PARADIGM-HF Post-Hoc Analysis Shows Sacubitril/Valsartan Significantly Improves Physical, Social Activity

Scott Solomon, MD, Brigham and Women's Hospital

Scott Solomon, MD

Results published today in JAMA Cardiology from a PARADIGM-HF post-hoc analysis demonstrates that treatment with sacubitril/valsartan (Entresto) significantly improved 7 of 10 types of physical and social activities at 8 months in heart failure patients with reduced ejection fraction (HFrEF) versus patients taking enalapril.

The improvement in combined physical and social activity of patients with Entresto versus enalapril was equivalent to a difference of 9 years of aging. The most significant developments included the ability to carry out household chores and the ability to conduct intimate/sexual relationships.

“What we’ve done now is we’ve looked at the way people feel, the symptoms that they have, the limitations that they have, both in physical and social domains,” Scott Solomon, MD, Brigham and Women’s Hospital, told MD Magazine. “What we found is that in virtually all of these domains, all of these questions, patients reported improvement in their limitations if they were randomized to sacubitril compared to those who were randomized to enalapril.”

Data examined the effect of treatment with Entresto on 10 activities related to certain physical and social limitations, 2 of the 8 key components of health-related quality of life, assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and reported by 7623 patients enrolled in the trial.

KCCQ, a self-administered HRQL measure developed and validated for heart failure patients, explored the effects on treatment with Entresto on dressing, showering, climbing a flight of stairs, walking 100 yards, visiting family or friends, jogging, gardening, hobbies, conducing household chores and intimate/sexual relationships.

Patients treated with Entresto improved 7 of the 10 activities at the pre-specified 8-month analysis when compared with enalapril, with the greatest improvements reported in ability to carry out household chores and ability to conduct intimate/sexual relationships. Physical and social improvements were observed in the 8-month visit, but importantly, were sustained in the 3-year follow-up period.

“We think this is very exciting because, in fact, most drugs that we have in heart failure that reduce morbidity and mortality, like ACE inhibitors and ARBs and beta blockers, have not really been shown to improve these measures of physical and social limitation and quality of life,” Solomon added. “So this is really the first pharmacologic therapy that shows both a reduction in morbidity and mortality and improvement in symptoms.”

In the trial, Entresto was shown to reduce risk of cardiovascular death or first heart failure hospitalization versus treatment with enalapril.

“As we all know, sacubitril improves morbidity and mortality in heart failure patients with reduced ejection fraction, but now we can also tell the patients that, in activities that you care about, these physical and social activities, you may experience improvement in those things that affect you on a day-to-day basis,” Alvin Chandra, MD, Brigham and Women’s Hospital, told MD Magazine.

Entresto, a twice-daily medicine reduces the strain on a failing heart, and is administered in conjunction with other heart failure therapies and in place of an ACE inhibitor or other angiotensin receptor blockers.

In the US, it’s indicated for the treatment of heart failure in patients with systolic dysfunction. In addition to reduced likelihood of cardiovascular death, all-cause mortality and heart failure hospitalization, Entresto may improve limitations in common activities in these patients.

The data were previously presented at the Heart Failure Society of America (HFSA) 21st Annual Scientific Meeting in September 2017.

The post-hoc analysis of PARADIGM-HF was published in JAMA Cardiology.