Heart Failure

SAN FRANCISCO – Handheld ultrasound proved "vastly superior" to physical examination conducted by cardiologists for the evaluation of a variety of cardiovascular complaints in a head-to-head prospective trial.

All 250 study participants underwent a clinically indicated standard 2-D and Doppler transthoracic echocardiography exam. But first they received an initial clinical assessment with both a point-of-care, handheld ultrasound scan and a physical exam performed by randomly assigned cardiologists who had widely varying degrees of experience. The cardiologists’ physical exam took an average of 5 minutes, while the limited ultrasound evaluation performed with the commercially available VScan device took a mean of 8.2 minutes, Dr. Manish Mehta reported at the annual meeting of the American College of Cardiology.

Ultrasound had a far higher correct-diagnosis rate than did cardiologists’ physical exam for nearly all of the heart conditions the cardiologists encountered. For example, ultrasound correctly diagnosed moderate or severe mitral regurgitation as confirmed by standard echocardiography in 20 of 20 affected patients, compared with 12 of 20 diagnosed correctly as a result of the physical exam. Ultrasound was threefold more accurate than was physical exam in diagnosis of left ventricular dysfunction in the 54 affected patients. It was also significantly more accurate in the diagnosis of right ventricular dysfunction, tricuspid regurgitation, moderate or severe valve abnormalities, and a miscellaneous category comprising 107 patients with pleural, pericardial, aortic, or congenital heart disease.

In the other two diagnostic categories – pulmonary hypertension and elevated right atrial pressure – ultrasound outperformed physical exam, but not by a statistically significant margin, added Dr. Mehta of Oregon Health and Science University, Portland.

"Routine incorporation of a hand-carried ultrasound device into the physical exam facilitates early and accurate diagnosis of cardiac pathology, which can result in more efficient delivery of care and [can] potentially reduce cost," he concluded.

Dr. Mehta said he and his coinvestigators conducted this study because hand-carried ultrasound has not caught on in cardiology practice to date the way they feel it should. They wanted to provide further supporting evidence for its routine use.

The study was funded by GE Healthcare, which markets the VScan system. Dr. Mehta reported having no financial conflicts.

bjancin@frontlinemedcom.com

SAN FRANCISCO – Handheld ultrasound proved "vastly superior" to physical examination conducted by cardiologists for the evaluation of a variety of cardiovascular complaints in a head-to-head prospective trial.

All 250 study participants underwent a clinically indicated standard 2-D and Doppler transthoracic echocardiography exam. But first they received an initial clinical assessment with both a point-of-care, handheld ultrasound scan and a physical exam performed by randomly assigned cardiologists who had widely varying degrees of experience. The cardiologists’ physical exam took an average of 5 minutes, while the limited ultrasound evaluation performed with the commercially available VScan device took a mean of 8.2 minutes, Dr. Manish Mehta reported at the annual meeting of the American College of Cardiology.

Ultrasound had a far higher correct-diagnosis rate than did cardiologists’ physical exam for nearly all of the heart conditions the cardiologists encountered. For example, ultrasound correctly diagnosed moderate or severe mitral regurgitation as confirmed by standard echocardiography in 20 of 20 affected patients, compared with 12 of 20 diagnosed correctly as a result of the physical exam. Ultrasound was threefold more accurate than was physical exam in diagnosis of left ventricular dysfunction in the 54 affected patients. It was also significantly more accurate in the diagnosis of right ventricular dysfunction, tricuspid regurgitation, moderate or severe valve abnormalities, and a miscellaneous category comprising 107 patients with pleural, pericardial, aortic, or congenital heart disease.

In the other two diagnostic categories – pulmonary hypertension and elevated right atrial pressure – ultrasound outperformed physical exam, but not by a statistically significant margin, added Dr. Mehta of Oregon Health and Science University, Portland.

"Routine incorporation of a hand-carried ultrasound device into the physical exam facilitates early and accurate diagnosis of cardiac pathology, which can result in more efficient delivery of care and [can] potentially reduce cost," he concluded.

Dr. Mehta said he and his coinvestigators conducted this study because hand-carried ultrasound has not caught on in cardiology practice to date the way they feel it should. They wanted to provide further supporting evidence for its routine use.

The study was funded by GE Healthcare, which markets the VScan system. Dr. Mehta reported having no financial conflicts.

bjancin@frontlinemedcom.com

SAN FRANCISCO – Handheld ultrasound proved "vastly superior" to physical examination conducted by cardiologists for the evaluation of a variety of cardiovascular complaints in a head-to-head prospective trial.

All 250 study participants underwent a clinically indicated standard 2-D and Doppler transthoracic echocardiography exam. But first they received an initial clinical assessment with both a point-of-care, handheld ultrasound scan and a physical exam performed by randomly assigned cardiologists who had widely varying degrees of experience. The cardiologists’ physical exam took an average of 5 minutes, while the limited ultrasound evaluation performed with the commercially available VScan device took a mean of 8.2 minutes, Dr. Manish Mehta reported at the annual meeting of the American College of Cardiology.

Ultrasound had a far higher correct-diagnosis rate than did cardiologists’ physical exam for nearly all of the heart conditions the cardiologists encountered. For example, ultrasound correctly diagnosed moderate or severe mitral regurgitation as confirmed by standard echocardiography in 20 of 20 affected patients, compared with 12 of 20 diagnosed correctly as a result of the physical exam. Ultrasound was threefold more accurate than was physical exam in diagnosis of left ventricular dysfunction in the 54 affected patients. It was also significantly more accurate in the diagnosis of right ventricular dysfunction, tricuspid regurgitation, moderate or severe valve abnormalities, and a miscellaneous category comprising 107 patients with pleural, pericardial, aortic, or congenital heart disease.

In the other two diagnostic categories – pulmonary hypertension and elevated right atrial pressure – ultrasound outperformed physical exam, but not by a statistically significant margin, added Dr. Mehta of Oregon Health and Science University, Portland.

"Routine incorporation of a hand-carried ultrasound device into the physical exam facilitates early and accurate diagnosis of cardiac pathology, which can result in more efficient delivery of care and [can] potentially reduce cost," he concluded.

Dr. Mehta said he and his coinvestigators conducted this study because hand-carried ultrasound has not caught on in cardiology practice to date the way they feel it should. They wanted to provide further supporting evidence for its routine use.

The study was funded by GE Healthcare, which markets the VScan system. Dr. Mehta reported having no financial conflicts.

bjancin@frontlinemedcom.com

One of the late-breaker reports at the American College of Cardiology’s annual meeting in March had results from a post hoc analysis of 16-year-old data from the DIG trial, by far the largest study to ever assess digoxin for heart failure, a treatment that precipitously dropped out of favor during the decade following the initial DIG report in 1997. Not your typical back story for a late breaker.

The researchers who ran the new analysis of the old DIG data also took what seem like two sizable leaps by framing their new look as a way to get a sense whether digoxin treatment could cut the large number of Medicare patients with heart failure who need rehospitalization within a month after a hospital discharge.

Courtesy of Wikimedia Commons

Dr. Ali Ahmed, a cardiologist from the University of Alabama, Birmingham, who presented this ACC late breaker, noted how clinicians and hospital officials are eager to find safe and effective treatments for cutting heart failure readmissions, especially since last Oct. 1 when the Centers for Medicare and Medicaid Services began penalizing hospitals that accumulate high heart failure readmission numbers.

One leap was that the patients in the 1990s enrolled in the Digitalis Investigation Group (DIG) trial all had chronic, stable heart failure, without recent hospitalization. Although the post hoc analysis that Dr. Ahmed presented showed that the half of the DIG patients who were aged 65 or older had their heart failure hospitalization rate cut by a third while on digoxin, compared with patients on placebo, a statistically significant difference for the analysis’ primary endpoint, Dr. Ahmed admitted in his talk that the relevance of his findings to the new Medicare penalties was doubly limited. First, because the DIG population comprised ambulatory patients rather than ones just out of the hospital, and second because the endpoint examined in DIG was index hospital admission rather than readmission. Two pretty important differences.

On top of that, many heart failure experts who heard the results were quick to question the meaning in 2013 of data collected from heart failure patients back in the mid-1990s whose background regimens completely lacked beta-blockers, aldosterone receptor antagonists (spironolactone and eplerenone), and implanted cardiac devices, treatments that have since become cornerstones of heart failure management.

Digoxin "is not a therapy we should embrace wholeheartedly until there is a new trial with contemporary management," commented Dr. Mariell L. Jessup, a heart failure specialist at the University of Pennsylvania, Philadelphia, who cochaired the late-breaker session in which Dr. Ahmed spoke.

But if it was so questionable to use 16-year old, clearly outdated data to address in a post hoc way an issue – 30-day hospital readmissions for heart failure – with at best tangential relevance to what was examined in the DIG trial, what else might be behind this curious report from a large group of prominent heart-failure specialists? (You can see all their names in the article published online simultaneous to Dr. Ahmed’s ACC report [Am. J. Med. 2013;126 (doi:10.1016/j.amjmed.2013.02.001)]).

The answer seems to be their desire to promote digoxin, keep it current in cardiology chatter, and build pressure for a new, prospective study that reexamines the incremental benefit of digoxin on top everything else that heart failure patients receive today. They see current heart failure management, especially efforts to cut hospitalizations for acute decompensation and also cut the rate at which decompensated patients wind up back in the hospital a second time, as woefully inadequate and stand discouraged after many new agents have failed to make a dent in this problem.

"Dismissing digoxin, which was approved by the FDA only 10 years ago and has been used for 2,000 years, in the face of a high event rate [among heart failure patients] when we cannot find any new drugs, is not a wise clinical decision," said Dr. Mihai Gheorghiade, a cardiologist with Northwestern University, Evanston, Ill., who coauthored the new analysis and is a leader of the movement to resurrect digoxin. Using digoxin "isn’t controversial if you see benefit from it and if we are desperate to find something for these patients," he said during a press conference at the meeting.

Efforts to rehabilitate and reevaluate digoxin in heart failure have been going on since the mid-2000s. Dr. Ahmed, Dr. Gheorghiade, and their associates published their first reanalysis of the DIG data in 2005 (Eur. Heart J. 2006;27:178-86), which was recognized by an editorialist at the time as a call to "rehabilitate" digoxin (Eur. Heart J. 2006;27:127-9). In 2006, Dr. Gheorghiade lamented digoxin’s neglect and fall from standard heart failure management, having been muscled out by treatments with big-pocket backers – beta-blockers, ACE inhibitors, and cardiac resynchronization devices; concerns over digoxin’s safety (which he says is obviated by using low dosages), and most of all the absence of any company with enough of a financial interest in digoxin to promote it and fund more studies (Circulation 2006;113:2556-64).

Houston heart failure expert Dr. Biykem Bozkurt saw the new DIG analysis as part of this decade-long rehabilitation effort. The new analysis "is a call for the reexamination of digoxin in acute heart failure," she said as an ACC panelist who discussed the study.

Digoxin’s proponents seem to recognize their big challenge: A large, new study of dioxin on top of today’s standard treatments is the key to convincing skeptical colleagues, but who will pay for it? "The problem with digoxin is that no company sponsors it," Dr. Gheorghiade said.

mzoler@frontlinemedcom.com

Twitter @mitchelzoler

One of the late-breaker reports at the American College of Cardiology’s annual meeting in March had results from a post hoc analysis of 16-year-old data from the DIG trial, by far the largest study to ever assess digoxin for heart failure, a treatment that precipitously dropped out of favor during the decade following the initial DIG report in 1997. Not your typical back story for a late breaker.

The researchers who ran the new analysis of the old DIG data also took what seem like two sizable leaps by framing their new look as a way to get a sense whether digoxin treatment could cut the large number of Medicare patients with heart failure who need rehospitalization within a month after a hospital discharge.

Courtesy of Wikimedia Commons

Dr. Ali Ahmed, a cardiologist from the University of Alabama, Birmingham, who presented this ACC late breaker, noted how clinicians and hospital officials are eager to find safe and effective treatments for cutting heart failure readmissions, especially since last Oct. 1 when the Centers for Medicare and Medicaid Services began penalizing hospitals that accumulate high heart failure readmission numbers.

One leap was that the patients in the 1990s enrolled in the Digitalis Investigation Group (DIG) trial all had chronic, stable heart failure, without recent hospitalization. Although the post hoc analysis that Dr. Ahmed presented showed that the half of the DIG patients who were aged 65 or older had their heart failure hospitalization rate cut by a third while on digoxin, compared with patients on placebo, a statistically significant difference for the analysis’ primary endpoint, Dr. Ahmed admitted in his talk that the relevance of his findings to the new Medicare penalties was doubly limited. First, because the DIG population comprised ambulatory patients rather than ones just out of the hospital, and second because the endpoint examined in DIG was index hospital admission rather than readmission. Two pretty important differences.

On top of that, many heart failure experts who heard the results were quick to question the meaning in 2013 of data collected from heart failure patients back in the mid-1990s whose background regimens completely lacked beta-blockers, aldosterone receptor antagonists (spironolactone and eplerenone), and implanted cardiac devices, treatments that have since become cornerstones of heart failure management.

Digoxin "is not a therapy we should embrace wholeheartedly until there is a new trial with contemporary management," commented Dr. Mariell L. Jessup, a heart failure specialist at the University of Pennsylvania, Philadelphia, who cochaired the late-breaker session in which Dr. Ahmed spoke.

But if it was so questionable to use 16-year old, clearly outdated data to address in a post hoc way an issue – 30-day hospital readmissions for heart failure – with at best tangential relevance to what was examined in the DIG trial, what else might be behind this curious report from a large group of prominent heart-failure specialists? (You can see all their names in the article published online simultaneous to Dr. Ahmed’s ACC report [Am. J. Med. 2013;126 (doi:10.1016/j.amjmed.2013.02.001)]).

The answer seems to be their desire to promote digoxin, keep it current in cardiology chatter, and build pressure for a new, prospective study that reexamines the incremental benefit of digoxin on top everything else that heart failure patients receive today. They see current heart failure management, especially efforts to cut hospitalizations for acute decompensation and also cut the rate at which decompensated patients wind up back in the hospital a second time, as woefully inadequate and stand discouraged after many new agents have failed to make a dent in this problem.

"Dismissing digoxin, which was approved by the FDA only 10 years ago and has been used for 2,000 years, in the face of a high event rate [among heart failure patients] when we cannot find any new drugs, is not a wise clinical decision," said Dr. Mihai Gheorghiade, a cardiologist with Northwestern University, Evanston, Ill., who coauthored the new analysis and is a leader of the movement to resurrect digoxin. Using digoxin "isn’t controversial if you see benefit from it and if we are desperate to find something for these patients," he said during a press conference at the meeting.

Efforts to rehabilitate and reevaluate digoxin in heart failure have been going on since the mid-2000s. Dr. Ahmed, Dr. Gheorghiade, and their associates published their first reanalysis of the DIG data in 2005 (Eur. Heart J. 2006;27:178-86), which was recognized by an editorialist at the time as a call to "rehabilitate" digoxin (Eur. Heart J. 2006;27:127-9). In 2006, Dr. Gheorghiade lamented digoxin’s neglect and fall from standard heart failure management, having been muscled out by treatments with big-pocket backers – beta-blockers, ACE inhibitors, and cardiac resynchronization devices; concerns over digoxin’s safety (which he says is obviated by using low dosages), and most of all the absence of any company with enough of a financial interest in digoxin to promote it and fund more studies (Circulation 2006;113:2556-64).

Houston heart failure expert Dr. Biykem Bozkurt saw the new DIG analysis as part of this decade-long rehabilitation effort. The new analysis "is a call for the reexamination of digoxin in acute heart failure," she said as an ACC panelist who discussed the study.

Digoxin’s proponents seem to recognize their big challenge: A large, new study of dioxin on top of today’s standard treatments is the key to convincing skeptical colleagues, but who will pay for it? "The problem with digoxin is that no company sponsors it," Dr. Gheorghiade said.

mzoler@frontlinemedcom.com

Twitter @mitchelzoler

One of the late-breaker reports at the American College of Cardiology’s annual meeting in March had results from a post hoc analysis of 16-year-old data from the DIG trial, by far the largest study to ever assess digoxin for heart failure, a treatment that precipitously dropped out of favor during the decade following the initial DIG report in 1997. Not your typical back story for a late breaker.

The researchers who ran the new analysis of the old DIG data also took what seem like two sizable leaps by framing their new look as a way to get a sense whether digoxin treatment could cut the large number of Medicare patients with heart failure who need rehospitalization within a month after a hospital discharge.

Courtesy of Wikimedia Commons

Dr. Ali Ahmed, a cardiologist from the University of Alabama, Birmingham, who presented this ACC late breaker, noted how clinicians and hospital officials are eager to find safe and effective treatments for cutting heart failure readmissions, especially since last Oct. 1 when the Centers for Medicare and Medicaid Services began penalizing hospitals that accumulate high heart failure readmission numbers.

One leap was that the patients in the 1990s enrolled in the Digitalis Investigation Group (DIG) trial all had chronic, stable heart failure, without recent hospitalization. Although the post hoc analysis that Dr. Ahmed presented showed that the half of the DIG patients who were aged 65 or older had their heart failure hospitalization rate cut by a third while on digoxin, compared with patients on placebo, a statistically significant difference for the analysis’ primary endpoint, Dr. Ahmed admitted in his talk that the relevance of his findings to the new Medicare penalties was doubly limited. First, because the DIG population comprised ambulatory patients rather than ones just out of the hospital, and second because the endpoint examined in DIG was index hospital admission rather than readmission. Two pretty important differences.

On top of that, many heart failure experts who heard the results were quick to question the meaning in 2013 of data collected from heart failure patients back in the mid-1990s whose background regimens completely lacked beta-blockers, aldosterone receptor antagonists (spironolactone and eplerenone), and implanted cardiac devices, treatments that have since become cornerstones of heart failure management.

Digoxin "is not a therapy we should embrace wholeheartedly until there is a new trial with contemporary management," commented Dr. Mariell L. Jessup, a heart failure specialist at the University of Pennsylvania, Philadelphia, who cochaired the late-breaker session in which Dr. Ahmed spoke.

But if it was so questionable to use 16-year old, clearly outdated data to address in a post hoc way an issue – 30-day hospital readmissions for heart failure – with at best tangential relevance to what was examined in the DIG trial, what else might be behind this curious report from a large group of prominent heart-failure specialists? (You can see all their names in the article published online simultaneous to Dr. Ahmed’s ACC report [Am. J. Med. 2013;126 (doi:10.1016/j.amjmed.2013.02.001)]).

The answer seems to be their desire to promote digoxin, keep it current in cardiology chatter, and build pressure for a new, prospective study that reexamines the incremental benefit of digoxin on top everything else that heart failure patients receive today. They see current heart failure management, especially efforts to cut hospitalizations for acute decompensation and also cut the rate at which decompensated patients wind up back in the hospital a second time, as woefully inadequate and stand discouraged after many new agents have failed to make a dent in this problem.

"Dismissing digoxin, which was approved by the FDA only 10 years ago and has been used for 2,000 years, in the face of a high event rate [among heart failure patients] when we cannot find any new drugs, is not a wise clinical decision," said Dr. Mihai Gheorghiade, a cardiologist with Northwestern University, Evanston, Ill., who coauthored the new analysis and is a leader of the movement to resurrect digoxin. Using digoxin "isn’t controversial if you see benefit from it and if we are desperate to find something for these patients," he said during a press conference at the meeting.

Efforts to rehabilitate and reevaluate digoxin in heart failure have been going on since the mid-2000s. Dr. Ahmed, Dr. Gheorghiade, and their associates published their first reanalysis of the DIG data in 2005 (Eur. Heart J. 2006;27:178-86), which was recognized by an editorialist at the time as a call to "rehabilitate" digoxin (Eur. Heart J. 2006;27:127-9). In 2006, Dr. Gheorghiade lamented digoxin’s neglect and fall from standard heart failure management, having been muscled out by treatments with big-pocket backers – beta-blockers, ACE inhibitors, and cardiac resynchronization devices; concerns over digoxin’s safety (which he says is obviated by using low dosages), and most of all the absence of any company with enough of a financial interest in digoxin to promote it and fund more studies (Circulation 2006;113:2556-64).

Houston heart failure expert Dr. Biykem Bozkurt saw the new DIG analysis as part of this decade-long rehabilitation effort. The new analysis "is a call for the reexamination of digoxin in acute heart failure," she said as an ACC panelist who discussed the study.

Digoxin’s proponents seem to recognize their big challenge: A large, new study of dioxin on top of today’s standard treatments is the key to convincing skeptical colleagues, but who will pay for it? "The problem with digoxin is that no company sponsors it," Dr. Gheorghiade said.

mzoler@frontlinemedcom.com

Twitter @mitchelzoler

SAN FRANCISCO – Targeting a comprehensive cardiac-risk reduction program to adults with elevated natriuretic peptide significantly cut the rate of new left ventricular dysfunction, heart failure, and other cardiovascular events in a randomized trial with more than 1,300 patients.

"I think it was the structure of the intervention, the cohesion of care, rather than a specific intervention" that improved clinical outcomes, Dr. Kenneth M. McDonald said at the annual meeting of the American College of Cardiology. "Undoubtedly, a patient’s knowledge [of a high B-type natriuretic peptide level] improved their adherence to therapy." He and his associates ran the study at 39 primary care practices around Dublin that worked in collaboration with the cardiology department at St. Vincent’s University Hospital in Dublin.

Mitchel L. Zoler/IMNG Medical Media

The primary care physicians looked for patients at least 40 years old with at least one identified cardiovascular risk factor whose B-type natriuretic peptide (BNP) level rose above 50 pg/mL on an annual screening test. They referred these patients to St. Vincent’s for an intensified testing and management program similar to "the disease management structure we’ve used for several years for patients with heart failure," said Dr. McDonald, a professor of cardiology at St. Vincent’s and director of the heart failure unit. The program included a cardiology review and regular follow-up, echocardiography with Doppler and other cardiovascular investigations as needed, and nurse coaching.

"Routine BNP screening is not recommended in current guidelines. Perhaps this finding is the first step to get guidelines committees to address the use of BNP for screening," commented Dr. Sanjay Kaul, director of the vascular physiology and thrombosis research laboratory at the Burns and Allen Research Institute at Cedars Sinai Medical Center in Los Angeles.

Among the 1,374 patients enrolled in the STOP-HF (Screening to Prevent Heart Failure) trial, annual BNP measurement found 498 (36%) with a BNP level that rose above 50 pg/mL in at least one annual test. This included 235 patients randomized to the control arm and 263 randomized to the intervention group. The overall age of patients in the study averaged 65 years, but the age of those with elevated BNP averaged closer to 70 years.

During average follow-up of just over 4 years, patients referred to the cardiology program had 25 cases (10%) of heart failure or asymptomatic left ventricular dysfunction, compared with 44 cases (19%) in the control arm, a 54% odds ratio reduction that was statistically significant for the study’s primary endpoint. For the entire study group of 1,374 randomized patients, participation in the group eligible for referred care cut the primary endpoint by a relative 41%, compared with the controls, a statistically significant difference.

Mitchel L. Zoler/IMNG Medical Media

A secondary efficacy analysis that tallied the combined rate of incident heart failure, arrhythmia, myocardial infarction, unstable angina, cerebrovascular events, peripheral thrombosis, or pulmonary embolism found 51 events (7%) in the entire intervention group compared with 71 events (10%) in the control group, a 46% odds rate reduction that was statistically significant.

A study limitation was the large percentage of patients in both arms either lost to follow-up, 10%; or who withdrew their consent to participate, another 16%. "It challenges interpretation of the results," commented Dr. Kaul.

But Dr. McDonald and his associates were convinced by their findings.

"We believe the results are conclusive enough to roll this out as a clinical program," he said in an interview. "We are now extending this to another region of Ireland, and we will try to get this disseminated nationally."

He also foresees additional refinements to the program, possibly identifying other risk markers that can compliment BNP and further focus intervention.

"We have shown benefit, but a question is the cost of getting that benefit. BNP is clearly a step up from where we were, but that doesn’t mean we are as good as we could make it."

Dr. McDonald said that he had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

SAN FRANCISCO – Targeting a comprehensive cardiac-risk reduction program to adults with elevated natriuretic peptide significantly cut the rate of new left ventricular dysfunction, heart failure, and other cardiovascular events in a randomized trial with more than 1,300 patients.

"I think it was the structure of the intervention, the cohesion of care, rather than a specific intervention" that improved clinical outcomes, Dr. Kenneth M. McDonald said at the annual meeting of the American College of Cardiology. "Undoubtedly, a patient’s knowledge [of a high B-type natriuretic peptide level] improved their adherence to therapy." He and his associates ran the study at 39 primary care practices around Dublin that worked in collaboration with the cardiology department at St. Vincent’s University Hospital in Dublin.

Mitchel L. Zoler/IMNG Medical Media

The primary care physicians looked for patients at least 40 years old with at least one identified cardiovascular risk factor whose B-type natriuretic peptide (BNP) level rose above 50 pg/mL on an annual screening test. They referred these patients to St. Vincent’s for an intensified testing and management program similar to "the disease management structure we’ve used for several years for patients with heart failure," said Dr. McDonald, a professor of cardiology at St. Vincent’s and director of the heart failure unit. The program included a cardiology review and regular follow-up, echocardiography with Doppler and other cardiovascular investigations as needed, and nurse coaching.

"Routine BNP screening is not recommended in current guidelines. Perhaps this finding is the first step to get guidelines committees to address the use of BNP for screening," commented Dr. Sanjay Kaul, director of the vascular physiology and thrombosis research laboratory at the Burns and Allen Research Institute at Cedars Sinai Medical Center in Los Angeles.

Among the 1,374 patients enrolled in the STOP-HF (Screening to Prevent Heart Failure) trial, annual BNP measurement found 498 (36%) with a BNP level that rose above 50 pg/mL in at least one annual test. This included 235 patients randomized to the control arm and 263 randomized to the intervention group. The overall age of patients in the study averaged 65 years, but the age of those with elevated BNP averaged closer to 70 years.

During average follow-up of just over 4 years, patients referred to the cardiology program had 25 cases (10%) of heart failure or asymptomatic left ventricular dysfunction, compared with 44 cases (19%) in the control arm, a 54% odds ratio reduction that was statistically significant for the study’s primary endpoint. For the entire study group of 1,374 randomized patients, participation in the group eligible for referred care cut the primary endpoint by a relative 41%, compared with the controls, a statistically significant difference.

Mitchel L. Zoler/IMNG Medical Media

A secondary efficacy analysis that tallied the combined rate of incident heart failure, arrhythmia, myocardial infarction, unstable angina, cerebrovascular events, peripheral thrombosis, or pulmonary embolism found 51 events (7%) in the entire intervention group compared with 71 events (10%) in the control group, a 46% odds rate reduction that was statistically significant.

A study limitation was the large percentage of patients in both arms either lost to follow-up, 10%; or who withdrew their consent to participate, another 16%. "It challenges interpretation of the results," commented Dr. Kaul.

But Dr. McDonald and his associates were convinced by their findings.

"We believe the results are conclusive enough to roll this out as a clinical program," he said in an interview. "We are now extending this to another region of Ireland, and we will try to get this disseminated nationally."

He also foresees additional refinements to the program, possibly identifying other risk markers that can compliment BNP and further focus intervention.

"We have shown benefit, but a question is the cost of getting that benefit. BNP is clearly a step up from where we were, but that doesn’t mean we are as good as we could make it."

Dr. McDonald said that he had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

SAN FRANCISCO – Targeting a comprehensive cardiac-risk reduction program to adults with elevated natriuretic peptide significantly cut the rate of new left ventricular dysfunction, heart failure, and other cardiovascular events in a randomized trial with more than 1,300 patients.

"I think it was the structure of the intervention, the cohesion of care, rather than a specific intervention" that improved clinical outcomes, Dr. Kenneth M. McDonald said at the annual meeting of the American College of Cardiology. "Undoubtedly, a patient’s knowledge [of a high B-type natriuretic peptide level] improved their adherence to therapy." He and his associates ran the study at 39 primary care practices around Dublin that worked in collaboration with the cardiology department at St. Vincent’s University Hospital in Dublin.

Mitchel L. Zoler/IMNG Medical Media

The primary care physicians looked for patients at least 40 years old with at least one identified cardiovascular risk factor whose B-type natriuretic peptide (BNP) level rose above 50 pg/mL on an annual screening test. They referred these patients to St. Vincent’s for an intensified testing and management program similar to "the disease management structure we’ve used for several years for patients with heart failure," said Dr. McDonald, a professor of cardiology at St. Vincent’s and director of the heart failure unit. The program included a cardiology review and regular follow-up, echocardiography with Doppler and other cardiovascular investigations as needed, and nurse coaching.

"Routine BNP screening is not recommended in current guidelines. Perhaps this finding is the first step to get guidelines committees to address the use of BNP for screening," commented Dr. Sanjay Kaul, director of the vascular physiology and thrombosis research laboratory at the Burns and Allen Research Institute at Cedars Sinai Medical Center in Los Angeles.

Among the 1,374 patients enrolled in the STOP-HF (Screening to Prevent Heart Failure) trial, annual BNP measurement found 498 (36%) with a BNP level that rose above 50 pg/mL in at least one annual test. This included 235 patients randomized to the control arm and 263 randomized to the intervention group. The overall age of patients in the study averaged 65 years, but the age of those with elevated BNP averaged closer to 70 years.

During average follow-up of just over 4 years, patients referred to the cardiology program had 25 cases (10%) of heart failure or asymptomatic left ventricular dysfunction, compared with 44 cases (19%) in the control arm, a 54% odds ratio reduction that was statistically significant for the study’s primary endpoint. For the entire study group of 1,374 randomized patients, participation in the group eligible for referred care cut the primary endpoint by a relative 41%, compared with the controls, a statistically significant difference.

Mitchel L. Zoler/IMNG Medical Media

A secondary efficacy analysis that tallied the combined rate of incident heart failure, arrhythmia, myocardial infarction, unstable angina, cerebrovascular events, peripheral thrombosis, or pulmonary embolism found 51 events (7%) in the entire intervention group compared with 71 events (10%) in the control group, a 46% odds rate reduction that was statistically significant.

A study limitation was the large percentage of patients in both arms either lost to follow-up, 10%; or who withdrew their consent to participate, another 16%. "It challenges interpretation of the results," commented Dr. Kaul.

But Dr. McDonald and his associates were convinced by their findings.

"We believe the results are conclusive enough to roll this out as a clinical program," he said in an interview. "We are now extending this to another region of Ireland, and we will try to get this disseminated nationally."

He also foresees additional refinements to the program, possibly identifying other risk markers that can compliment BNP and further focus intervention.

"We have shown benefit, but a question is the cost of getting that benefit. BNP is clearly a step up from where we were, but that doesn’t mean we are as good as we could make it."

Dr. McDonald said that he had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LOS ANGELES – Some patients with a total artificial heart can safely go home with the use of a small portable driver while awaiting heart transplantation, according to data from the first U.S. patient cohort in whom this was attempted.

Investigators assessed outcomes in 13 total artificial heart recipients who were stable enough clinically to be transitioned from the usual driver to SynCardia Systems’ investigational portable driver, the Freedom Driver System. The driver weighs 14 pounds and allows several hours of untethered activity.

Eight of the patients were able to go home for an average of 5.5 months, lead investigator Dr. Vigneshwar Kasirajan reported at the annual meeting of the Society of Thoracic Surgeons.

They had a low rate of major bleeding and no major infections. There were roughly five device malfunctions per patient-year, but in all cases, patients were able to switch to a backup driver uneventfully.

 Twelve of the 13 total patients ultimately underwent transplantation, for a transplantation rate of 92%.

"The Freedom driver is effective in supporting circulation with a total artificial heart. Discharge home is safe and feasible," commented Dr. Kasirajan, who is director of heart transplantation, heart-lung transplantation, and mechanical circulatory support at Virginia Commonwealth University in Richmond.

"Further data on the completion of this study will help to demonstrate the efficacy and safety of the driver. In addition, important data on exercise capacity and quality of life will be valuable in finally moving the artificial heart technology to more widespread use," he said.

Session comoderator Dr. Todd M. Dewey, a cardiothoracic surgeon with Medical City Specialists in Dallas, noted, "The majority of patients on axial-flow left ventricular assist devices are discharged home. What percentage of total artificial heart patients do you think will ultimately leave the hospital?"

"We are close to 80% of our patients going home right now, at least in high-volume institutions," Dr. Kasirajan replied. Two patients have been at home for more than 2 years without readmissions related to the device, he added.

A pivotal study previously showed that the total artificial heart can be used as a bridge to transplantation in patients with irreversible biventricular failure (N. Engl. J. Med. 2004;351:859-67).

"Unfortunately, ... the widespread use of this technology is limited because of the inability to discharge these patients home, and that relates to the fact that the circulatory support system console has to be powered by compressed air either from the hospital or via a cylinder," Dr. Kasirajan explained.

However, once patients are stable, the driver settings need little adjustment, which spurred development of the portable driver. "The driver has two batteries that allow up to 3 hours of untethered activity. These can be charged in place using an alternating current output or car charger," he said.

The ongoing study of the driver will enroll up to 60 patients from 30 international sites. Patients are required to be wait-listed for heart transplantation and receive a total artificial heart, and to be clinically stable on the circulatory support system, with a cardiac index of at least 2.2 L/min/m². They are then switched to the portable driver with the intent of discharge from the hospital.

Dr. Kasirajan reported results for the first 13 patients enrolled from four U.S. sites. Overall, 5 of the patients remained in the hospital (because of medical reasons, discharge logistics, or personal preference), whereas 8 went home with the driver. The median duration out of the hospital in the latter group was 162 days (range, 39-437 days).

The 13 patients had maintenance of cardiac function, with a cardiac index averaging 3.3 L/min/m², and their laboratory values remained stable between baseline and 90 days. "Particularly, there was no evidence of hemolysis that was worse than at the beginning," he noted. "Increasing albumin levels reflect the increasing nutritional status in these patients."

The in-hospital group had a very similar rate of adverse events relative to an earlier comparison cohort of stable patients with a total artificial heart followed as part of postmarket surveillance, according to Dr. Kasirajan.

Within the study population, the out-of-hospital and in-hospital groups had similar rates of major bleeding (1.1 vs. 1.4 events per patient-year). The former had a lower rate of major infection (0 vs. 2.8 events per patient-year) but higher rates of device malfunction (4.6 vs. 0 events per patient-year) and hemolysis (2.3 vs. 0 events per patient-year).

The five device malfunctions in the out-of-hospital group were due to a Valsalva maneuver, a faulty sensor, hypertension, a kink in the driveline while a patient was getting into a car, and dropping of the driver while showering.

"All these patients remained stable and had no changes in cardiac output," Dr. Kasirajan pointed out. "They were able to switch to the backup driver as educated, and returned to the hospital."

Valsalva maneuvers can cause a sudden transient rise in intrathoracic pressure that a device sensor interprets as outside the set parameters, he explained; the software has since been modified to allow for these changes.

"The importance of hypertension management is critical," he commented. "The pump tolerates blood pressures at high levels for brief periods of time; however, prolonged hypertension leads to a decrease in left heart cardiac output and pulmonary edema."

The cases of hemolysis were due to transient rises in plasma free hemoglobin as a result of hemothorax and hydralazine-induced hemolytic anemia.

Only a single patient, in the out-of-hospital group, died before transplantation. This patient was stable on the driver for 437 days, but experienced a fall with a spinal cord hematoma, and developed fatal complications.

Dr. Kasirajan disclosed that he is a consultant to SynCardia Systems.

LOS ANGELES – Some patients with a total artificial heart can safely go home with the use of a small portable driver while awaiting heart transplantation, according to data from the first U.S. patient cohort in whom this was attempted.

Investigators assessed outcomes in 13 total artificial heart recipients who were stable enough clinically to be transitioned from the usual driver to SynCardia Systems’ investigational portable driver, the Freedom Driver System. The driver weighs 14 pounds and allows several hours of untethered activity.

Eight of the patients were able to go home for an average of 5.5 months, lead investigator Dr. Vigneshwar Kasirajan reported at the annual meeting of the Society of Thoracic Surgeons.

They had a low rate of major bleeding and no major infections. There were roughly five device malfunctions per patient-year, but in all cases, patients were able to switch to a backup driver uneventfully.

 Twelve of the 13 total patients ultimately underwent transplantation, for a transplantation rate of 92%.

"The Freedom driver is effective in supporting circulation with a total artificial heart. Discharge home is safe and feasible," commented Dr. Kasirajan, who is director of heart transplantation, heart-lung transplantation, and mechanical circulatory support at Virginia Commonwealth University in Richmond.

"Further data on the completion of this study will help to demonstrate the efficacy and safety of the driver. In addition, important data on exercise capacity and quality of life will be valuable in finally moving the artificial heart technology to more widespread use," he said.

Session comoderator Dr. Todd M. Dewey, a cardiothoracic surgeon with Medical City Specialists in Dallas, noted, "The majority of patients on axial-flow left ventricular assist devices are discharged home. What percentage of total artificial heart patients do you think will ultimately leave the hospital?"

"We are close to 80% of our patients going home right now, at least in high-volume institutions," Dr. Kasirajan replied. Two patients have been at home for more than 2 years without readmissions related to the device, he added.

A pivotal study previously showed that the total artificial heart can be used as a bridge to transplantation in patients with irreversible biventricular failure (N. Engl. J. Med. 2004;351:859-67).

"Unfortunately, ... the widespread use of this technology is limited because of the inability to discharge these patients home, and that relates to the fact that the circulatory support system console has to be powered by compressed air either from the hospital or via a cylinder," Dr. Kasirajan explained.

However, once patients are stable, the driver settings need little adjustment, which spurred development of the portable driver. "The driver has two batteries that allow up to 3 hours of untethered activity. These can be charged in place using an alternating current output or car charger," he said.

The ongoing study of the driver will enroll up to 60 patients from 30 international sites. Patients are required to be wait-listed for heart transplantation and receive a total artificial heart, and to be clinically stable on the circulatory support system, with a cardiac index of at least 2.2 L/min/m². They are then switched to the portable driver with the intent of discharge from the hospital.

Dr. Kasirajan reported results for the first 13 patients enrolled from four U.S. sites. Overall, 5 of the patients remained in the hospital (because of medical reasons, discharge logistics, or personal preference), whereas 8 went home with the driver. The median duration out of the hospital in the latter group was 162 days (range, 39-437 days).

The 13 patients had maintenance of cardiac function, with a cardiac index averaging 3.3 L/min/m², and their laboratory values remained stable between baseline and 90 days. "Particularly, there was no evidence of hemolysis that was worse than at the beginning," he noted. "Increasing albumin levels reflect the increasing nutritional status in these patients."

The in-hospital group had a very similar rate of adverse events relative to an earlier comparison cohort of stable patients with a total artificial heart followed as part of postmarket surveillance, according to Dr. Kasirajan.

Within the study population, the out-of-hospital and in-hospital groups had similar rates of major bleeding (1.1 vs. 1.4 events per patient-year). The former had a lower rate of major infection (0 vs. 2.8 events per patient-year) but higher rates of device malfunction (4.6 vs. 0 events per patient-year) and hemolysis (2.3 vs. 0 events per patient-year).

The five device malfunctions in the out-of-hospital group were due to a Valsalva maneuver, a faulty sensor, hypertension, a kink in the driveline while a patient was getting into a car, and dropping of the driver while showering.

"All these patients remained stable and had no changes in cardiac output," Dr. Kasirajan pointed out. "They were able to switch to the backup driver as educated, and returned to the hospital."

Valsalva maneuvers can cause a sudden transient rise in intrathoracic pressure that a device sensor interprets as outside the set parameters, he explained; the software has since been modified to allow for these changes.

"The importance of hypertension management is critical," he commented. "The pump tolerates blood pressures at high levels for brief periods of time; however, prolonged hypertension leads to a decrease in left heart cardiac output and pulmonary edema."

The cases of hemolysis were due to transient rises in plasma free hemoglobin as a result of hemothorax and hydralazine-induced hemolytic anemia.

Only a single patient, in the out-of-hospital group, died before transplantation. This patient was stable on the driver for 437 days, but experienced a fall with a spinal cord hematoma, and developed fatal complications.

Dr. Kasirajan disclosed that he is a consultant to SynCardia Systems.

LOS ANGELES – Some patients with a total artificial heart can safely go home with the use of a small portable driver while awaiting heart transplantation, according to data from the first U.S. patient cohort in whom this was attempted.

Investigators assessed outcomes in 13 total artificial heart recipients who were stable enough clinically to be transitioned from the usual driver to SynCardia Systems’ investigational portable driver, the Freedom Driver System. The driver weighs 14 pounds and allows several hours of untethered activity.

Eight of the patients were able to go home for an average of 5.5 months, lead investigator Dr. Vigneshwar Kasirajan reported at the annual meeting of the Society of Thoracic Surgeons.

They had a low rate of major bleeding and no major infections. There were roughly five device malfunctions per patient-year, but in all cases, patients were able to switch to a backup driver uneventfully.

 Twelve of the 13 total patients ultimately underwent transplantation, for a transplantation rate of 92%.

"The Freedom driver is effective in supporting circulation with a total artificial heart. Discharge home is safe and feasible," commented Dr. Kasirajan, who is director of heart transplantation, heart-lung transplantation, and mechanical circulatory support at Virginia Commonwealth University in Richmond.

"Further data on the completion of this study will help to demonstrate the efficacy and safety of the driver. In addition, important data on exercise capacity and quality of life will be valuable in finally moving the artificial heart technology to more widespread use," he said.

Session comoderator Dr. Todd M. Dewey, a cardiothoracic surgeon with Medical City Specialists in Dallas, noted, "The majority of patients on axial-flow left ventricular assist devices are discharged home. What percentage of total artificial heart patients do you think will ultimately leave the hospital?"

"We are close to 80% of our patients going home right now, at least in high-volume institutions," Dr. Kasirajan replied. Two patients have been at home for more than 2 years without readmissions related to the device, he added.

A pivotal study previously showed that the total artificial heart can be used as a bridge to transplantation in patients with irreversible biventricular failure (N. Engl. J. Med. 2004;351:859-67).

"Unfortunately, ... the widespread use of this technology is limited because of the inability to discharge these patients home, and that relates to the fact that the circulatory support system console has to be powered by compressed air either from the hospital or via a cylinder," Dr. Kasirajan explained.

However, once patients are stable, the driver settings need little adjustment, which spurred development of the portable driver. "The driver has two batteries that allow up to 3 hours of untethered activity. These can be charged in place using an alternating current output or car charger," he said.

The ongoing study of the driver will enroll up to 60 patients from 30 international sites. Patients are required to be wait-listed for heart transplantation and receive a total artificial heart, and to be clinically stable on the circulatory support system, with a cardiac index of at least 2.2 L/min/m². They are then switched to the portable driver with the intent of discharge from the hospital.

Dr. Kasirajan reported results for the first 13 patients enrolled from four U.S. sites. Overall, 5 of the patients remained in the hospital (because of medical reasons, discharge logistics, or personal preference), whereas 8 went home with the driver. The median duration out of the hospital in the latter group was 162 days (range, 39-437 days).

The 13 patients had maintenance of cardiac function, with a cardiac index averaging 3.3 L/min/m², and their laboratory values remained stable between baseline and 90 days. "Particularly, there was no evidence of hemolysis that was worse than at the beginning," he noted. "Increasing albumin levels reflect the increasing nutritional status in these patients."

The in-hospital group had a very similar rate of adverse events relative to an earlier comparison cohort of stable patients with a total artificial heart followed as part of postmarket surveillance, according to Dr. Kasirajan.

Within the study population, the out-of-hospital and in-hospital groups had similar rates of major bleeding (1.1 vs. 1.4 events per patient-year). The former had a lower rate of major infection (0 vs. 2.8 events per patient-year) but higher rates of device malfunction (4.6 vs. 0 events per patient-year) and hemolysis (2.3 vs. 0 events per patient-year).

The five device malfunctions in the out-of-hospital group were due to a Valsalva maneuver, a faulty sensor, hypertension, a kink in the driveline while a patient was getting into a car, and dropping of the driver while showering.

"All these patients remained stable and had no changes in cardiac output," Dr. Kasirajan pointed out. "They were able to switch to the backup driver as educated, and returned to the hospital."

Valsalva maneuvers can cause a sudden transient rise in intrathoracic pressure that a device sensor interprets as outside the set parameters, he explained; the software has since been modified to allow for these changes.

"The importance of hypertension management is critical," he commented. "The pump tolerates blood pressures at high levels for brief periods of time; however, prolonged hypertension leads to a decrease in left heart cardiac output and pulmonary edema."

The cases of hemolysis were due to transient rises in plasma free hemoglobin as a result of hemothorax and hydralazine-induced hemolytic anemia.

Only a single patient, in the out-of-hospital group, died before transplantation. This patient was stable on the driver for 437 days, but experienced a fall with a spinal cord hematoma, and developed fatal complications.

Dr. Kasirajan disclosed that he is a consultant to SynCardia Systems.

GAITHERSBURG, MD – An expert panel narrowly voted in favor of recommending Food and Drug Administration approval of a novel, percutaneously implanted device that repairs the mitral valve for use in selected patients with significant symptomatic mitral regurgitation who are poor surgical candidates.

At a meeting on March 20, the FDA’s Circulatory Systems Devices panel, it voted 5-3 that the benefits of the MitraClip Delivery System outweighed the risks for patients who met the criteria specified in the indication under review: "percutaneous reduction of significant symptomatic mitral regurgitation [moderate to severe (3+)MR] in patients who have been determined by a cardiac surgeon to be too high risk for open mitral valve surgery and in whom existing co-morbidities would not preclude the expected benefit from correction of the mitral regurgitation."

The panel was more comfortable with the safety data, unanimously voting that there was "reasonable assurance" that the device was safe for patients who met the criteria in the indication.

Largely because of limitations of the studies submitted by manufacturer Abbott Vascular – which included combining nonpivotal data from two high-risk patient registries – the panel was less confident with the efficacy data, voting 5-4 that there was not reasonable assurance that the device was effective. (The extra vote was the panel chair, who votes in case of a tie, and he voted no.)

The panelists generally agreed with the FDA’s conclusions that there were numerous problems with the data – the basis of the FDA’s conclusion that the device should not be approved at this time – but they said that they had a sense there were patients who could benefit from treatment.

Dr. Craig Selzman, a cardiothoracic surgeon at the University of Utah, Salt Lake City, voted in favor of approval "with trepidation" because he believed the benefit-risk ratio was likely favorable, based on the safety profile and the apparent benefit. He stressed, however, that the device should be limited to "truly inoperable patients" and warned about "indication creep," when a device is rapidly used for treating patients outside the approved indication once it is marketed. He also recommended that the patient should be on optimal medical treatment and that an experienced mitral valve surgeon should identify which patients are candidates for treatment.

Also voting in favor of approval, Dr. George Vetrovec, professor of medicine and director of the adult cardiac catheterization laboratory at the Medical College of Virginia, Richmond, like several others, cited the improvements in New York Heart Association class in those treated with the device, "which got so much better it couldn’t just be happenstance. ... It seemed to me that had to be real and overall risks seemed to be reasonable for a very selected, limited population."

Those voting against approval said that treatment with the device appeared to be potentially beneficial but that it was difficult to identify which patients would benefit from treatment. Therefore, a randomized controlled trial was needed before approval.

The MitraClip system includes a delivery catheter and the MitraClip device, a mechanical clip designed to reduce regurgitation by clipping together the leaflets of the mitral valve.

In its application, Abbott combined two studies of nonpivotal data – a single-arm study of 78 high-risk patients that was an adjunct to EVEREST II (a randomized controlled study of patients with mitral regurgitation who were surgical candidates that did not find a benefit of MitraClip over surgery) and another registry of 273 high-risk patients (REALISM). The 351 patients had functional or degenerative MR, their mean age was 76 years, mean ejection fraction was 48%, 85% were NYHA functional class III/IV, and their mean predicted surgical mortality risk was 18%.

Implantation was successful in about 95% of patients, and the major effectiveness end point, change in left ventricular size from baseline to 1 year, significantly improved, with about a 10% reduction in LV volumes and LV dimensions. Other changes included improvements in NYHA class (including a two-class improvement in 36% of patients at 1 year) and significant improvement in a quality-of-life questionnaire. There were also reductions in heart failure hospitalization rates in the year after implantation, compared with the year before; the mean hospital stay was about 3 days. The primary safety end point, 30-day mortality, was 4.8%, which was lower than the mean predicted mortality risk of 18%, according to the company. Three of the 17 deaths within the first 30 days were device related.

The company also compared mortality in a Duke University cardiovascular database of high-surgical-risk patients who were treated medically (31% at 1 year), with mortality in a matched cohort of 211 MitraClip patients in the registry studies (24%), which the company concluded indicated that there was no increased mortality of the procedure compared with the natural history of the disease.

The FDA reviewers concluded that the device could not be approved, citing multiple problems with the registry data, which were not intended to be used as pivotal data, were difficult to interpret, and could only be considered "hypothesis-generating" at this point.

Abbott recently started two studies – one in the United States involving patients with symptomatic functional mitral regurgitation who are not good surgical candidates, the other a postmarketing study in Europe of patients with severe heart failure – and has plans for postmarketing studies in the United States, including 5-year follow-up of the patients in the combined high-risk registry trials, and a national MitraClip patient registry.

The device received the equivalent of approval in the European Union in 2008 and is marketed in about 30 countries, according to Abbott.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, and at this meeting, two such waivers were granted to the panel chair, Dr. Jeffrey Borer, professor of medicine at the State University of New York, Downstate Medical Center in Brooklyn, and Dr. Vetrovec. Dr. Borer also is an adjunct professor at Cornell University, a clinical site of a MitraClip study, but he is not one of the investigators. Dr. Vetrovec reported stockholdings in Abbott and in two firms that make competing products.

emechcatie@frontlinemedcom.com

GAITHERSBURG, MD – An expert panel narrowly voted in favor of recommending Food and Drug Administration approval of a novel, percutaneously implanted device that repairs the mitral valve for use in selected patients with significant symptomatic mitral regurgitation who are poor surgical candidates.

At a meeting on March 20, the FDA’s Circulatory Systems Devices panel, it voted 5-3 that the benefits of the MitraClip Delivery System outweighed the risks for patients who met the criteria specified in the indication under review: "percutaneous reduction of significant symptomatic mitral regurgitation [moderate to severe (3+)MR] in patients who have been determined by a cardiac surgeon to be too high risk for open mitral valve surgery and in whom existing co-morbidities would not preclude the expected benefit from correction of the mitral regurgitation."

The panel was more comfortable with the safety data, unanimously voting that there was "reasonable assurance" that the device was safe for patients who met the criteria in the indication.

Largely because of limitations of the studies submitted by manufacturer Abbott Vascular – which included combining nonpivotal data from two high-risk patient registries – the panel was less confident with the efficacy data, voting 5-4 that there was not reasonable assurance that the device was effective. (The extra vote was the panel chair, who votes in case of a tie, and he voted no.)

The panelists generally agreed with the FDA’s conclusions that there were numerous problems with the data – the basis of the FDA’s conclusion that the device should not be approved at this time – but they said that they had a sense there were patients who could benefit from treatment.

Dr. Craig Selzman, a cardiothoracic surgeon at the University of Utah, Salt Lake City, voted in favor of approval "with trepidation" because he believed the benefit-risk ratio was likely favorable, based on the safety profile and the apparent benefit. He stressed, however, that the device should be limited to "truly inoperable patients" and warned about "indication creep," when a device is rapidly used for treating patients outside the approved indication once it is marketed. He also recommended that the patient should be on optimal medical treatment and that an experienced mitral valve surgeon should identify which patients are candidates for treatment.

Also voting in favor of approval, Dr. George Vetrovec, professor of medicine and director of the adult cardiac catheterization laboratory at the Medical College of Virginia, Richmond, like several others, cited the improvements in New York Heart Association class in those treated with the device, "which got so much better it couldn’t just be happenstance. ... It seemed to me that had to be real and overall risks seemed to be reasonable for a very selected, limited population."

Those voting against approval said that treatment with the device appeared to be potentially beneficial but that it was difficult to identify which patients would benefit from treatment. Therefore, a randomized controlled trial was needed before approval.

The MitraClip system includes a delivery catheter and the MitraClip device, a mechanical clip designed to reduce regurgitation by clipping together the leaflets of the mitral valve.

In its application, Abbott combined two studies of nonpivotal data – a single-arm study of 78 high-risk patients that was an adjunct to EVEREST II (a randomized controlled study of patients with mitral regurgitation who were surgical candidates that did not find a benefit of MitraClip over surgery) and another registry of 273 high-risk patients (REALISM). The 351 patients had functional or degenerative MR, their mean age was 76 years, mean ejection fraction was 48%, 85% were NYHA functional class III/IV, and their mean predicted surgical mortality risk was 18%.

Implantation was successful in about 95% of patients, and the major effectiveness end point, change in left ventricular size from baseline to 1 year, significantly improved, with about a 10% reduction in LV volumes and LV dimensions. Other changes included improvements in NYHA class (including a two-class improvement in 36% of patients at 1 year) and significant improvement in a quality-of-life questionnaire. There were also reductions in heart failure hospitalization rates in the year after implantation, compared with the year before; the mean hospital stay was about 3 days. The primary safety end point, 30-day mortality, was 4.8%, which was lower than the mean predicted mortality risk of 18%, according to the company. Three of the 17 deaths within the first 30 days were device related.

The company also compared mortality in a Duke University cardiovascular database of high-surgical-risk patients who were treated medically (31% at 1 year), with mortality in a matched cohort of 211 MitraClip patients in the registry studies (24%), which the company concluded indicated that there was no increased mortality of the procedure compared with the natural history of the disease.

The FDA reviewers concluded that the device could not be approved, citing multiple problems with the registry data, which were not intended to be used as pivotal data, were difficult to interpret, and could only be considered "hypothesis-generating" at this point.

Abbott recently started two studies – one in the United States involving patients with symptomatic functional mitral regurgitation who are not good surgical candidates, the other a postmarketing study in Europe of patients with severe heart failure – and has plans for postmarketing studies in the United States, including 5-year follow-up of the patients in the combined high-risk registry trials, and a national MitraClip patient registry.

The device received the equivalent of approval in the European Union in 2008 and is marketed in about 30 countries, according to Abbott.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, and at this meeting, two such waivers were granted to the panel chair, Dr. Jeffrey Borer, professor of medicine at the State University of New York, Downstate Medical Center in Brooklyn, and Dr. Vetrovec. Dr. Borer also is an adjunct professor at Cornell University, a clinical site of a MitraClip study, but he is not one of the investigators. Dr. Vetrovec reported stockholdings in Abbott and in two firms that make competing products.

emechcatie@frontlinemedcom.com

GAITHERSBURG, MD – An expert panel narrowly voted in favor of recommending Food and Drug Administration approval of a novel, percutaneously implanted device that repairs the mitral valve for use in selected patients with significant symptomatic mitral regurgitation who are poor surgical candidates.

At a meeting on March 20, the FDA’s Circulatory Systems Devices panel, it voted 5-3 that the benefits of the MitraClip Delivery System outweighed the risks for patients who met the criteria specified in the indication under review: "percutaneous reduction of significant symptomatic mitral regurgitation [moderate to severe (3+)MR] in patients who have been determined by a cardiac surgeon to be too high risk for open mitral valve surgery and in whom existing co-morbidities would not preclude the expected benefit from correction of the mitral regurgitation."

The panel was more comfortable with the safety data, unanimously voting that there was "reasonable assurance" that the device was safe for patients who met the criteria in the indication.

Largely because of limitations of the studies submitted by manufacturer Abbott Vascular – which included combining nonpivotal data from two high-risk patient registries – the panel was less confident with the efficacy data, voting 5-4 that there was not reasonable assurance that the device was effective. (The extra vote was the panel chair, who votes in case of a tie, and he voted no.)

The panelists generally agreed with the FDA’s conclusions that there were numerous problems with the data – the basis of the FDA’s conclusion that the device should not be approved at this time – but they said that they had a sense there were patients who could benefit from treatment.

Dr. Craig Selzman, a cardiothoracic surgeon at the University of Utah, Salt Lake City, voted in favor of approval "with trepidation" because he believed the benefit-risk ratio was likely favorable, based on the safety profile and the apparent benefit. He stressed, however, that the device should be limited to "truly inoperable patients" and warned about "indication creep," when a device is rapidly used for treating patients outside the approved indication once it is marketed. He also recommended that the patient should be on optimal medical treatment and that an experienced mitral valve surgeon should identify which patients are candidates for treatment.

Also voting in favor of approval, Dr. George Vetrovec, professor of medicine and director of the adult cardiac catheterization laboratory at the Medical College of Virginia, Richmond, like several others, cited the improvements in New York Heart Association class in those treated with the device, "which got so much better it couldn’t just be happenstance. ... It seemed to me that had to be real and overall risks seemed to be reasonable for a very selected, limited population."

Those voting against approval said that treatment with the device appeared to be potentially beneficial but that it was difficult to identify which patients would benefit from treatment. Therefore, a randomized controlled trial was needed before approval.

The MitraClip system includes a delivery catheter and the MitraClip device, a mechanical clip designed to reduce regurgitation by clipping together the leaflets of the mitral valve.

In its application, Abbott combined two studies of nonpivotal data – a single-arm study of 78 high-risk patients that was an adjunct to EVEREST II (a randomized controlled study of patients with mitral regurgitation who were surgical candidates that did not find a benefit of MitraClip over surgery) and another registry of 273 high-risk patients (REALISM). The 351 patients had functional or degenerative MR, their mean age was 76 years, mean ejection fraction was 48%, 85% were NYHA functional class III/IV, and their mean predicted surgical mortality risk was 18%.

Implantation was successful in about 95% of patients, and the major effectiveness end point, change in left ventricular size from baseline to 1 year, significantly improved, with about a 10% reduction in LV volumes and LV dimensions. Other changes included improvements in NYHA class (including a two-class improvement in 36% of patients at 1 year) and significant improvement in a quality-of-life questionnaire. There were also reductions in heart failure hospitalization rates in the year after implantation, compared with the year before; the mean hospital stay was about 3 days. The primary safety end point, 30-day mortality, was 4.8%, which was lower than the mean predicted mortality risk of 18%, according to the company. Three of the 17 deaths within the first 30 days were device related.

The company also compared mortality in a Duke University cardiovascular database of high-surgical-risk patients who were treated medically (31% at 1 year), with mortality in a matched cohort of 211 MitraClip patients in the registry studies (24%), which the company concluded indicated that there was no increased mortality of the procedure compared with the natural history of the disease.

The FDA reviewers concluded that the device could not be approved, citing multiple problems with the registry data, which were not intended to be used as pivotal data, were difficult to interpret, and could only be considered "hypothesis-generating" at this point.

Abbott recently started two studies – one in the United States involving patients with symptomatic functional mitral regurgitation who are not good surgical candidates, the other a postmarketing study in Europe of patients with severe heart failure – and has plans for postmarketing studies in the United States, including 5-year follow-up of the patients in the combined high-risk registry trials, and a national MitraClip patient registry.

The device received the equivalent of approval in the European Union in 2008 and is marketed in about 30 countries, according to Abbott.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, and at this meeting, two such waivers were granted to the panel chair, Dr. Jeffrey Borer, professor of medicine at the State University of New York, Downstate Medical Center in Brooklyn, and Dr. Vetrovec. Dr. Borer also is an adjunct professor at Cornell University, a clinical site of a MitraClip study, but he is not one of the investigators. Dr. Vetrovec reported stockholdings in Abbott and in two firms that make competing products.

emechcatie@frontlinemedcom.com

SAN FRANCISCO – Sildenafil was no better than placebo for improving exercise capacity or clinical status in patients with heart failure and preserved ejection fraction, based on the results of a 24-week randomized trial published online in JAMA Mar. 11 and presented simultaneously at the annual meeting of the American College of Cardiology.

Sildenafil (Viagra), a phosphodiesterase-5 inhibitor, was shown beneficial in a previous single-center study of patients with heart failure and preserved ejection fraction (HFPEF). In the randomized trial, however, sildenafil had no significant effect "on maximal or submaximal exercise capacity, clinical status, quality of life, left ventricular remodeling, diastolic function parameters, or pulmonary artery systolic pressure," wrote lead investigator Dr. Margaret Redfield, professor of medicine at the Mayo Clinic in Rochester, Minn., and her colleagues (JAMA 2013 Mar. 11 [doi:10.1001/jama.2013.2024]).

Further, sildenafil appeared to be associated with poorer outcomes as "renal function worsened more and NT-proBNP [N-terminal fragment of the precursor to brain-type natriuretic peptide], endothelin-1, and uric acid levels increased more in patients treated with sildenafil," the researchers wrote. There was a trend, though not significant, for more patients in the sildenafil group to withdraw consent, die, or be too ill to perform the cardiopulmonary exercise test.

The researchers randomized 113 HFPEF patients to 20 mg of sildenafil three times daily for 12 weeks, followed by 60 mg three times daily for 12 weeks; 103 others were randomized to placebo in the multicenter trial.

At week 24, there were no statistically significant differences between the placebo and sildenafil groups in median changes in peak oxygen consumption (P = 0.90); median clinical status rank score—a composite of quality of life changes and times to death or hospitalization (P = 0.85); or changes in 6-minute walk distance (placebo 15.0 m, sildenafil 5.0 m; P = 0.92).

The median age in the trial was 69 years, 48% of the patients were women, and patients were under treatment for diabetes, atrial fibrillation, kidney disease, and other comorbidities. They were stable at baseline with ejection fractions equal to or greater than 50%, but had reduced exercise capacity, median peak oxygen consumption, and 6-minute walk distances. Their left atrial volumes and other measurements were consistent with chronically elevated left ventricular filling pressures.

A higher incidence of vascular adverse events was seen in the sildenafil group and included headache, flushing, and hypotension. Arterial elasticity and systemic vascular resistance tended to decrease more in sildenafil patients, but there were no significant changes in mean arterial pressure between the two groups.

Cardiac, respiratory, or other serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). Three people died in the sildenafil arm, but none in the placebo arm.

The "modest but statistically significant worsening of renal function" in sildenafil patients has not been reported before in studies of pulmonary arterial hypertension and erectile dysfunction, the investigators noted.

A previous single-center study found a benefit for sildenafil over placebo in HFPEF for left ventricular diastolic function, right ventricular systolic function, and left ventricular hypertrophy; the effect on exercise capacity was not tested (Circulation 2011;124:164-74).

"In that study, patients with HFPEF had fewer comorbidities and significantly higher blood pressure, left ventricular mass, and pulmonary artery systolic pressure ... [plus] catheterization-documented pulmonary arterial hypertension, profound right ventricular systolic dysfunction, and right ventricular failure. [The] profile [was] somewhat atypical for HFPEF cohorts," the investigators wrote.

"It may be that the primary therapeutic effects of PDE-5 inhibitors in heart failure involve the drugs’ ability to dilate the pulmonary vascular bed, enhance right ventricular contractility, and reduce ventricular interdependence, and that pulmonary arterial hypertension and right ventricular failure must be significant in order to observe clinical benefit in HFPEF," they wrote.

"Although left ventricular hypertrophy was common in participants in this study, it was far less severe than among participants in the [previous] study. ... Conceivably, activation of PDE-5 or of cyclic guanosine monophosphate–sensitive downstream pathways in the left ventricle or other organs may occur only in heart failure associated with advanced left ventricular remodeling," they wrote.

The study was funded by the National Institutes of Health. Pfizer donated the sildenafil and matched placebo. The investigators reported commercial relationships with many companies, including Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche.

SAN FRANCISCO – Sildenafil was no better than placebo for improving exercise capacity or clinical status in patients with heart failure and preserved ejection fraction, based on the results of a 24-week randomized trial published online in JAMA Mar. 11 and presented simultaneously at the annual meeting of the American College of Cardiology.

Sildenafil (Viagra), a phosphodiesterase-5 inhibitor, was shown beneficial in a previous single-center study of patients with heart failure and preserved ejection fraction (HFPEF). In the randomized trial, however, sildenafil had no significant effect "on maximal or submaximal exercise capacity, clinical status, quality of life, left ventricular remodeling, diastolic function parameters, or pulmonary artery systolic pressure," wrote lead investigator Dr. Margaret Redfield, professor of medicine at the Mayo Clinic in Rochester, Minn., and her colleagues (JAMA 2013 Mar. 11 [doi:10.1001/jama.2013.2024]).

Further, sildenafil appeared to be associated with poorer outcomes as "renal function worsened more and NT-proBNP [N-terminal fragment of the precursor to brain-type natriuretic peptide], endothelin-1, and uric acid levels increased more in patients treated with sildenafil," the researchers wrote. There was a trend, though not significant, for more patients in the sildenafil group to withdraw consent, die, or be too ill to perform the cardiopulmonary exercise test.

The researchers randomized 113 HFPEF patients to 20 mg of sildenafil three times daily for 12 weeks, followed by 60 mg three times daily for 12 weeks; 103 others were randomized to placebo in the multicenter trial.

At week 24, there were no statistically significant differences between the placebo and sildenafil groups in median changes in peak oxygen consumption (P = 0.90); median clinical status rank score—a composite of quality of life changes and times to death or hospitalization (P = 0.85); or changes in 6-minute walk distance (placebo 15.0 m, sildenafil 5.0 m; P = 0.92).

The median age in the trial was 69 years, 48% of the patients were women, and patients were under treatment for diabetes, atrial fibrillation, kidney disease, and other comorbidities. They were stable at baseline with ejection fractions equal to or greater than 50%, but had reduced exercise capacity, median peak oxygen consumption, and 6-minute walk distances. Their left atrial volumes and other measurements were consistent with chronically elevated left ventricular filling pressures.

A higher incidence of vascular adverse events was seen in the sildenafil group and included headache, flushing, and hypotension. Arterial elasticity and systemic vascular resistance tended to decrease more in sildenafil patients, but there were no significant changes in mean arterial pressure between the two groups.

Cardiac, respiratory, or other serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). Three people died in the sildenafil arm, but none in the placebo arm.

The "modest but statistically significant worsening of renal function" in sildenafil patients has not been reported before in studies of pulmonary arterial hypertension and erectile dysfunction, the investigators noted.

A previous single-center study found a benefit for sildenafil over placebo in HFPEF for left ventricular diastolic function, right ventricular systolic function, and left ventricular hypertrophy; the effect on exercise capacity was not tested (Circulation 2011;124:164-74).

"In that study, patients with HFPEF had fewer comorbidities and significantly higher blood pressure, left ventricular mass, and pulmonary artery systolic pressure ... [plus] catheterization-documented pulmonary arterial hypertension, profound right ventricular systolic dysfunction, and right ventricular failure. [The] profile [was] somewhat atypical for HFPEF cohorts," the investigators wrote.

"It may be that the primary therapeutic effects of PDE-5 inhibitors in heart failure involve the drugs’ ability to dilate the pulmonary vascular bed, enhance right ventricular contractility, and reduce ventricular interdependence, and that pulmonary arterial hypertension and right ventricular failure must be significant in order to observe clinical benefit in HFPEF," they wrote.

"Although left ventricular hypertrophy was common in participants in this study, it was far less severe than among participants in the [previous] study. ... Conceivably, activation of PDE-5 or of cyclic guanosine monophosphate–sensitive downstream pathways in the left ventricle or other organs may occur only in heart failure associated with advanced left ventricular remodeling," they wrote.

The study was funded by the National Institutes of Health. Pfizer donated the sildenafil and matched placebo. The investigators reported commercial relationships with many companies, including Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche.

SAN FRANCISCO – Sildenafil was no better than placebo for improving exercise capacity or clinical status in patients with heart failure and preserved ejection fraction, based on the results of a 24-week randomized trial published online in JAMA Mar. 11 and presented simultaneously at the annual meeting of the American College of Cardiology.

Sildenafil (Viagra), a phosphodiesterase-5 inhibitor, was shown beneficial in a previous single-center study of patients with heart failure and preserved ejection fraction (HFPEF). In the randomized trial, however, sildenafil had no significant effect "on maximal or submaximal exercise capacity, clinical status, quality of life, left ventricular remodeling, diastolic function parameters, or pulmonary artery systolic pressure," wrote lead investigator Dr. Margaret Redfield, professor of medicine at the Mayo Clinic in Rochester, Minn., and her colleagues (JAMA 2013 Mar. 11 [doi:10.1001/jama.2013.2024]).

Further, sildenafil appeared to be associated with poorer outcomes as "renal function worsened more and NT-proBNP [N-terminal fragment of the precursor to brain-type natriuretic peptide], endothelin-1, and uric acid levels increased more in patients treated with sildenafil," the researchers wrote. There was a trend, though not significant, for more patients in the sildenafil group to withdraw consent, die, or be too ill to perform the cardiopulmonary exercise test.

The researchers randomized 113 HFPEF patients to 20 mg of sildenafil three times daily for 12 weeks, followed by 60 mg three times daily for 12 weeks; 103 others were randomized to placebo in the multicenter trial.

At week 24, there were no statistically significant differences between the placebo and sildenafil groups in median changes in peak oxygen consumption (P = 0.90); median clinical status rank score—a composite of quality of life changes and times to death or hospitalization (P = 0.85); or changes in 6-minute walk distance (placebo 15.0 m, sildenafil 5.0 m; P = 0.92).

The median age in the trial was 69 years, 48% of the patients were women, and patients were under treatment for diabetes, atrial fibrillation, kidney disease, and other comorbidities. They were stable at baseline with ejection fractions equal to or greater than 50%, but had reduced exercise capacity, median peak oxygen consumption, and 6-minute walk distances. Their left atrial volumes and other measurements were consistent with chronically elevated left ventricular filling pressures.

A higher incidence of vascular adverse events was seen in the sildenafil group and included headache, flushing, and hypotension. Arterial elasticity and systemic vascular resistance tended to decrease more in sildenafil patients, but there were no significant changes in mean arterial pressure between the two groups.

Cardiac, respiratory, or other serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). Three people died in the sildenafil arm, but none in the placebo arm.

The "modest but statistically significant worsening of renal function" in sildenafil patients has not been reported before in studies of pulmonary arterial hypertension and erectile dysfunction, the investigators noted.

A previous single-center study found a benefit for sildenafil over placebo in HFPEF for left ventricular diastolic function, right ventricular systolic function, and left ventricular hypertrophy; the effect on exercise capacity was not tested (Circulation 2011;124:164-74).

"In that study, patients with HFPEF had fewer comorbidities and significantly higher blood pressure, left ventricular mass, and pulmonary artery systolic pressure ... [plus] catheterization-documented pulmonary arterial hypertension, profound right ventricular systolic dysfunction, and right ventricular failure. [The] profile [was] somewhat atypical for HFPEF cohorts," the investigators wrote.

"It may be that the primary therapeutic effects of PDE-5 inhibitors in heart failure involve the drugs’ ability to dilate the pulmonary vascular bed, enhance right ventricular contractility, and reduce ventricular interdependence, and that pulmonary arterial hypertension and right ventricular failure must be significant in order to observe clinical benefit in HFPEF," they wrote.

"Although left ventricular hypertrophy was common in participants in this study, it was far less severe than among participants in the [previous] study. ... Conceivably, activation of PDE-5 or of cyclic guanosine monophosphate–sensitive downstream pathways in the left ventricle or other organs may occur only in heart failure associated with advanced left ventricular remodeling," they wrote.

The study was funded by the National Institutes of Health. Pfizer donated the sildenafil and matched placebo. The investigators reported commercial relationships with many companies, including Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche.

For patients hospitalized with heart failure, aliskiren added no significant benefit to standard therapy in preventing cardiovascular death or heart failure readmission.

The drug did, however, have some problematic effects on patients with diabetes, including significant increases in the risk of cardiovascular death and heart failure readmission at 6 months and all-cause death at 1 year.

The negative interaction between diabetes and aliskiren – an inhibitor of the angiotensin-renin-aldosterone system (RAAS) – is unclear, according to Dr. Mihai Gheorghiade and colleagues.

"[The issue] may be related to the increased risk of hypotension, hyperkalemia, and worsening renal function with the study drug," wrote Dr. Gheorghiade of Northwestern University, St. Louis, Mo., and his colleagues. The conclusions were published in the March 10 issue of JAMA and simultaneously presented at the annual meeting of the American College of Cardiology in San Francisco (JAMA 2013;309:doi10.1001/jama.2013.1954).

The randomized, placebo-controlled ASTRONAUT trial compared 6-and 12-month outcomes of aliskiren plus standard therapy to standard therapy alone in patients hospitalized with heart failure. 

The study randomized 1,639 patients; 1,615 were included in the final efficacy analysis. Patients in the investigational arm received 150 mg aliskiren daily in addition to standard treatment. Standard treatment was at the treating physician’s discretion, and could include, among others, diuretics, digoxin, ACE inhibitors, angiotensin receptor blockers, and beta-blockers. The study enrolled patients from 2009-2011; the median follow-up was 11 months

The patients were a mean of 65 years old. Their mean left ventricular ejection fraction was 28%, and mean estimated glomerular filtration rate was 67 mL/min/1.73 m³.  Nearly half (41%) had diabetes.

At admission, the mean N-terminal pro–brain natriuretic peptide (NT-proBNP) level was 4,239 pg/mL. Other drugs taken at baseline included diuretics (96%), beta-blockers (82%), ACE inhibitors or ARBs (84%), and mineralocorticoid antagonists (57%).

The primary efficacy endpoint was a combination of cardiovascular death or heart failure readmission within 6 months. This occurred in 201 (25%) of the aliskiren group and 214 (26%) of the placebo group – a nonsignificant difference. Nor were there significant differences when CV death and readmission were examined separately.

The main secondary endpoint was the composite of cardiovascular death or heart failure readmission at 12 months; again, there was no significant between-group difference (35% vs. 37%), although the events were numerically less in the aliskiren group than the control group (283 vs. 301). Parsing down the number of first cardiovascular events after treatment, the investigators did find that myocardial infarction was significantly less common in the aliskiren group (2% vs. 5%; HR 0.93; P = 0.009).

A subgroup analysis found that the drug was especially problematic for patients with diabetes. Compared to patients without the disorder who had standard treatment, diabetic patients who took aliskiren were 16% more likely to experience cardiovascular death or heart failure readmission by 6 months, and 64% more likely to experience all-cause death by 12 months.

During the treatment period, death occurred in 24% of patients with diabetes who took aliskiren, compared with 17% who took placebo – also a significant difference.

"In contrast, the rates of death among patients without a history [of diabetes] were 15% and 20% in the aliskiren and placebo groups, respectively," the authors wrote.

A number of adverse events were significantly higher in the aliskiren group, including hyperkalemia (14% vs. 13%) and severe hyperkalemia (8% vs. 5%). Hyperkalemia-related events occurred in 21% of the aliskiren group and 17% of the control group. Hypotension was also more common in the aliskiren group (17% vs. 13%). Decreased eGFR was significantly more common among those taking the study drug (11% vs. 9%), as were events potentially related to renal dysfunction (17% vs. 12%).

"The results of the ASTRONAUT study do not support the routine administration of aliskiren in addition to standard therapy, to patients hospitalized for worsening chronic heart failure," the investigators concluded, adding that the subgroup analysis was "consistent with previous reports of poor outcomes  with the use of aliskiren in patients with diabetes already taking RAAS inhibitors."

Further studies will be necessary to evaluate renin inhibiting drugs in patients with diabetes, they added.

Dr. Gheorghiade reported financial relationships with 32 pharmaceutical companies, including Novartis Pharma AG, the study sponsor.

For patients hospitalized with heart failure, aliskiren added no significant benefit to standard therapy in preventing cardiovascular death or heart failure readmission.

The drug did, however, have some problematic effects on patients with diabetes, including significant increases in the risk of cardiovascular death and heart failure readmission at 6 months and all-cause death at 1 year.

The negative interaction between diabetes and aliskiren – an inhibitor of the angiotensin-renin-aldosterone system (RAAS) – is unclear, according to Dr. Mihai Gheorghiade and colleagues.

"[The issue] may be related to the increased risk of hypotension, hyperkalemia, and worsening renal function with the study drug," wrote Dr. Gheorghiade of Northwestern University, St. Louis, Mo., and his colleagues. The conclusions were published in the March 10 issue of JAMA and simultaneously presented at the annual meeting of the American College of Cardiology in San Francisco (JAMA 2013;309:doi10.1001/jama.2013.1954).

The randomized, placebo-controlled ASTRONAUT trial compared 6-and 12-month outcomes of aliskiren plus standard therapy to standard therapy alone in patients hospitalized with heart failure. 

The study randomized 1,639 patients; 1,615 were included in the final efficacy analysis. Patients in the investigational arm received 150 mg aliskiren daily in addition to standard treatment. Standard treatment was at the treating physician’s discretion, and could include, among others, diuretics, digoxin, ACE inhibitors, angiotensin receptor blockers, and beta-blockers. The study enrolled patients from 2009-2011; the median follow-up was 11 months

The patients were a mean of 65 years old. Their mean left ventricular ejection fraction was 28%, and mean estimated glomerular filtration rate was 67 mL/min/1.73 m³.  Nearly half (41%) had diabetes.

At admission, the mean N-terminal pro–brain natriuretic peptide (NT-proBNP) level was 4,239 pg/mL. Other drugs taken at baseline included diuretics (96%), beta-blockers (82%), ACE inhibitors or ARBs (84%), and mineralocorticoid antagonists (57%).

The primary efficacy endpoint was a combination of cardiovascular death or heart failure readmission within 6 months. This occurred in 201 (25%) of the aliskiren group and 214 (26%) of the placebo group – a nonsignificant difference. Nor were there significant differences when CV death and readmission were examined separately.

The main secondary endpoint was the composite of cardiovascular death or heart failure readmission at 12 months; again, there was no significant between-group difference (35% vs. 37%), although the events were numerically less in the aliskiren group than the control group (283 vs. 301). Parsing down the number of first cardiovascular events after treatment, the investigators did find that myocardial infarction was significantly less common in the aliskiren group (2% vs. 5%; HR 0.93; P = 0.009).

A subgroup analysis found that the drug was especially problematic for patients with diabetes. Compared to patients without the disorder who had standard treatment, diabetic patients who took aliskiren were 16% more likely to experience cardiovascular death or heart failure readmission by 6 months, and 64% more likely to experience all-cause death by 12 months.

During the treatment period, death occurred in 24% of patients with diabetes who took aliskiren, compared with 17% who took placebo – also a significant difference.

"In contrast, the rates of death among patients without a history [of diabetes] were 15% and 20% in the aliskiren and placebo groups, respectively," the authors wrote.

A number of adverse events were significantly higher in the aliskiren group, including hyperkalemia (14% vs. 13%) and severe hyperkalemia (8% vs. 5%). Hyperkalemia-related events occurred in 21% of the aliskiren group and 17% of the control group. Hypotension was also more common in the aliskiren group (17% vs. 13%). Decreased eGFR was significantly more common among those taking the study drug (11% vs. 9%), as were events potentially related to renal dysfunction (17% vs. 12%).

"The results of the ASTRONAUT study do not support the routine administration of aliskiren in addition to standard therapy, to patients hospitalized for worsening chronic heart failure," the investigators concluded, adding that the subgroup analysis was "consistent with previous reports of poor outcomes  with the use of aliskiren in patients with diabetes already taking RAAS inhibitors."

Further studies will be necessary to evaluate renin inhibiting drugs in patients with diabetes, they added.

Dr. Gheorghiade reported financial relationships with 32 pharmaceutical companies, including Novartis Pharma AG, the study sponsor.

For patients hospitalized with heart failure, aliskiren added no significant benefit to standard therapy in preventing cardiovascular death or heart failure readmission.

The drug did, however, have some problematic effects on patients with diabetes, including significant increases in the risk of cardiovascular death and heart failure readmission at 6 months and all-cause death at 1 year.

The negative interaction between diabetes and aliskiren – an inhibitor of the angiotensin-renin-aldosterone system (RAAS) – is unclear, according to Dr. Mihai Gheorghiade and colleagues.

"[The issue] may be related to the increased risk of hypotension, hyperkalemia, and worsening renal function with the study drug," wrote Dr. Gheorghiade of Northwestern University, St. Louis, Mo., and his colleagues. The conclusions were published in the March 10 issue of JAMA and simultaneously presented at the annual meeting of the American College of Cardiology in San Francisco (JAMA 2013;309:doi10.1001/jama.2013.1954).

The randomized, placebo-controlled ASTRONAUT trial compared 6-and 12-month outcomes of aliskiren plus standard therapy to standard therapy alone in patients hospitalized with heart failure. 

The study randomized 1,639 patients; 1,615 were included in the final efficacy analysis. Patients in the investigational arm received 150 mg aliskiren daily in addition to standard treatment. Standard treatment was at the treating physician’s discretion, and could include, among others, diuretics, digoxin, ACE inhibitors, angiotensin receptor blockers, and beta-blockers. The study enrolled patients from 2009-2011; the median follow-up was 11 months

The patients were a mean of 65 years old. Their mean left ventricular ejection fraction was 28%, and mean estimated glomerular filtration rate was 67 mL/min/1.73 m³.  Nearly half (41%) had diabetes.

At admission, the mean N-terminal pro–brain natriuretic peptide (NT-proBNP) level was 4,239 pg/mL. Other drugs taken at baseline included diuretics (96%), beta-blockers (82%), ACE inhibitors or ARBs (84%), and mineralocorticoid antagonists (57%).

The primary efficacy endpoint was a combination of cardiovascular death or heart failure readmission within 6 months. This occurred in 201 (25%) of the aliskiren group and 214 (26%) of the placebo group – a nonsignificant difference. Nor were there significant differences when CV death and readmission were examined separately.

The main secondary endpoint was the composite of cardiovascular death or heart failure readmission at 12 months; again, there was no significant between-group difference (35% vs. 37%), although the events were numerically less in the aliskiren group than the control group (283 vs. 301). Parsing down the number of first cardiovascular events after treatment, the investigators did find that myocardial infarction was significantly less common in the aliskiren group (2% vs. 5%; HR 0.93; P = 0.009).

A subgroup analysis found that the drug was especially problematic for patients with diabetes. Compared to patients without the disorder who had standard treatment, diabetic patients who took aliskiren were 16% more likely to experience cardiovascular death or heart failure readmission by 6 months, and 64% more likely to experience all-cause death by 12 months.

During the treatment period, death occurred in 24% of patients with diabetes who took aliskiren, compared with 17% who took placebo – also a significant difference.

"In contrast, the rates of death among patients without a history [of diabetes] were 15% and 20% in the aliskiren and placebo groups, respectively," the authors wrote.

A number of adverse events were significantly higher in the aliskiren group, including hyperkalemia (14% vs. 13%) and severe hyperkalemia (8% vs. 5%). Hyperkalemia-related events occurred in 21% of the aliskiren group and 17% of the control group. Hypotension was also more common in the aliskiren group (17% vs. 13%). Decreased eGFR was significantly more common among those taking the study drug (11% vs. 9%), as were events potentially related to renal dysfunction (17% vs. 12%).

"The results of the ASTRONAUT study do not support the routine administration of aliskiren in addition to standard therapy, to patients hospitalized for worsening chronic heart failure," the investigators concluded, adding that the subgroup analysis was "consistent with previous reports of poor outcomes  with the use of aliskiren in patients with diabetes already taking RAAS inhibitors."

Further studies will be necessary to evaluate renin inhibiting drugs in patients with diabetes, they added.

Dr. Gheorghiade reported financial relationships with 32 pharmaceutical companies, including Novartis Pharma AG, the study sponsor.

SAN FRANCISCO – Treatment of anemic heart failure patients with the erythropoiesis-stimulating agent darbepoetin alfa failed to produce any clinically meaningful improvements and significantly raised the incidence of ischemic stroke and thrombotic events in a randomized, multicenter trial with more than 2,200 patients.

 “Our findings do not support the use of erythropoiesis-stimulating agents to reduced cardiovascular morbidity and mortality in patients with systolic heart failure and mild-to-moderately severe anemia,” Dr. Karl Swedberg said on March 10 at the annual meeting of the American College of Cardiology.

Patients with heart failure also often have anemia, and results from small studies had suggested that increasing patients’ hemoglobin levels could improve their functional capacity. In addition, results from observational studies had shown worse outcomes in heart failure patients with hemoglobin levels less than 12.0 g/dL, and that a 1.0 g/dL change in hemoglobin level linked with a difference of 15-20 percentage points in all-cause mortality.

But the results of the current study called into question whether anemia plays any primary role in worsened outcomes.

Treatment with darbepoetin had “questionable clinical impact and increased thromboembolic events.” The treatment also significantly linked with an increased rate of ischemic cerebrovascular disorders that was “worrying. Our findings suggest that the hemoglobin level, like other surrogates, is simply a marker of poor prognosis in heart failure rather than a therapeutic target," said Dr. Swedberg, professor of medicine at the University of Gothenburg, Sweden. Simultaneously with his report at the meeting, the findings were also published online (N. Engl. J. Med. 2013; 368: doi:10.1056/NEJMoa1214865).

The Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial enrolled 2,278 patients with New York Heart Association class II-IV heart failure and a hemoglobin level of 9.0-12.0 g/dL at 453 sites in 33 countries during June 2006–May 2012. All patients also had a left ventricular ejection fraction of 40% or less. The study excluded patients with iron deficiency (transferrin saturation of less than 15%), evidence or bleeding or other causes of anemia, and patients with a high serum creatinine level or blood pressure above 160/100 mm Hg. The median age of the enrolled patients was 72 years, 65% had class III or IV heart failure, and their median ejection fraction was 31%. Median hemoglobin at entry was 11.2 g/dL.

The 1,136 patients assigned to receive darbepoetin injections began at a dose of 0.75 mcg/kg body weight once every 2 weeks; once they achieved a hemoglobin level of 13.0 g/dL treatment scaled back to once monthly, and treatment was continued to maintain a hemoglobin level of 13.0-14.5 g/dL. The difference in hemoglobin levels between these patients and the 1,142 randomized to the placebo control group became statistically significant after 1 month and remained significant through the study, which had a median follow-up of 28 months. The median monthly darbepoetin dosage was 167 mcg. When patients’ transferrin saturation fell below 20% they received supplemental iron.

The study’s primary endpoint was the combined rate of all-cause death and hospitalization for worsening heart failure. This occurred in 51% of the patients treated with darbepoetin alfa and 50% of those who received placebo, a difference that was not statistically significant. The result was consistent across all subgroups examined, and was not affected by adjustment for baseline differences between the two treatment arms. Total mortality was also similar between the two groups, 42% in the darbepoetin-treated patients and 40% in the controls.

The total number of hospitalizations for heart failure was 572 in the darbepoetin arm and 695 among the placebo patients, a difference that just missed being statistically significant (P = 0.06).

The overall Summary Score of the Kansas City Cardiomyopathy Questionnaire, a measure of quality of life in heart failure patients, was 6.68 in the darbepoetin-treated patients and 4.48 in the placebo patients, an average 2.2 point difference that was statistically significant. But the percent of patients with at least a 5-point increase in their score over baseline – a clinically meaningful increase – was 53% in the darbepoetin group and 48% in the placebo arm, a difference that fell short of statistical significant (P = 0.06).

The rate of study drug discontinuations due to adverse events was similar in the two arms. The rate of any embolic and thrombotic event was 14% in the darbepoetin patients and 10% in the placebo patients, a statistically significant difference. The rate of ischemic cerebrovascular events was 5% in the darbepoetin arm and 3% in the placebo arm, a statistically significant difference, although the overall rate of all cerebrovascular disorders – ischemic or hemorrhagic – was not significantly different between the two treatment groups. Episodes of septic shock were also significantly more frequent in the darbepoetin-treatment patients.

Dr. Swedberg cautioned against extrapolating the lack of benefit from darbepoetin in this patient population to other types of patients with anemia.

"I would be very careful to extend our findings to other situations because heart failure is a very special situation, with a lot of neurohormonal activation on top of other effects on the cardiorenal axis," he said. In addition, he stressed that the findings should not dissuade clinicians from administering an erythropoiesis-stimulating agent to patients with systolic heart failure and more severe anemia.

The RED-HF study was sponsored by Amgen, the company that market darbepoetin alfa (Aranesp). Dr. Swedberg said that he has been a consultant to and lecturer on behalf of Amgen as well as Novartis and Servier.

SAN FRANCISCO – Treatment of anemic heart failure patients with the erythropoiesis-stimulating agent darbepoetin alfa failed to produce any clinically meaningful improvements and significantly raised the incidence of ischemic stroke and thrombotic events in a randomized, multicenter trial with more than 2,200 patients.

 “Our findings do not support the use of erythropoiesis-stimulating agents to reduced cardiovascular morbidity and mortality in patients with systolic heart failure and mild-to-moderately severe anemia,” Dr. Karl Swedberg said on March 10 at the annual meeting of the American College of Cardiology.

Patients with heart failure also often have anemia, and results from small studies had suggested that increasing patients’ hemoglobin levels could improve their functional capacity. In addition, results from observational studies had shown worse outcomes in heart failure patients with hemoglobin levels less than 12.0 g/dL, and that a 1.0 g/dL change in hemoglobin level linked with a difference of 15-20 percentage points in all-cause mortality.

But the results of the current study called into question whether anemia plays any primary role in worsened outcomes.

Treatment with darbepoetin had “questionable clinical impact and increased thromboembolic events.” The treatment also significantly linked with an increased rate of ischemic cerebrovascular disorders that was “worrying. Our findings suggest that the hemoglobin level, like other surrogates, is simply a marker of poor prognosis in heart failure rather than a therapeutic target," said Dr. Swedberg, professor of medicine at the University of Gothenburg, Sweden. Simultaneously with his report at the meeting, the findings were also published online (N. Engl. J. Med. 2013; 368: doi:10.1056/NEJMoa1214865).

The Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial enrolled 2,278 patients with New York Heart Association class II-IV heart failure and a hemoglobin level of 9.0-12.0 g/dL at 453 sites in 33 countries during June 2006–May 2012. All patients also had a left ventricular ejection fraction of 40% or less. The study excluded patients with iron deficiency (transferrin saturation of less than 15%), evidence or bleeding or other causes of anemia, and patients with a high serum creatinine level or blood pressure above 160/100 mm Hg. The median age of the enrolled patients was 72 years, 65% had class III or IV heart failure, and their median ejection fraction was 31%. Median hemoglobin at entry was 11.2 g/dL.

The 1,136 patients assigned to receive darbepoetin injections began at a dose of 0.75 mcg/kg body weight once every 2 weeks; once they achieved a hemoglobin level of 13.0 g/dL treatment scaled back to once monthly, and treatment was continued to maintain a hemoglobin level of 13.0-14.5 g/dL. The difference in hemoglobin levels between these patients and the 1,142 randomized to the placebo control group became statistically significant after 1 month and remained significant through the study, which had a median follow-up of 28 months. The median monthly darbepoetin dosage was 167 mcg. When patients’ transferrin saturation fell below 20% they received supplemental iron.

The study’s primary endpoint was the combined rate of all-cause death and hospitalization for worsening heart failure. This occurred in 51% of the patients treated with darbepoetin alfa and 50% of those who received placebo, a difference that was not statistically significant. The result was consistent across all subgroups examined, and was not affected by adjustment for baseline differences between the two treatment arms. Total mortality was also similar between the two groups, 42% in the darbepoetin-treated patients and 40% in the controls.

The total number of hospitalizations for heart failure was 572 in the darbepoetin arm and 695 among the placebo patients, a difference that just missed being statistically significant (P = 0.06).

The overall Summary Score of the Kansas City Cardiomyopathy Questionnaire, a measure of quality of life in heart failure patients, was 6.68 in the darbepoetin-treated patients and 4.48 in the placebo patients, an average 2.2 point difference that was statistically significant. But the percent of patients with at least a 5-point increase in their score over baseline – a clinically meaningful increase – was 53% in the darbepoetin group and 48% in the placebo arm, a difference that fell short of statistical significant (P = 0.06).

The rate of study drug discontinuations due to adverse events was similar in the two arms. The rate of any embolic and thrombotic event was 14% in the darbepoetin patients and 10% in the placebo patients, a statistically significant difference. The rate of ischemic cerebrovascular events was 5% in the darbepoetin arm and 3% in the placebo arm, a statistically significant difference, although the overall rate of all cerebrovascular disorders – ischemic or hemorrhagic – was not significantly different between the two treatment groups. Episodes of septic shock were also significantly more frequent in the darbepoetin-treatment patients.

Dr. Swedberg cautioned against extrapolating the lack of benefit from darbepoetin in this patient population to other types of patients with anemia.

"I would be very careful to extend our findings to other situations because heart failure is a very special situation, with a lot of neurohormonal activation on top of other effects on the cardiorenal axis," he said. In addition, he stressed that the findings should not dissuade clinicians from administering an erythropoiesis-stimulating agent to patients with systolic heart failure and more severe anemia.

The RED-HF study was sponsored by Amgen, the company that market darbepoetin alfa (Aranesp). Dr. Swedberg said that he has been a consultant to and lecturer on behalf of Amgen as well as Novartis and Servier.

SAN FRANCISCO – Treatment of anemic heart failure patients with the erythropoiesis-stimulating agent darbepoetin alfa failed to produce any clinically meaningful improvements and significantly raised the incidence of ischemic stroke and thrombotic events in a randomized, multicenter trial with more than 2,200 patients.

 “Our findings do not support the use of erythropoiesis-stimulating agents to reduced cardiovascular morbidity and mortality in patients with systolic heart failure and mild-to-moderately severe anemia,” Dr. Karl Swedberg said on March 10 at the annual meeting of the American College of Cardiology.

Patients with heart failure also often have anemia, and results from small studies had suggested that increasing patients’ hemoglobin levels could improve their functional capacity. In addition, results from observational studies had shown worse outcomes in heart failure patients with hemoglobin levels less than 12.0 g/dL, and that a 1.0 g/dL change in hemoglobin level linked with a difference of 15-20 percentage points in all-cause mortality.

But the results of the current study called into question whether anemia plays any primary role in worsened outcomes.

Treatment with darbepoetin had “questionable clinical impact and increased thromboembolic events.” The treatment also significantly linked with an increased rate of ischemic cerebrovascular disorders that was “worrying. Our findings suggest that the hemoglobin level, like other surrogates, is simply a marker of poor prognosis in heart failure rather than a therapeutic target," said Dr. Swedberg, professor of medicine at the University of Gothenburg, Sweden. Simultaneously with his report at the meeting, the findings were also published online (N. Engl. J. Med. 2013; 368: doi:10.1056/NEJMoa1214865).

The Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial enrolled 2,278 patients with New York Heart Association class II-IV heart failure and a hemoglobin level of 9.0-12.0 g/dL at 453 sites in 33 countries during June 2006–May 2012. All patients also had a left ventricular ejection fraction of 40% or less. The study excluded patients with iron deficiency (transferrin saturation of less than 15%), evidence or bleeding or other causes of anemia, and patients with a high serum creatinine level or blood pressure above 160/100 mm Hg. The median age of the enrolled patients was 72 years, 65% had class III or IV heart failure, and their median ejection fraction was 31%. Median hemoglobin at entry was 11.2 g/dL.

The 1,136 patients assigned to receive darbepoetin injections began at a dose of 0.75 mcg/kg body weight once every 2 weeks; once they achieved a hemoglobin level of 13.0 g/dL treatment scaled back to once monthly, and treatment was continued to maintain a hemoglobin level of 13.0-14.5 g/dL. The difference in hemoglobin levels between these patients and the 1,142 randomized to the placebo control group became statistically significant after 1 month and remained significant through the study, which had a median follow-up of 28 months. The median monthly darbepoetin dosage was 167 mcg. When patients’ transferrin saturation fell below 20% they received supplemental iron.

The study’s primary endpoint was the combined rate of all-cause death and hospitalization for worsening heart failure. This occurred in 51% of the patients treated with darbepoetin alfa and 50% of those who received placebo, a difference that was not statistically significant. The result was consistent across all subgroups examined, and was not affected by adjustment for baseline differences between the two treatment arms. Total mortality was also similar between the two groups, 42% in the darbepoetin-treated patients and 40% in the controls.

The total number of hospitalizations for heart failure was 572 in the darbepoetin arm and 695 among the placebo patients, a difference that just missed being statistically significant (P = 0.06).

The overall Summary Score of the Kansas City Cardiomyopathy Questionnaire, a measure of quality of life in heart failure patients, was 6.68 in the darbepoetin-treated patients and 4.48 in the placebo patients, an average 2.2 point difference that was statistically significant. But the percent of patients with at least a 5-point increase in their score over baseline – a clinically meaningful increase – was 53% in the darbepoetin group and 48% in the placebo arm, a difference that fell short of statistical significant (P = 0.06).

The rate of study drug discontinuations due to adverse events was similar in the two arms. The rate of any embolic and thrombotic event was 14% in the darbepoetin patients and 10% in the placebo patients, a statistically significant difference. The rate of ischemic cerebrovascular events was 5% in the darbepoetin arm and 3% in the placebo arm, a statistically significant difference, although the overall rate of all cerebrovascular disorders – ischemic or hemorrhagic – was not significantly different between the two treatment groups. Episodes of septic shock were also significantly more frequent in the darbepoetin-treatment patients.

Dr. Swedberg cautioned against extrapolating the lack of benefit from darbepoetin in this patient population to other types of patients with anemia.

"I would be very careful to extend our findings to other situations because heart failure is a very special situation, with a lot of neurohormonal activation on top of other effects on the cardiorenal axis," he said. In addition, he stressed that the findings should not dissuade clinicians from administering an erythropoiesis-stimulating agent to patients with systolic heart failure and more severe anemia.

The RED-HF study was sponsored by Amgen, the company that market darbepoetin alfa (Aranesp). Dr. Swedberg said that he has been a consultant to and lecturer on behalf of Amgen as well as Novartis and Servier.

Spironolactone significantly improved left ventricular diastolic function and remodeling in a 1-year study of ambulatory patients who had heart failure with preserved ejection fraction, but that benefit did not translate into improvements in HF symptoms or quality of life, according to a report in the Feb. 27 issue of JAMA.

In the multicenter, double-blind Aldosterone Receptor Blockade in Diastolic HF (Aldo-DHF) clinical trial, 213 men and women aged 50 and older were randomly assigned to receive daily oral spironolactone and 209 to receive a matching placebo for 1 year. Patients on spironolactone had significantly increased LV ejection fraction, decreased LV end-diastolic diameter and LV mass index, and reduced systolic blood pressure, reported Dr. Burkert M. Pieske, professor and head of the department of cardiology at Medical University of Graz, Austria, and his associates.

Mitchel L. Zoler/IMNG Medical Media

The drug failed to improve HF symptoms, exercise capacity, depressive symptoms, or quality of life, compared with placebo. "Our study population may have been too young or too healthy, or the treatment period may have been too short, for observing a translation of improved diastolic function into a clinical benefit," the investigators said (JAMA 2013;309:781-91).

These results were presented at the annual meeting of the European Society of Cardiology in Munich last summer, and reported by this newspaper.

Experts reacting to the news at the meeting expressed similar misgivings.

"It was not all good news. Patients had an increase in their potassium level, and even more concerning, they had a reduction in their glomerular filtration rate, an average reduction of about 5 mL/min," commented Dr. Stefan D. Anker, professor of medicine at Charité Medical University in Berlin. In addition, the distance walked on the 6-minute walk test was "slightly decreased with spironolactone. Even though it was a small change of 15 m, it was statistically significant," he noted. On top of all this, "worsening of anemia was seen in patients," he added.

Mitchel L. Zoler/IMNG Medical Media

Study discussant Dr. John G.F. Cleland said that although the Aldo-DHF study adds important new information on the progression of diastolic heart failure as seen in the control group, it wasn’t really was a study of diastolic heart failure. Few of the patients were on diuretic drugs, at entry they had fairly normal levels of NT-proBNP, they had mild abnormalities detected by echocardiography, and they exhibited mild deficits in cardiopulmonary exercise testing, said Dr. Cleland, professor of cardiology at the University of Hull, Kingston-upon-Hull, England.

Aldo-DHF was supported by the German-Austrian Heart Failure Study Group and the German Competence Network of Heart Failure. Dr. Edelmann and his associates reported numerous ties to industry sources.

cardnews@elsevier.com

Spironolactone significantly improved left ventricular diastolic function and remodeling in a 1-year study of ambulatory patients who had heart failure with preserved ejection fraction, but that benefit did not translate into improvements in HF symptoms or quality of life, according to a report in the Feb. 27 issue of JAMA.

In the multicenter, double-blind Aldosterone Receptor Blockade in Diastolic HF (Aldo-DHF) clinical trial, 213 men and women aged 50 and older were randomly assigned to receive daily oral spironolactone and 209 to receive a matching placebo for 1 year. Patients on spironolactone had significantly increased LV ejection fraction, decreased LV end-diastolic diameter and LV mass index, and reduced systolic blood pressure, reported Dr. Burkert M. Pieske, professor and head of the department of cardiology at Medical University of Graz, Austria, and his associates.

Mitchel L. Zoler/IMNG Medical Media

The drug failed to improve HF symptoms, exercise capacity, depressive symptoms, or quality of life, compared with placebo. "Our study population may have been too young or too healthy, or the treatment period may have been too short, for observing a translation of improved diastolic function into a clinical benefit," the investigators said (JAMA 2013;309:781-91).

These results were presented at the annual meeting of the European Society of Cardiology in Munich last summer, and reported by this newspaper.

Experts reacting to the news at the meeting expressed similar misgivings.

"It was not all good news. Patients had an increase in their potassium level, and even more concerning, they had a reduction in their glomerular filtration rate, an average reduction of about 5 mL/min," commented Dr. Stefan D. Anker, professor of medicine at Charité Medical University in Berlin. In addition, the distance walked on the 6-minute walk test was "slightly decreased with spironolactone. Even though it was a small change of 15 m, it was statistically significant," he noted. On top of all this, "worsening of anemia was seen in patients," he added.

Mitchel L. Zoler/IMNG Medical Media

Study discussant Dr. John G.F. Cleland said that although the Aldo-DHF study adds important new information on the progression of diastolic heart failure as seen in the control group, it wasn’t really was a study of diastolic heart failure. Few of the patients were on diuretic drugs, at entry they had fairly normal levels of NT-proBNP, they had mild abnormalities detected by echocardiography, and they exhibited mild deficits in cardiopulmonary exercise testing, said Dr. Cleland, professor of cardiology at the University of Hull, Kingston-upon-Hull, England.

Aldo-DHF was supported by the German-Austrian Heart Failure Study Group and the German Competence Network of Heart Failure. Dr. Edelmann and his associates reported numerous ties to industry sources.

cardnews@elsevier.com

Spironolactone significantly improved left ventricular diastolic function and remodeling in a 1-year study of ambulatory patients who had heart failure with preserved ejection fraction, but that benefit did not translate into improvements in HF symptoms or quality of life, according to a report in the Feb. 27 issue of JAMA.

In the multicenter, double-blind Aldosterone Receptor Blockade in Diastolic HF (Aldo-DHF) clinical trial, 213 men and women aged 50 and older were randomly assigned to receive daily oral spironolactone and 209 to receive a matching placebo for 1 year. Patients on spironolactone had significantly increased LV ejection fraction, decreased LV end-diastolic diameter and LV mass index, and reduced systolic blood pressure, reported Dr. Burkert M. Pieske, professor and head of the department of cardiology at Medical University of Graz, Austria, and his associates.

Mitchel L. Zoler/IMNG Medical Media

The drug failed to improve HF symptoms, exercise capacity, depressive symptoms, or quality of life, compared with placebo. "Our study population may have been too young or too healthy, or the treatment period may have been too short, for observing a translation of improved diastolic function into a clinical benefit," the investigators said (JAMA 2013;309:781-91).

These results were presented at the annual meeting of the European Society of Cardiology in Munich last summer, and reported by this newspaper.

Experts reacting to the news at the meeting expressed similar misgivings.

"It was not all good news. Patients had an increase in their potassium level, and even more concerning, they had a reduction in their glomerular filtration rate, an average reduction of about 5 mL/min," commented Dr. Stefan D. Anker, professor of medicine at Charité Medical University in Berlin. In addition, the distance walked on the 6-minute walk test was "slightly decreased with spironolactone. Even though it was a small change of 15 m, it was statistically significant," he noted. On top of all this, "worsening of anemia was seen in patients," he added.

Mitchel L. Zoler/IMNG Medical Media

Study discussant Dr. John G.F. Cleland said that although the Aldo-DHF study adds important new information on the progression of diastolic heart failure as seen in the control group, it wasn’t really was a study of diastolic heart failure. Few of the patients were on diuretic drugs, at entry they had fairly normal levels of NT-proBNP, they had mild abnormalities detected by echocardiography, and they exhibited mild deficits in cardiopulmonary exercise testing, said Dr. Cleland, professor of cardiology at the University of Hull, Kingston-upon-Hull, England.

Aldo-DHF was supported by the German-Austrian Heart Failure Study Group and the German Competence Network of Heart Failure. Dr. Edelmann and his associates reported numerous ties to industry sources.

cardnews@elsevier.com