Angiotensin receptor neprilysin inhibition versus individualized RAAS blockade: design and rationale of the PARALLAX trial

• Main Authors: Rolf Wachter, Sanjiv J. Shah, Martin R. Cowie, Peter Szecsödy, Victor Shi, Ghionul Ibram, Ziqiang Zhao, Jianjian Gong, Sven Klebs, Burkert Pieske
• Format: Article
• Language: English
• Published: Wiley 2020-06-01
• Series: ESC Heart Failure
• Subjects: Heart failure with preserved ejection fraction; Heart failure with mid‐range ejection fraction; Functional capacity; Quality of life; Neprilysin inhibition; Randomized controlled trial
• Online Access: https://doi.org/10.1002/ehf2.12694

Abstract Aims Although the effect of the angiotensin receptor blocker neprilysin inhibitor (ARNI) sacubitril/valsartan on heart failure (HF) hospitalizations and cardiovascular death has been evaluated, its effects on functional capacity in patients with HF and ejection fraction (EF) >40% has yet to be determined. In addition, no prior studies have compared sacubitril/valsartan with angiotensin‐converting enzyme inhibitor therapy. We sought to compare the effect of ARNI to background‐medication‐based individualized comparators (BMICs) on N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), functional capacity [6 min walk distance (6MWD)], symptoms, and quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ)] in patients with HF and EF >40% in a randomized clinical trial. Methods PARALLAX is a prospective, randomized, controlled, double‐blind multicentre clinical trial in patients with chronic symptomatic HF with EF >40%, New York Heart Association (NYHA) class II–IV symptoms, elevated natriuretic peptides, and evidence of structural heart disease. Eligible patients are randomized to sacubitril/valsartan vs. BMIC for cardiovascular and related co‐morbidities. BMIC includes (i) enalapril, (ii) valsartan, and (iii) placebo depending on the type of medical therapy prior to enrolment. The primary endpoints are the change in plasma NT‐proBNP concentration from baseline to 12 weeks and the change from baseline in 6MWD distance at 24 weeks. The secondary endpoints assess quality of life and symptom burden. Conclusions PARALLAX will determine if sacubitril/valsartan compared with standard medical therapy for co‐morbidities improves NT‐proBNP levels, exercise capacity, quality of life, and symptom burden in HF patients with EF >40%.