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

Rolf Wachter*, Sanjiv J. Shah, Martin R. Cowie, Peter Szecsödy, Victor Shi, Ghionul Ibram, Ziqiang Zhao, Jianjian Gong, Sven Klebs, Burkert Pieske

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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%.

Original languageEnglish (US)
Pages (from-to)856-864
Number of pages9
JournalESC Heart Failure
Issue number3
StatePublished - Jun 1 2020


  • Functional capacity
  • Heart failure with mid-range ejection fraction
  • Heart failure with preserved ejection fraction
  • Neprilysin inhibition
  • Quality of life
  • Randomized controlled trial

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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