Dr. Adamson.
Although for now the device is indicated in patients with NYHA class III heart failure, consideration is now being given to a possible extension of the indication to patients with class II disease as well. That’s largely because of an analysis of Medicare data led by Dr. Adamson that showed that nationally, patients with class II or III heart failure averaged a 24.7% 30-day hospital readmission rate as compared to an 18.5% rate among Medicare participants in CHAMPION.
Asked about patient acceptance of the monitoring program, Dr. Abraham said it was excellent in CHAMPION.
“In the trial, we asked patients to take a measurement daily, and on average, we got measurements on 6 out of 7 days,” he noted.
That high adherence rate came as no surprise to Sara Paul, a registered nurse who serves as director of the heart function clinic at Catawba Valley Medical Center in Conover, N.C.
“I think when patients find something that makes them feel better, they’re going to do it. I’m actually a little more concerned about the opposite: the patient who decides to freely partake of salty, fatty foods like pizza and hot dogs, because they know you’re going to be watching them and taking care of them. That’s my concern,” she said.
Under the medication adjustment protocols used in CHAMPION, the initial presumption was that elevated pressures were due to volume overload, so the first step was a simple increase in diuretic therapy. Many patients responded to that, according to Dr. Abraham. If not, the second-line maneuver was to add or increase a nitrate vasodilator on the presumption that the elevated pressures were most likely related to a change in venous capacitance.
Ms. Paul stressed one major caveat regarding pulmonary artery pressure–guided therapy via remote hemodynamic monitoring: The device itself is not directly therapeutic.
“This is not a device that administers treatment. So if you’re going to put this device in a patient, you’d better use the information,” she said.
Dr. Adamson and Dr. Abraham reported receiving speakers honoraria from St. Jude Medical, which markets the CardioMEMS system, as well as serving as consultants to numerous other health care companies. Ms. Paul reported having no financial conflicts.
LAS VEGAS – Clinical roll-out of a recently approved first-in-class implantable pulmonary artery measurement device ushers in a true breakthrough in the management of heart failure patients, experts forecast at the annual meeting of the Heart Failure Society of America.
Noting that in the pivotal phase III CHAMPION trial the use of the wireless implantable CardioMEMS system reduced heart failure–related admissions by 37% with a number needed to treat of just four patients for 1 year in order to avoid one hospitalization, Dr. Phillip B. Adamson declared, “It shifts us from a strategy of crisis management to one of stability management.”
Earlier this year, the Food and Drug Administration approved the implantable pulmonary artery measurement system for use in patients with New York Heart Association class III heart failure and a heart failure–related hospitalization within the previous 12 months, which defined the study population in the 550-patient randomized, single-blind, pivotal CHAMPION trial. The study included patients with heart failure with preserved ejection fraction (HFpEF) as well as those with reduced ejection fraction (HFrEF). Notably, the intervention was at least as effective in HFpEF as HFrEF.
“We saw roughly a 50% reduction in heart failure hospitalizations with a number needed to treat of two in order to prevent one hospitalization in patients with HFpEF. That’s a pretty profound result in a population of patients for which there’s been no strategy to keep them well and out of hospital,” observed Dr. Adamson, medical director of the Heart Failure Institute at Oklahoma Heart Hospital, Oklahoma City.
The 6-month results of CHAMPION have been published (Lancet 2011;377:658-66). At the heart failure meeting, Dr. Adamson and Dr. William T. Abraham presented updated results of the extended longitudinal analysis of CHAMPION. While heart failure hospitalizations were reduced by 28% during the first 6 months of the study in patients with the device turned on as compared to controls with the device off, the magnitude of benefit grew over time such that for months 6-18 in the randomized phase of the study, the relative risk reduction increased to 45%.
“It looks like we all got better over time at using this pulmonary artery pressure information,” observed Dr. Abraham, professor of internal medicine and physiology and cell biology and director of the division of cardiovascular medicine at Ohio State University, Columbus.
He drew particular attention to the highly significant 16% reduction in the risk of the combined secondary endpoint of death or all-cause hospitalization with the device on over the full duration of the randomized study; that’s an outcome many current standard-of-care pharmacologic and device therapies haven’t been able to achieve.
When former control subjects were crossed over to device-on for 13 months of open-label management, their annualized rate of heart failure hospitalizations dropped by 48%, he continued.
The principle behind this management strategy is that measurable changes in pulmonary artery pressures occur at least several weeks before patients experience symptomatic deterioration and weight gain. And these pressure changes are actionable. By remotely monitoring hemodynamic pressures via the implanted device and promptly adjusting medications in order bring elevated pressures back into target range – for example, to a mean arterial pressure of 10-25 mm Hg – heart failure hospitalizations are avoided.
“In CHAMPION, even if the patient looked good and felt good, if the pressures were elevated the protocol required that they be lowered to target ranges,” Dr. Abraham explained.
The system works like this: On a daily basis, a patient lies down on a special pillow that interrogates the device for 18 seconds, then transmits the pressure readings to an Internet website. If the readings fall outside target range, an e-mail notification is automatically sent to the patient’s health care provider. Once the office receives the message then a nurse, nurse practitioner, or physician assistant phones the patient and adjusts medications according to a defined protocol based on scripted questions.
On the other hand, if the patient’s pressures are stable, once-weekly review of the readings is generally sufficient. That was the protocol in CHAMPION.
“Patients don’t decompensate overnight,” Dr. Abraham observed. “They decompensate over many days to weeks.”
Audience members had lots of questions about billing. Dr. Adamson explained that remote pulmonary artery pressure monitoring is billable every 31 days, although a physician can’t bill for both pulmonary artery pressure and impedance monitoring.
“You have to have a documented encounter in the patient’s chart in which you reviewed the pressures and what your decision-making process was: either the patient was contacted and the medications increased, or you decided not to change the medications,” he said.
Also, as of October, Medicare covers the device implantation procedure under a new-technology add-on. Large private insurers are expected to follow suit. A reimbursable procedure is something of a rarity for heart failure specialists, although surgeons and general cardiologists can readily perform the implantation as well, according to Dr. Adamson.
Although for now the device is indicated in patients with NYHA class III heart failure, consideration is now being given to a possible extension of the indication to patients with class II disease as well. That’s largely because of an analysis of Medicare data led by Dr. Adamson that showed that nationally, patients with class II or III heart failure averaged a 24.7% 30-day hospital readmission rate as compared to an 18.5% rate among Medicare participants in CHAMPION.
Asked about patient acceptance of the monitoring program, Dr. Abraham said it was excellent in CHAMPION.
“In the trial, we asked patients to take a measurement daily, and on average, we got measurements on 6 out of 7 days,” he noted.
That high adherence rate came as no surprise to Sara Paul, a registered nurse who serves as director of the heart function clinic at Catawba Valley Medical Center in Conover, N.C.
“I think when patients find something that makes them feel better, they’re going to do it. I’m actually a little more concerned about the opposite: the patient who decides to freely partake of salty, fatty foods like pizza and hot dogs, because they know you’re going to be watching them and taking care of them. That’s my concern,” she said.
Under the medication adjustment protocols used in CHAMPION, the initial presumption was that elevated pressures were due to volume overload, so the first step was a simple increase in diuretic therapy. Many patients responded to that, according to Dr. Abraham. If not, the second-line maneuver was to add or increase a nitrate vasodilator on the presumption that the elevated pressures were most likely related to a change in venous capacitance.
Ms. Paul stressed one major caveat regarding pulmonary artery pressure–guided therapy via remote hemodynamic monitoring: The device itself is not directly therapeutic.
“This is not a device that administers treatment. So if you’re going to put this device in a patient, you’d better use the information,” she said.
Dr. Adamson and Dr. Abraham reported receiving speakers honoraria from St. Jude Medical, which markets the CardioMEMS system, as well as serving as consultants to numerous other health care companies. Ms. Paul reported having no financial conflicts.
EXPERT ANALYSIS FROM THE HFSA ANNUAL SCIENTIFIC MEETING
CardioMEMS heralds new proactive era in heart failure management
LAS VEGAS – Clinical roll-out of a recently approved first-in-class implantable pulmonary artery measurement device ushers in a true breakthrough in the management of heart failure patients, experts forecast at the annual meeting of the Heart Failure Society of America.
Noting that in the pivotal phase III CHAMPION trial the use of the wireless implantable CardioMEMS system reduced heart failure–related admissions by 37% with a number needed to treat of just four patients for 1 year in order to avoid one hospitalization, Dr. Phillip B. Adamson declared, “It shifts us from a strategy of crisis management to one of stability management.”
Earlier this year, the Food and Drug Administration approved the implantable pulmonary artery measurement system for use in patients with New York Heart Association class III heart failure and a heart failure–related hospitalization within the previous 12 months, which defined the study population in the 550-patient randomized, single-blind, pivotal CHAMPION trial. The study included patients with heart failure with preserved ejection fraction (HFpEF) as well as those with reduced ejection fraction (HFrEF). Notably, the intervention was at least as effective in HFpEF as HFrEF.
“We saw roughly a 50% reduction in heart failure hospitalizations with a number needed to treat of two in order to prevent one hospitalization in patients with HFpEF. That’s a pretty profound result in a population of patients for which there’s been no strategy to keep them well and out of hospital,” observed Dr. Adamson, medical director of the Heart Failure Institute at Oklahoma Heart Hospital, Oklahoma City.
The 6-month results of CHAMPION have been published (Lancet 2011;377:658-66). At the heart failure meeting, Dr. Adamson and Dr. William T. Abraham presented updated results of the extended longitudinal analysis of CHAMPION. While heart failure hospitalizations were reduced by 28% during the first 6 months of the study in patients with the device turned on as compared to controls with the device off, the magnitude of benefit grew over time such that for months 6-18 in the randomized phase of the study, the relative risk reduction increased to 45%.
“It looks like we all got better over time at using this pulmonary artery pressure information,” observed Dr. Abraham, professor of internal medicine and physiology and cell biology and director of the division of cardiovascular medicine at Ohio State University, Columbus.
He drew particular attention to the highly significant 16% reduction in the risk of the combined secondary endpoint of death or all-cause hospitalization with the device on over the full duration of the randomized study; that’s an outcome many current standard-of-care pharmacologic and device therapies haven’t been able to achieve.
When former control subjects were crossed over to device-on for 13 months of open-label management, their annualized rate of heart failure hospitalizations dropped by 48%, he continued.
The principle behind this management strategy is that measurable changes in pulmonary artery pressures occur at least several weeks before patients experience symptomatic deterioration and weight gain. And these pressure changes are actionable. By remotely monitoring hemodynamic pressures via the implanted device and promptly adjusting medications in order bring elevated pressures back into target range – for example, to a mean arterial pressure of 10-25 mm Hg – heart failure hospitalizations are avoided.
“In CHAMPION, even if the patient looked good and felt good, if the pressures were elevated the protocol required that they be lowered to target ranges,” Dr. Abraham explained.
The system works like this: On a daily basis, a patient lies down on a special pillow that interrogates the device for 18 seconds, then transmits the pressure readings to an Internet website. If the readings fall outside target range, an e-mail notification is automatically sent to the patient’s health care provider. Once the office receives the message then a nurse, nurse practitioner, or physician assistant phones the patient and adjusts medications according to a defined protocol based on scripted questions.
On the other hand, if the patient’s pressures are stable, once-weekly review of the readings is generally sufficient. That was the protocol in CHAMPION.
“Patients don’t decompensate overnight,” Dr. Abraham observed. “They decompensate over many days to weeks.”
Audience members had lots of questions about billing. Dr. Adamson explained that remote pulmonary artery pressure monitoring is billable every 31 days, although a physician can’t bill for both pulmonary artery pressure and impedance monitoring.
“You have to have a documented encounter in the patient’s chart in which you reviewed the pressures and what your decision-making process was: either the patient was contacted and the medications increased, or you decided not to change the medications,” he said.
Also, as of October, Medicare covers the device implantation procedure under a new-technology add-on. Large private insurers are expected to follow suit. A reimbursable procedure is something of a rarity for heart failure specialists, although surgeons and general cardiologists can readily perform the implantation as well, according to Dr. Adamson.
Although for now the device is indicated in patients with NYHA class III heart failure, consideration is now being given to a possible extension of the indication to patients with class II disease as well. That’s largely because of an analysis of Medicare data led by Dr. Adamson that showed that nationally, patients with class II or III heart failure averaged a 24.7% 30-day hospital readmission rate as compared to an 18.5% rate among Medicare participants in CHAMPION.
Asked about patient acceptance of the monitoring program, Dr. Abraham said it was excellent in CHAMPION.
“In the trial, we asked patients to take a measurement daily, and on average, we got measurements on 6 out of 7 days,” he noted.
That high adherence rate came as no surprise to Sara Paul, a registered nurse who serves as director of the heart function clinic at Catawba Valley Medical Center in Conover, N.C.
“I think when patients find something that makes them feel better, they’re going to do it. I’m actually a little more concerned about the opposite: the patient who decides to freely partake of salty, fatty foods like pizza and hot dogs, because they know you’re going to be watching them and taking care of them. That’s my concern,” she said.
Under the medication adjustment protocols used in CHAMPION, the initial presumption was that elevated pressures were due to volume overload, so the first step was a simple increase in diuretic therapy. Many patients responded to that, according to Dr. Abraham. If not, the second-line maneuver was to add or increase a nitrate vasodilator on the presumption that the elevated pressures were most likely related to a change in venous capacitance.
Ms. Paul stressed one major caveat regarding pulmonary artery pressure–guided therapy via remote hemodynamic monitoring: The device itself is not directly therapeutic.
“This is not a device that administers treatment. So if you’re going to put this device in a patient, you’d better use the information,” she said.
Dr. Adamson and Dr. Abraham reported receiving speakers honoraria from St. Jude Medical, which markets the CardioMEMS system, as well as serving as consultants to numerous other health care companies. Ms. Paul reported having no financial conflicts.
LAS VEGAS – Clinical roll-out of a recently approved first-in-class implantable pulmonary artery measurement device ushers in a true breakthrough in the management of heart failure patients, experts forecast at the annual meeting of the Heart Failure Society of America.
Noting that in the pivotal phase III CHAMPION trial the use of the wireless implantable CardioMEMS system reduced heart failure–related admissions by 37% with a number needed to treat of just four patients for 1 year in order to avoid one hospitalization, Dr. Phillip B. Adamson declared, “It shifts us from a strategy of crisis management to one of stability management.”
Earlier this year, the Food and Drug Administration approved the implantable pulmonary artery measurement system for use in patients with New York Heart Association class III heart failure and a heart failure–related hospitalization within the previous 12 months, which defined the study population in the 550-patient randomized, single-blind, pivotal CHAMPION trial. The study included patients with heart failure with preserved ejection fraction (HFpEF) as well as those with reduced ejection fraction (HFrEF). Notably, the intervention was at least as effective in HFpEF as HFrEF.
“We saw roughly a 50% reduction in heart failure hospitalizations with a number needed to treat of two in order to prevent one hospitalization in patients with HFpEF. That’s a pretty profound result in a population of patients for which there’s been no strategy to keep them well and out of hospital,” observed Dr. Adamson, medical director of the Heart Failure Institute at Oklahoma Heart Hospital, Oklahoma City.
The 6-month results of CHAMPION have been published (Lancet 2011;377:658-66). At the heart failure meeting, Dr. Adamson and Dr. William T. Abraham presented updated results of the extended longitudinal analysis of CHAMPION. While heart failure hospitalizations were reduced by 28% during the first 6 months of the study in patients with the device turned on as compared to controls with the device off, the magnitude of benefit grew over time such that for months 6-18 in the randomized phase of the study, the relative risk reduction increased to 45%.
“It looks like we all got better over time at using this pulmonary artery pressure information,” observed Dr. Abraham, professor of internal medicine and physiology and cell biology and director of the division of cardiovascular medicine at Ohio State University, Columbus.
He drew particular attention to the highly significant 16% reduction in the risk of the combined secondary endpoint of death or all-cause hospitalization with the device on over the full duration of the randomized study; that’s an outcome many current standard-of-care pharmacologic and device therapies haven’t been able to achieve.
When former control subjects were crossed over to device-on for 13 months of open-label management, their annualized rate of heart failure hospitalizations dropped by 48%, he continued.
The principle behind this management strategy is that measurable changes in pulmonary artery pressures occur at least several weeks before patients experience symptomatic deterioration and weight gain. And these pressure changes are actionable. By remotely monitoring hemodynamic pressures via the implanted device and promptly adjusting medications in order bring elevated pressures back into target range – for example, to a mean arterial pressure of 10-25 mm Hg – heart failure hospitalizations are avoided.
“In CHAMPION, even if the patient looked good and felt good, if the pressures were elevated the protocol required that they be lowered to target ranges,” Dr. Abraham explained.
The system works like this: On a daily basis, a patient lies down on a special pillow that interrogates the device for 18 seconds, then transmits the pressure readings to an Internet website. If the readings fall outside target range, an e-mail notification is automatically sent to the patient’s health care provider. Once the office receives the message then a nurse, nurse practitioner, or physician assistant phones the patient and adjusts medications according to a defined protocol based on scripted questions.
On the other hand, if the patient’s pressures are stable, once-weekly review of the readings is generally sufficient. That was the protocol in CHAMPION.
“Patients don’t decompensate overnight,” Dr. Abraham observed. “They decompensate over many days to weeks.”
Audience members had lots of questions about billing. Dr. Adamson explained that remote pulmonary artery pressure monitoring is billable every 31 days, although a physician can’t bill for both pulmonary artery pressure and impedance monitoring.
“You have to have a documented encounter in the patient’s chart in which you reviewed the pressures and what your decision-making process was: either the patient was contacted and the medications increased, or you decided not to change the medications,” he said.
Also, as of October, Medicare covers the device implantation procedure under a new-technology add-on. Large private insurers are expected to follow suit. A reimbursable procedure is something of a rarity for heart failure specialists, although surgeons and general cardiologists can readily perform the implantation as well, according to Dr. Adamson.
Although for now the device is indicated in patients with NYHA class III heart failure, consideration is now being given to a possible extension of the indication to patients with class II disease as well. That’s largely because of an analysis of Medicare data led by Dr. Adamson that showed that nationally, patients with class II or III heart failure averaged a 24.7% 30-day hospital readmission rate as compared to an 18.5% rate among Medicare participants in CHAMPION.
Asked about patient acceptance of the monitoring program, Dr. Abraham said it was excellent in CHAMPION.
“In the trial, we asked patients to take a measurement daily, and on average, we got measurements on 6 out of 7 days,” he noted.
That high adherence rate came as no surprise to Sara Paul, a registered nurse who serves as director of the heart function clinic at Catawba Valley Medical Center in Conover, N.C.
“I think when patients find something that makes them feel better, they’re going to do it. I’m actually a little more concerned about the opposite: the patient who decides to freely partake of salty, fatty foods like pizza and hot dogs, because they know you’re going to be watching them and taking care of them. That’s my concern,” she said.
Under the medication adjustment protocols used in CHAMPION, the initial presumption was that elevated pressures were due to volume overload, so the first step was a simple increase in diuretic therapy. Many patients responded to that, according to Dr. Abraham. If not, the second-line maneuver was to add or increase a nitrate vasodilator on the presumption that the elevated pressures were most likely related to a change in venous capacitance.
Ms. Paul stressed one major caveat regarding pulmonary artery pressure–guided therapy via remote hemodynamic monitoring: The device itself is not directly therapeutic.
“This is not a device that administers treatment. So if you’re going to put this device in a patient, you’d better use the information,” she said.
Dr. Adamson and Dr. Abraham reported receiving speakers honoraria from St. Jude Medical, which markets the CardioMEMS system, as well as serving as consultants to numerous other health care companies. Ms. Paul reported having no financial conflicts.
LAS VEGAS – Clinical roll-out of a recently approved first-in-class implantable pulmonary artery measurement device ushers in a true breakthrough in the management of heart failure patients, experts forecast at the annual meeting of the Heart Failure Society of America.
Noting that in the pivotal phase III CHAMPION trial the use of the wireless implantable CardioMEMS system reduced heart failure–related admissions by 37% with a number needed to treat of just four patients for 1 year in order to avoid one hospitalization, Dr. Phillip B. Adamson declared, “It shifts us from a strategy of crisis management to one of stability management.”
Earlier this year, the Food and Drug Administration approved the implantable pulmonary artery measurement system for use in patients with New York Heart Association class III heart failure and a heart failure–related hospitalization within the previous 12 months, which defined the study population in the 550-patient randomized, single-blind, pivotal CHAMPION trial. The study included patients with heart failure with preserved ejection fraction (HFpEF) as well as those with reduced ejection fraction (HFrEF). Notably, the intervention was at least as effective in HFpEF as HFrEF.
“We saw roughly a 50% reduction in heart failure hospitalizations with a number needed to treat of two in order to prevent one hospitalization in patients with HFpEF. That’s a pretty profound result in a population of patients for which there’s been no strategy to keep them well and out of hospital,” observed Dr. Adamson, medical director of the Heart Failure Institute at Oklahoma Heart Hospital, Oklahoma City.
The 6-month results of CHAMPION have been published (Lancet 2011;377:658-66). At the heart failure meeting, Dr. Adamson and Dr. William T. Abraham presented updated results of the extended longitudinal analysis of CHAMPION. While heart failure hospitalizations were reduced by 28% during the first 6 months of the study in patients with the device turned on as compared to controls with the device off, the magnitude of benefit grew over time such that for months 6-18 in the randomized phase of the study, the relative risk reduction increased to 45%.
“It looks like we all got better over time at using this pulmonary artery pressure information,” observed Dr. Abraham, professor of internal medicine and physiology and cell biology and director of the division of cardiovascular medicine at Ohio State University, Columbus.
He drew particular attention to the highly significant 16% reduction in the risk of the combined secondary endpoint of death or all-cause hospitalization with the device on over the full duration of the randomized study; that’s an outcome many current standard-of-care pharmacologic and device therapies haven’t been able to achieve.
When former control subjects were crossed over to device-on for 13 months of open-label management, their annualized rate of heart failure hospitalizations dropped by 48%, he continued.
The principle behind this management strategy is that measurable changes in pulmonary artery pressures occur at least several weeks before patients experience symptomatic deterioration and weight gain. And these pressure changes are actionable. By remotely monitoring hemodynamic pressures via the implanted device and promptly adjusting medications in order bring elevated pressures back into target range – for example, to a mean arterial pressure of 10-25 mm Hg – heart failure hospitalizations are avoided.
“In CHAMPION, even if the patient looked good and felt good, if the pressures were elevated the protocol required that they be lowered to target ranges,” Dr. Abraham explained.
The system works like this: On a daily basis, a patient lies down on a special pillow that interrogates the device for 18 seconds, then transmits the pressure readings to an Internet website. If the readings fall outside target range, an e-mail notification is automatically sent to the patient’s health care provider. Once the office receives the message then a nurse, nurse practitioner, or physician assistant phones the patient and adjusts medications according to a defined protocol based on scripted questions.
On the other hand, if the patient’s pressures are stable, once-weekly review of the readings is generally sufficient. That was the protocol in CHAMPION.
“Patients don’t decompensate overnight,” Dr. Abraham observed. “They decompensate over many days to weeks.”
Audience members had lots of questions about billing. Dr. Adamson explained that remote pulmonary artery pressure monitoring is billable every 31 days, although a physician can’t bill for both pulmonary artery pressure and impedance monitoring.
“You have to have a documented encounter in the patient’s chart in which you reviewed the pressures and what your decision-making process was: either the patient was contacted and the medications increased, or you decided not to change the medications,” he said.
Also, as of October, Medicare covers the device implantation procedure under a new-technology add-on. Large private insurers are expected to follow suit. A reimbursable procedure is something of a rarity for heart failure specialists, although surgeons and general cardiologists can readily perform the implantation as well, according to Dr. Adamson.
Although for now the device is indicated in patients with NYHA class III heart failure, consideration is now being given to a possible extension of the indication to patients with class II disease as well. That’s largely because of an analysis of Medicare data led by Dr. Adamson that showed that nationally, patients with class II or III heart failure averaged a 24.7% 30-day hospital readmission rate as compared to an 18.5% rate among Medicare participants in CHAMPION.
Asked about patient acceptance of the monitoring program, Dr. Abraham said it was excellent in CHAMPION.
“In the trial, we asked patients to take a measurement daily, and on average, we got measurements on 6 out of 7 days,” he noted.
That high adherence rate came as no surprise to Sara Paul, a registered nurse who serves as director of the heart function clinic at Catawba Valley Medical Center in Conover, N.C.
“I think when patients find something that makes them feel better, they’re going to do it. I’m actually a little more concerned about the opposite: the patient who decides to freely partake of salty, fatty foods like pizza and hot dogs, because they know you’re going to be watching them and taking care of them. That’s my concern,” she said.
Under the medication adjustment protocols used in CHAMPION, the initial presumption was that elevated pressures were due to volume overload, so the first step was a simple increase in diuretic therapy. Many patients responded to that, according to Dr. Abraham. If not, the second-line maneuver was to add or increase a nitrate vasodilator on the presumption that the elevated pressures were most likely related to a change in venous capacitance.
Ms. Paul stressed one major caveat regarding pulmonary artery pressure–guided therapy via remote hemodynamic monitoring: The device itself is not directly therapeutic.
“This is not a device that administers treatment. So if you’re going to put this device in a patient, you’d better use the information,” she said.
Dr. Adamson and Dr. Abraham reported receiving speakers honoraria from St. Jude Medical, which markets the CardioMEMS system, as well as serving as consultants to numerous other health care companies. Ms. Paul reported having no financial conflicts.
EXPERT ANALYSIS FROM THE HFSA ANNUAL SCIENTIFIC MEETING
Should LCZ696 receive a level I indication?
LAS VEGAS – Additional findings from the landmark PARADIGM-HF trial presented at the annual meeting of the Heart Failure Society of America provided what many observers deemed a persuasive case for the novel angiotensin receptor neprilysin inhibitor known for now as LCZ696 as deserving of a level I indication in the next update of the major heart failure management guidelines.
At a special session added late to the meeting program in the wake of the spectacularly positive top-line results of PARADIGM-HF presented just a few weeks earlier at the European Society of Cardiology meeting in Barcelona, an international panel of heart failure heavyweights tackled questions about the study’s implications, including whether the results need replication in a second randomized controlled trial before LCZ696 can win regulatory approval. And once approved, should guidelines committees give it a level I, must-use indication? How applicable are the PARADIGM-HF results to the broader population of heart failure patients, and in particular black patients and older individuals with class III/IV heart failure? And what about patients with heart failure with preserved ejection fraction (HFpEF) ?
In other words, does PARADIGM-HF, with more than 8,400 randomized subjects, represent a true paradigm shift in heart failure management?
For coprincipal investigator Dr. Milton Packer, the answer is a resounding yes.
“For the past 25 years, the magnitude of the effect of ACE inhibitors on cardiovascular mortality – about an 18% reduction – has created an ethical mandate for their use in all patients with chronic heart failure who could tolerate treatment with these drugs. The finding that LCZ696 has a 20% greater effect on cardiovascular mortality than ACE inhibitors strongly supports the conclusion that LCZ696 should replace the current use of ACE inhibitors and angiotensin receptor blockers in the management of chronic heart failure,” said Dr. Packer, professor and chair of the department of clinical sciences at University of Texas Southwestern Medical Center, Dallas.
His coprincipal investigator, Dr. John J.V. McMurray, cited the statistical strength of the PARADIGM-HF results for the primary composite outcome of cardiovascular death or heart failure hospitalization, which had an extraordinary P value of .0000004, in making the case that the trial findings are sufficient to win regulatory approval without a confirmatory study.
He noted that the regulatory standard in the United States and Europe is that a positive clinical trial having a P value of less than .05 requires replication in a second study that also yields outcomes with a P value of less than .05.
“If, however, you have a large single trial, you can win approval by meeting a standard of P less than .00125. The strength of the result of PARADIGM-HF, with a P of .0000004, is equivalent to between four and five single trials replicated at P less than .05. And for the endpoint of cardiovascular mortality, where the PARADIGM-HF result was significant at a P of .00008, that’s equivalent to between two and three trials replicated at P less than .05. So in my view PARADIGM-HF easily meets the criteria for a level IA indication,” said Dr. McMurray, professor of cardiology at the University of Glasgow.
He presented for the first time a new analysis with a major wow factor. This was an imputed placebo analysis providing the answer to a question many cardiologists have asked him since the presentation of the top-line PARADIGM-HF results in Barcelona: namely, how would LCZ696 have stacked up in a placebo-controlled trial?
Such a study wouldn’t be ethical now, of course, but it’s possible to make inferences by comparing LCZ696’s superiority to enalapril at 10 mg b.i.d. in PARADIGM-HF to enalapril’s performance at the same dose relative to placebo in the earlier 2,569-patient SOLVD-Treatment trial, which featured the same composite primary endpoint (N. Engl. J. Med. 1991;325:293-302).
In SOLVD-Treatment, enalapril resulted in a 28% relative risk reduction in the composite endpoint, compared with placebo. Through indirect comparison, LCZ696 would have an imputed 43% relative risk reduction, compared with placebo. For the endpoint of cardiovascular mortality, enalapril showed a 17% risk reduction relative to placebo; when the PARADIGM-HF results are factored in, this translates to an inferred 34% relative risk reduction for LCZ696 versus placebo.
Similarly, in the CHARM-Alternative trial (Lancet 2003;362:772-6), which featured 2,028 patients on more contemporary guideline–recommended background therapy than in SOLVD-Treatment, patients on the angiotensin receptor blocker candesartan showed a 23% relative risk reduction in the composite endpoint, compared with placebo, along with a 15% reduction in cardiovascular mortality. In the imputed placebo analysis, this translated to relative risk reductions of 49% and 34%, respectively, for LCZ696 versus placebo.
“We see a doubling in the reduction in cardiovascular mortality with this new therapy over and above that obtained with an ACE inhibitor or ARB [angiotensin receptor blocker],” Dr. McMurray emphasized.
Panelist Dr. Lynne W. Stevenson wasn’t convinced.
“I don’t believe it is time to replace ACE inhibitors and ARBs. I don’t think LCZ696 is ready for a level I [treatment should be performed] indication; that is a higher bar. ... I think we could see a level IIa [treatment is reasonable to perform] indication based on the strong results that we’ve seen,” said Dr. Stevenson, director of the heart failure and cardiomyopathy program at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.
She estimated that fewer than 10% of U.S. heart failure patients fit the description of PARADIGM-HF participants, with mild to moderate heart failure with reduced ejection fraction. Importantly, the run-in process employed in the study ensured that only patients with a demonstrated ability to tolerate enalapril in therapeutic doses were enrolled. And even in that filtered population, there was a substantial dropout rate in the LCZ696 arm due to hypotension during follow-up.
“I certainly don’t think we have any information about patients newly diagnosed with heart failure. I don’t think if you put new heart failure patients on LCZ696, they’d necessarily be able to stand up, and if they could stand up I’m not sure we could get them on the appropriate dose of beta blockers,” Dr. Stevenson added.
Noting that only 5% of PARADIGM-HF participants were black, she said that “clearly this is something we will need to watch as we get more experience with this drug, but there was no signal of concern.”
Dr. Marvin A. Konstam, professor of medicine at Tufts University, Boston, shared one of Dr. Stevenson’s concerns: “How do we know what will happen with ACE inhibitor virgins in the real world where you don’t get a run-in period?”
Panelist Dr. John G.F. Cleland said, “I don’t want to second-guess the guideline committees, but surely this must be a IA [data derived from multiple clinical trials or meta-analyses] indication. What intrigues me is what will the indication for ACE inhibitors look like in future guidelines? Is it also going to be IA in the same group of patients? That’s something the guidelines committees are going to have to sort out.”
“A lot of these questions and people’s concerns will either be increased or reduced once we start to get the medicine into clinical practice. What I find quite distressing is that we might be sitting here at this time next year and still not be in a position to prescribe this agent because it may still be going through the regulatory process,” said Dr. Cleland, professor of cardiology at the University of Hull (England).
LAS VEGAS – Additional findings from the landmark PARADIGM-HF trial presented at the annual meeting of the Heart Failure Society of America provided what many observers deemed a persuasive case for the novel angiotensin receptor neprilysin inhibitor known for now as LCZ696 as deserving of a level I indication in the next update of the major heart failure management guidelines.
At a special session added late to the meeting program in the wake of the spectacularly positive top-line results of PARADIGM-HF presented just a few weeks earlier at the European Society of Cardiology meeting in Barcelona, an international panel of heart failure heavyweights tackled questions about the study’s implications, including whether the results need replication in a second randomized controlled trial before LCZ696 can win regulatory approval. And once approved, should guidelines committees give it a level I, must-use indication? How applicable are the PARADIGM-HF results to the broader population of heart failure patients, and in particular black patients and older individuals with class III/IV heart failure? And what about patients with heart failure with preserved ejection fraction (HFpEF) ?
In other words, does PARADIGM-HF, with more than 8,400 randomized subjects, represent a true paradigm shift in heart failure management?
For coprincipal investigator Dr. Milton Packer, the answer is a resounding yes.
“For the past 25 years, the magnitude of the effect of ACE inhibitors on cardiovascular mortality – about an 18% reduction – has created an ethical mandate for their use in all patients with chronic heart failure who could tolerate treatment with these drugs. The finding that LCZ696 has a 20% greater effect on cardiovascular mortality than ACE inhibitors strongly supports the conclusion that LCZ696 should replace the current use of ACE inhibitors and angiotensin receptor blockers in the management of chronic heart failure,” said Dr. Packer, professor and chair of the department of clinical sciences at University of Texas Southwestern Medical Center, Dallas.
His coprincipal investigator, Dr. John J.V. McMurray, cited the statistical strength of the PARADIGM-HF results for the primary composite outcome of cardiovascular death or heart failure hospitalization, which had an extraordinary P value of .0000004, in making the case that the trial findings are sufficient to win regulatory approval without a confirmatory study.
He noted that the regulatory standard in the United States and Europe is that a positive clinical trial having a P value of less than .05 requires replication in a second study that also yields outcomes with a P value of less than .05.
“If, however, you have a large single trial, you can win approval by meeting a standard of P less than .00125. The strength of the result of PARADIGM-HF, with a P of .0000004, is equivalent to between four and five single trials replicated at P less than .05. And for the endpoint of cardiovascular mortality, where the PARADIGM-HF result was significant at a P of .00008, that’s equivalent to between two and three trials replicated at P less than .05. So in my view PARADIGM-HF easily meets the criteria for a level IA indication,” said Dr. McMurray, professor of cardiology at the University of Glasgow.
He presented for the first time a new analysis with a major wow factor. This was an imputed placebo analysis providing the answer to a question many cardiologists have asked him since the presentation of the top-line PARADIGM-HF results in Barcelona: namely, how would LCZ696 have stacked up in a placebo-controlled trial?
Such a study wouldn’t be ethical now, of course, but it’s possible to make inferences by comparing LCZ696’s superiority to enalapril at 10 mg b.i.d. in PARADIGM-HF to enalapril’s performance at the same dose relative to placebo in the earlier 2,569-patient SOLVD-Treatment trial, which featured the same composite primary endpoint (N. Engl. J. Med. 1991;325:293-302).
In SOLVD-Treatment, enalapril resulted in a 28% relative risk reduction in the composite endpoint, compared with placebo. Through indirect comparison, LCZ696 would have an imputed 43% relative risk reduction, compared with placebo. For the endpoint of cardiovascular mortality, enalapril showed a 17% risk reduction relative to placebo; when the PARADIGM-HF results are factored in, this translates to an inferred 34% relative risk reduction for LCZ696 versus placebo.
Similarly, in the CHARM-Alternative trial (Lancet 2003;362:772-6), which featured 2,028 patients on more contemporary guideline–recommended background therapy than in SOLVD-Treatment, patients on the angiotensin receptor blocker candesartan showed a 23% relative risk reduction in the composite endpoint, compared with placebo, along with a 15% reduction in cardiovascular mortality. In the imputed placebo analysis, this translated to relative risk reductions of 49% and 34%, respectively, for LCZ696 versus placebo.
“We see a doubling in the reduction in cardiovascular mortality with this new therapy over and above that obtained with an ACE inhibitor or ARB [angiotensin receptor blocker],” Dr. McMurray emphasized.
Panelist Dr. Lynne W. Stevenson wasn’t convinced.
“I don’t believe it is time to replace ACE inhibitors and ARBs. I don’t think LCZ696 is ready for a level I [treatment should be performed] indication; that is a higher bar. ... I think we could see a level IIa [treatment is reasonable to perform] indication based on the strong results that we’ve seen,” said Dr. Stevenson, director of the heart failure and cardiomyopathy program at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.
She estimated that fewer than 10% of U.S. heart failure patients fit the description of PARADIGM-HF participants, with mild to moderate heart failure with reduced ejection fraction. Importantly, the run-in process employed in the study ensured that only patients with a demonstrated ability to tolerate enalapril in therapeutic doses were enrolled. And even in that filtered population, there was a substantial dropout rate in the LCZ696 arm due to hypotension during follow-up.
“I certainly don’t think we have any information about patients newly diagnosed with heart failure. I don’t think if you put new heart failure patients on LCZ696, they’d necessarily be able to stand up, and if they could stand up I’m not sure we could get them on the appropriate dose of beta blockers,” Dr. Stevenson added.
Noting that only 5% of PARADIGM-HF participants were black, she said that “clearly this is something we will need to watch as we get more experience with this drug, but there was no signal of concern.”
Dr. Marvin A. Konstam, professor of medicine at Tufts University, Boston, shared one of Dr. Stevenson’s concerns: “How do we know what will happen with ACE inhibitor virgins in the real world where you don’t get a run-in period?”
Panelist Dr. John G.F. Cleland said, “I don’t want to second-guess the guideline committees, but surely this must be a IA [data derived from multiple clinical trials or meta-analyses] indication. What intrigues me is what will the indication for ACE inhibitors look like in future guidelines? Is it also going to be IA in the same group of patients? That’s something the guidelines committees are going to have to sort out.”
“A lot of these questions and people’s concerns will either be increased or reduced once we start to get the medicine into clinical practice. What I find quite distressing is that we might be sitting here at this time next year and still not be in a position to prescribe this agent because it may still be going through the regulatory process,” said Dr. Cleland, professor of cardiology at the University of Hull (England).
LAS VEGAS – Additional findings from the landmark PARADIGM-HF trial presented at the annual meeting of the Heart Failure Society of America provided what many observers deemed a persuasive case for the novel angiotensin receptor neprilysin inhibitor known for now as LCZ696 as deserving of a level I indication in the next update of the major heart failure management guidelines.
At a special session added late to the meeting program in the wake of the spectacularly positive top-line results of PARADIGM-HF presented just a few weeks earlier at the European Society of Cardiology meeting in Barcelona, an international panel of heart failure heavyweights tackled questions about the study’s implications, including whether the results need replication in a second randomized controlled trial before LCZ696 can win regulatory approval. And once approved, should guidelines committees give it a level I, must-use indication? How applicable are the PARADIGM-HF results to the broader population of heart failure patients, and in particular black patients and older individuals with class III/IV heart failure? And what about patients with heart failure with preserved ejection fraction (HFpEF) ?
In other words, does PARADIGM-HF, with more than 8,400 randomized subjects, represent a true paradigm shift in heart failure management?
For coprincipal investigator Dr. Milton Packer, the answer is a resounding yes.
“For the past 25 years, the magnitude of the effect of ACE inhibitors on cardiovascular mortality – about an 18% reduction – has created an ethical mandate for their use in all patients with chronic heart failure who could tolerate treatment with these drugs. The finding that LCZ696 has a 20% greater effect on cardiovascular mortality than ACE inhibitors strongly supports the conclusion that LCZ696 should replace the current use of ACE inhibitors and angiotensin receptor blockers in the management of chronic heart failure,” said Dr. Packer, professor and chair of the department of clinical sciences at University of Texas Southwestern Medical Center, Dallas.
His coprincipal investigator, Dr. John J.V. McMurray, cited the statistical strength of the PARADIGM-HF results for the primary composite outcome of cardiovascular death or heart failure hospitalization, which had an extraordinary P value of .0000004, in making the case that the trial findings are sufficient to win regulatory approval without a confirmatory study.
He noted that the regulatory standard in the United States and Europe is that a positive clinical trial having a P value of less than .05 requires replication in a second study that also yields outcomes with a P value of less than .05.
“If, however, you have a large single trial, you can win approval by meeting a standard of P less than .00125. The strength of the result of PARADIGM-HF, with a P of .0000004, is equivalent to between four and five single trials replicated at P less than .05. And for the endpoint of cardiovascular mortality, where the PARADIGM-HF result was significant at a P of .00008, that’s equivalent to between two and three trials replicated at P less than .05. So in my view PARADIGM-HF easily meets the criteria for a level IA indication,” said Dr. McMurray, professor of cardiology at the University of Glasgow.
He presented for the first time a new analysis with a major wow factor. This was an imputed placebo analysis providing the answer to a question many cardiologists have asked him since the presentation of the top-line PARADIGM-HF results in Barcelona: namely, how would LCZ696 have stacked up in a placebo-controlled trial?
Such a study wouldn’t be ethical now, of course, but it’s possible to make inferences by comparing LCZ696’s superiority to enalapril at 10 mg b.i.d. in PARADIGM-HF to enalapril’s performance at the same dose relative to placebo in the earlier 2,569-patient SOLVD-Treatment trial, which featured the same composite primary endpoint (N. Engl. J. Med. 1991;325:293-302).
In SOLVD-Treatment, enalapril resulted in a 28% relative risk reduction in the composite endpoint, compared with placebo. Through indirect comparison, LCZ696 would have an imputed 43% relative risk reduction, compared with placebo. For the endpoint of cardiovascular mortality, enalapril showed a 17% risk reduction relative to placebo; when the PARADIGM-HF results are factored in, this translates to an inferred 34% relative risk reduction for LCZ696 versus placebo.
Similarly, in the CHARM-Alternative trial (Lancet 2003;362:772-6), which featured 2,028 patients on more contemporary guideline–recommended background therapy than in SOLVD-Treatment, patients on the angiotensin receptor blocker candesartan showed a 23% relative risk reduction in the composite endpoint, compared with placebo, along with a 15% reduction in cardiovascular mortality. In the imputed placebo analysis, this translated to relative risk reductions of 49% and 34%, respectively, for LCZ696 versus placebo.
“We see a doubling in the reduction in cardiovascular mortality with this new therapy over and above that obtained with an ACE inhibitor or ARB [angiotensin receptor blocker],” Dr. McMurray emphasized.
Panelist Dr. Lynne W. Stevenson wasn’t convinced.
“I don’t believe it is time to replace ACE inhibitors and ARBs. I don’t think LCZ696 is ready for a level I [treatment should be performed] indication; that is a higher bar. ... I think we could see a level IIa [treatment is reasonable to perform] indication based on the strong results that we’ve seen,” said Dr. Stevenson, director of the heart failure and cardiomyopathy program at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.
She estimated that fewer than 10% of U.S. heart failure patients fit the description of PARADIGM-HF participants, with mild to moderate heart failure with reduced ejection fraction. Importantly, the run-in process employed in the study ensured that only patients with a demonstrated ability to tolerate enalapril in therapeutic doses were enrolled. And even in that filtered population, there was a substantial dropout rate in the LCZ696 arm due to hypotension during follow-up.
“I certainly don’t think we have any information about patients newly diagnosed with heart failure. I don’t think if you put new heart failure patients on LCZ696, they’d necessarily be able to stand up, and if they could stand up I’m not sure we could get them on the appropriate dose of beta blockers,” Dr. Stevenson added.
Noting that only 5% of PARADIGM-HF participants were black, she said that “clearly this is something we will need to watch as we get more experience with this drug, but there was no signal of concern.”
Dr. Marvin A. Konstam, professor of medicine at Tufts University, Boston, shared one of Dr. Stevenson’s concerns: “How do we know what will happen with ACE inhibitor virgins in the real world where you don’t get a run-in period?”
Panelist Dr. John G.F. Cleland said, “I don’t want to second-guess the guideline committees, but surely this must be a IA [data derived from multiple clinical trials or meta-analyses] indication. What intrigues me is what will the indication for ACE inhibitors look like in future guidelines? Is it also going to be IA in the same group of patients? That’s something the guidelines committees are going to have to sort out.”
“A lot of these questions and people’s concerns will either be increased or reduced once we start to get the medicine into clinical practice. What I find quite distressing is that we might be sitting here at this time next year and still not be in a position to prescribe this agent because it may still be going through the regulatory process,” said Dr. Cleland, professor of cardiology at the University of Hull (England).
EXPERT OPINION FROM THE HFSA ANNUAL SCIENTIFIC MEETING
What about LCZ696 for heart failure with preserved ejection fraction?
LAS VEGAS – Having scored a spectacular success with its investigational agent LCZ696 for the treatment of heart failure with reduced ejection fraction in the landmark PARADIGM-HF trial, Novartis has placed a large bet that it can do the same in patients with heart failure with preserved ejection fraction in the ongoing PARAGON trial.
The phase III study, which began this summer, will enroll roughly 4,300 patients with symptomatic heart failure with preserved ejection fraction (HFpEF) in 37 countries. They are being randomized to the novel, first-in-class angiotensin receptor neprilysin inhibitor (ARNI) known for now as LCZ696 at 200 mg b.i.d. or valsartan at 160 mg b.i.d., PARAGON principal investigator Dr. Scott D. Solomon explained at the annual meeting of the Heart Failure Society of America.
The study is a bit of a gamble because, to date, there is no effective treatment for HFpEF, which accounts for at least half of all cases of heart failure. Four prior major clinical trials testing various candidate therapies have all gone down in flames, failing to achieve their primary endpoints, but there are multiple reasons to believe PARAGON will be different, according to Dr. Solomon, professor of medicine at Harvard Medical School, Boston.
For one thing, previous major trials enrolled some participants without clear evidence that they even had HFpEF. Not so in PARAGON, which requires subjects to have symptomatic heart failure, an ejection fraction of 45% or more, and evidence of structural heart disease along with either a hospitalization for heart failure within the previous 9 months or elevated natriuretic peptides.
Also, unlike the prior disappointing studies involving other agents, PARAGON is supported by positive findings in a phase II proof-of-concept study. In the phase II, double-blind PARAMOUNT trial, also led by Dr. Solomon, 301 patients with HFpEF were randomized to LCZ696 or valsartan for 36 weeks. The primary study endpoint was change in N-terminal of the prohormone brain natriuretic hormone (NT-proBNP), a biomarker of left ventricular wall stress, through 12 weeks. The result was positive, with a 23% greater reduction in elevated baseline levels in the LCZ696 group, compared with those on valsartan (Lancet 2012;380:1387-95).
By 36 weeks, the ARNI-treated patients also showed a significant reduction in left atrial volume as well as improvement in New York Heart Association functional class, the cardiologist added.
PARAGON features a novel primary endpoint: a composite of cardiovascular death and total hospitalizations for heart failure, rather than time to the first hospitalization, as used in previous trials. “Total hospitalizations for heart failure better captures the full burden of the disease,” Dr. Solomon explained.
Results of PARAGON are expected in 2019.
Dr. Solomon has received research grants and honoraria from Novartis, which is funding the PARAGON trial.
LAS VEGAS – Having scored a spectacular success with its investigational agent LCZ696 for the treatment of heart failure with reduced ejection fraction in the landmark PARADIGM-HF trial, Novartis has placed a large bet that it can do the same in patients with heart failure with preserved ejection fraction in the ongoing PARAGON trial.
The phase III study, which began this summer, will enroll roughly 4,300 patients with symptomatic heart failure with preserved ejection fraction (HFpEF) in 37 countries. They are being randomized to the novel, first-in-class angiotensin receptor neprilysin inhibitor (ARNI) known for now as LCZ696 at 200 mg b.i.d. or valsartan at 160 mg b.i.d., PARAGON principal investigator Dr. Scott D. Solomon explained at the annual meeting of the Heart Failure Society of America.
The study is a bit of a gamble because, to date, there is no effective treatment for HFpEF, which accounts for at least half of all cases of heart failure. Four prior major clinical trials testing various candidate therapies have all gone down in flames, failing to achieve their primary endpoints, but there are multiple reasons to believe PARAGON will be different, according to Dr. Solomon, professor of medicine at Harvard Medical School, Boston.
For one thing, previous major trials enrolled some participants without clear evidence that they even had HFpEF. Not so in PARAGON, which requires subjects to have symptomatic heart failure, an ejection fraction of 45% or more, and evidence of structural heart disease along with either a hospitalization for heart failure within the previous 9 months or elevated natriuretic peptides.
Also, unlike the prior disappointing studies involving other agents, PARAGON is supported by positive findings in a phase II proof-of-concept study. In the phase II, double-blind PARAMOUNT trial, also led by Dr. Solomon, 301 patients with HFpEF were randomized to LCZ696 or valsartan for 36 weeks. The primary study endpoint was change in N-terminal of the prohormone brain natriuretic hormone (NT-proBNP), a biomarker of left ventricular wall stress, through 12 weeks. The result was positive, with a 23% greater reduction in elevated baseline levels in the LCZ696 group, compared with those on valsartan (Lancet 2012;380:1387-95).
By 36 weeks, the ARNI-treated patients also showed a significant reduction in left atrial volume as well as improvement in New York Heart Association functional class, the cardiologist added.
PARAGON features a novel primary endpoint: a composite of cardiovascular death and total hospitalizations for heart failure, rather than time to the first hospitalization, as used in previous trials. “Total hospitalizations for heart failure better captures the full burden of the disease,” Dr. Solomon explained.
Results of PARAGON are expected in 2019.
Dr. Solomon has received research grants and honoraria from Novartis, which is funding the PARAGON trial.
LAS VEGAS – Having scored a spectacular success with its investigational agent LCZ696 for the treatment of heart failure with reduced ejection fraction in the landmark PARADIGM-HF trial, Novartis has placed a large bet that it can do the same in patients with heart failure with preserved ejection fraction in the ongoing PARAGON trial.
The phase III study, which began this summer, will enroll roughly 4,300 patients with symptomatic heart failure with preserved ejection fraction (HFpEF) in 37 countries. They are being randomized to the novel, first-in-class angiotensin receptor neprilysin inhibitor (ARNI) known for now as LCZ696 at 200 mg b.i.d. or valsartan at 160 mg b.i.d., PARAGON principal investigator Dr. Scott D. Solomon explained at the annual meeting of the Heart Failure Society of America.
The study is a bit of a gamble because, to date, there is no effective treatment for HFpEF, which accounts for at least half of all cases of heart failure. Four prior major clinical trials testing various candidate therapies have all gone down in flames, failing to achieve their primary endpoints, but there are multiple reasons to believe PARAGON will be different, according to Dr. Solomon, professor of medicine at Harvard Medical School, Boston.
For one thing, previous major trials enrolled some participants without clear evidence that they even had HFpEF. Not so in PARAGON, which requires subjects to have symptomatic heart failure, an ejection fraction of 45% or more, and evidence of structural heart disease along with either a hospitalization for heart failure within the previous 9 months or elevated natriuretic peptides.
Also, unlike the prior disappointing studies involving other agents, PARAGON is supported by positive findings in a phase II proof-of-concept study. In the phase II, double-blind PARAMOUNT trial, also led by Dr. Solomon, 301 patients with HFpEF were randomized to LCZ696 or valsartan for 36 weeks. The primary study endpoint was change in N-terminal of the prohormone brain natriuretic hormone (NT-proBNP), a biomarker of left ventricular wall stress, through 12 weeks. The result was positive, with a 23% greater reduction in elevated baseline levels in the LCZ696 group, compared with those on valsartan (Lancet 2012;380:1387-95).
By 36 weeks, the ARNI-treated patients also showed a significant reduction in left atrial volume as well as improvement in New York Heart Association functional class, the cardiologist added.
PARAGON features a novel primary endpoint: a composite of cardiovascular death and total hospitalizations for heart failure, rather than time to the first hospitalization, as used in previous trials. “Total hospitalizations for heart failure better captures the full burden of the disease,” Dr. Solomon explained.
Results of PARAGON are expected in 2019.
Dr. Solomon has received research grants and honoraria from Novartis, which is funding the PARAGON trial.
EXPERT ANALYSIS FROM THE HFSA ANNUAL SCIENTIFIC MEETING