News | Heart Failure | May 15, 2021

Sacubitril/Valsartan Does Not Outperform ACE Inhibitor in Preventing Heart Failure After Heart Attack

Trial finds favorable safety but no significant reduction in subsequent heart failure or death

The combination heart failure drug sacubitril/valsartan did not significantly reduce the rate of heart failure or cardiovascular death following a heart attack compared to ramipril, an angiotensin converting enzyme (ACE) inhibitor. #ACC21 #ACC2021

The combination heart failure drug sacubitril/valsartan did not significantly reduce the rate of heart failure or cardiovascular death following a heart attack compared to ramipril, an angiotensin converting enzyme (ACE) inhibitor.

May 15, 2021 — The combination heart failure drug sacubitril/valsartan (Entresto) did not significantly reduce the rate of heart failure or cardiovascular death following a heart attack compared to ramipril, an angiotensin converting enzyme (ACE) inhibitor proven effective in improving survival following heart attacks. Findings from the PARADISE-MI trial were presented as a late-breaking study at the American College of Cardiology (ACC) 2021 virtual Scientific Session.

The study is the first large trial to examine whether sacubitril/valsartan can reduce heart failure and associated hospitalizations and deaths in patients post-heart attack who face a high risk of developing heart failure. Patients taking sacubitril/valsartan were about 10% less likely than those taking ramipril to experience the study’s primary endpoint (a composite of cardiovascular death, heart failure hospitalization or development of symptomatic heart failure) falling short of the prespecified threshold of a 15% reduction required to demonstrate statistically significant improvement.

However, according to the researchers, the trial found sacubitril/valsartan was well-tolerated, had a favorable safety profile and was associated with a trend toward improvement in the trial’s secondary endpoints, which included cardiovascular death or heart failure hospitalization; heart failure hospitalization or outpatient treatment for heart failure; cardiovascular death, non-fatal heart attack or non-fatal stroke; cardiovascular death and total hospitalizations for heart failure, heart attack or stroke; and death from any cause.

“Although we did not significantly reduce our primary endpoint, there were consistent findings that sacubitril/valsartan could represent an incremental improvement over ramipril,” said Marc Pfeffer, M.D., Ph.D., Distinguished Dzau Professor of Medicine at Harvard Medical School and cardiologist at Brigham and Women’s Hospital, and the study’s lead author. “The results are encouraging, especially when considering recurrent heart failure events and not just the first heart failure events, but the study is not definitive. We did notice several aspects of heart failure development that were lessened with sacubitril/valsartan but to investigate these observations would require further evaluations.”

Heart failure is a condition in which the heart becomes too weak or too stiff to pump blood effectively to the rest of the body, causing fatigue, swelling and shortness of breath. While a heart attack does not always lead to heart failure, heart attack survivors are eight times more likely to develop heart failure than those who have not had a heart attack, which has led to an increased emphasis on preventing heart failure in these patients.

The PARADISE-MI trial enrolled 5,669 patients in 41 countries who had survived a heart attack less than a week before enrolling in the study. None of the patients had heart failure, but all were considered to face a high risk of developing it based on a measure of their heart’s pumping ability or fluid buildup in the lungs as well as at least one of eight additional risk-enhancing factors. Most patients were already taking medications to reduce heart disease risk before their heart attack, including antiplatelet therapy, blood pressure lowering medications and cholesterol lowering medications.

Half of the participants were randomly assigned to receive sacubitril/valsartan and half received ramipril. Most achieved the full dose of their assigned medication and kept taking it throughout the trial, which had a median follow-up period of 23 months.

The rate of the composite primary endpoint was 10% lower in patients taking sacubitril/valsartan compared with those taking ramipril. In an exploratory analysis of the total burden of heart failure including recurrent events, there was a 21% reduction observed with sacubitril/valsartan compared to ramipril. The rate of adverse events was equivalent in both groups, with no significant differences in the rates of allergic swelling of the airways (angioedema), abnormal potassium levels, renal impairment or liver abnormalities. Patients taking sacubitril/valsartan showed a slightly higher rate of hypotension while patients taking ramipril were slightly more likely to report coughing. These findings offer further reassurance that sacubitril/valsartan is safe to use for patients with heart failure, the indication for which it has been approved, researchers said. “We found sacubitril/valsartan was as safe and well-tolerated as one of the best proven ACE inhibitors, even in an acutely ill population,” Pfeffer said. “This trial may not change guidelines, but it should make physicians even more comfortable using sacubitril/valsartan in their patients with heart failure.”

The study was funded by Novartis Pharmaceuticals.
 

Find links to more ACC 2021 late-breakers

Find more content on LAA Occlusion

Related Content

Some of the top technology news from ACC 2021. Top left, the LAAOS III trial showed benefit when surgeons seal off the LAA during other open heart procedures. Bottom left, the ReCor Paradise renal denervation system helped lower blood pressure in patients who did not respond to medication. Top right, for patients with both heart failure and AFib it makes no differences is therapy is focused on controlling the heart rhythm or heart rate. Bottom right, the FLOWER-MI trial found no benefit to FFR-guided PCI.

Some of the top technology news from ACC 2021. Top left, the LAAOS III trial showed benefit when surgeons seal off the LAA during other open heart procedures. Bottom left, the ReCor Paradise renal denervation system helped lower blood pressure in patients who did not respond to medication. Top right, for patients with both heart failure and AFib it makes no difference if therapy is focused on controlling the heart rhythm or heart rate. Bottom right, the FLOWER-MI trial found no benefit to FFR-guided PCI in STEMI with multi-vessel disease.

Feature | ACC | June 08, 2021 | By Dave Fornell, Editor
Here are the top 10 takeaways from the late-breaking studies on cardiovascular technologies presented at the 2021 ...
AMERICAN COLLEGE OF CARDIOLOGY (ACC) Late-breaking clinical trial study presentations at ACC.21. @ACC21 @ACC2021
Feature | ACC | May 18, 2021 | Dave Fornell, Editor
The latest cardiology practice-changing scientific breakthrough, late-breaking study presentations have been announce
To help monitor the health of ACC 2021 in-person attendees for signs of COVID infection, the meeting will use BioIntelliSense's wearable BioButton continuous wireless temperature and vital signs monitoring. The wearable monitor is the size of a coin and is disposable.

To help monitor the health of ACC 2021 in-person attendees for signs of COVID infection, the meeting will use BioIntelliSense's wearable BioButton continuous wireless temperature and vital signs monitoring. The wearable monitor is the size of a coin and is disposable.

News | ACC | February 09, 2021 | By Dave Fornell, Editor
UPDATE Feb 22, 2021 — ...
The American College of Cardiology (ACC) released a list of the latest practice-changing presentations at the ACC.20 annual meeting March 28-30, 2020, in Chicago. This includes five late-breaking clinical trial (LBCT) sessions and three featured clinical research sessions. There also are two LBCT deep-dive sessions where the experts will break down the hottest trials and attendees can find out what the impact might be on the practice of cardiology and patients.
Feature | ACC | April 09, 2020 | Dave Fornell, Editor
Here is the list of American College of Cardiology (ACC) practice-
ACC Cancels 2020 Conference Amid Coronavirus Concerns. #COVID19 #coronavirus #2019nCoV
Feature | ACC | March 09, 2020 | Dave Fornell, Editor
March 9, 2020 — Less than week after the American College of Cardiolog...
American College of Cardiology Names Douglas Drachman Next Annual Scientific Session Vice Chair

Image courtesy of Massachusetts General Hospital

News | ACC | October 08, 2019
Douglas Drachman, M.D., FACC, has been selected as the next vice chair of the American College of Cardiology’s (ACC)...
SyncVision iFR Co-registration from Philips Healthcare maps pressure readings onto angiogram. Results from an international study presented at ACC 2019 indicates pressure readings obtained using iFR (instantaneous wave-free ratio, also referred to as instant wave-free ratio or instant flow reserve) in coronary arteries may localize stenoses that remain after interventions. FFR in the cath lab.

SyncVision iFR Co-registration from Philips Healthcare maps pressure readings onto angiogram. Results from an international study presented at ACC 2019 indicates pressure readings obtained using iFR (instantaneous wave-free ratio, also referred to as instant wave-free ratio or instant flow reserve) in coronary arteries may localize stenoses that remain after interventions.

Feature | ACC | March 27, 2019 | Greg Freiherr, Contributing Editor
The fingerprints of value-added medicine were all over products and works-in-progress on the exhibit floor of the a

The opening late-breaking trial at ACC 2019 is the Apple Heart Study, a large-scale, app-based study to identify atrial fibrillation using a smartwatch. Earlier, smaller trials showed this approach might be used in a population health application to proactively identify AFib patients earlier.

Feature | ACC | March 19, 2019
The American College of Cardiology (ACC) released a list of the late
A patient who received HeartMate III LVAD system at ACC.18. The HeartMate 3 was the topic of of the the key late-breaking trials at #ACC18

A patient who received the HeartMate III LVAD system showing off his external battery pack. He served as a patient ambassador in the Abbott booth at ACC.18. The HeartMate III, with its magnetic levitated pump, showed a big reduction in clotting over previous LVADs in a key late-breaking trial at this year's conference.

Feature | ACC | March 27, 2018 | Dave Fornell
There were several notable presentations of new data on cardiovascular technologies at the recent 2018 American Colle