No improved patient-oriented outcomes with sacubitril/valsartan in adults with heart failure and preserved EF (PARALLAX)

Reference

Pieske B, Wachter R, Shah SJ, et al, for the PARALLAX Investigators and Committee members. Effect of sacubitril/valsartan vs standard medical therapies on plasma NT-proBNP concentration and submaximal exercise capacity in patients with heart failure and preserved ejection fraction. The PARALLAX randomized clinical trial. JAMA 2021;326(19):1919-1929.

Synopsis

These investigators identified adults, 45 years or older, with symptomatic heart failure, elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, New York Heart Association (NYHA) class II–IV, a left ventricular ejection fraction of greater than 40%, and an impaired health-related quality of life as measured by a standard scoring tool. Patients taking an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) at baseline were required to have a history of hypertension. Eligible participants (N = 2566) were initially assigned to 1 of 3 strata based on medication prescribed by their treating clinician: ACE inhibitor (n = 1066), ARB (n = 1174), or no renin angiotensin system (RAS) inhibitor (n = 326). Within each stratum patients randomly received (concealed allocation assignment) either sacubitril/valsartan or the background medication (ie, ACE inhibitor, ARB, or placebo/no RAS inhibitor). Clinicians were instructed to up-titrate within 4 weeks to the maximally tolerated doses. Patients, clinicians, and individuals assessing outcomes remained masked to treatment group assignment. Complete follow-up occurred for more than 99% of patients at 24 weeks. Using intention-to-treat analysis, patients in the sacubitril/valsartan group had a significantly greater reduction in NT-proBNP levels than the combined comparator group (ACE inhibitor, ARB, or placebo/no RAS inhibitor). However, at 24 weeks, no group differences occurred in median change from baseline in the 6-minute walk distance, quality-of-life scores, or improvement in NYHA class. Adverse events, including hypotension, albuminuria, and hyperkalemia, occurred more often in the sacubitril/valsartan group.