Sacubitril/valsartan for the treatment of non-obstructive hypertrophic cardiomyopathy: An open label randomized controlled trial (SILICOFCM)

Aim: Sacubitril/valsartan treatment reduces mortality and hospitalizations in heart failure with reduced ejection fraction but has limited application in hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the effect of sacubitril/valsartan on peak oxygen consumption (VO₂) in patients with non-obstructive HCM. 

Methods and results: This is a phase II, randomized, open-label multicentre study that enrolled adult patients with symptomatic non-obstructive HCM (New York Heart Association class I–III) who were randomly assigned (2:1) to receive sacubitril/valsartan (target dose 97/103 mg) or control for 16 weeks. The primary endpoint was a change in peak VO₂. Secondary endpoints included echocardiographic measures of cardiac structure and function, natriuretic peptides and other cardiac biomarkers, and Minnesota Living with Heart Failure quality of life. Between May 2018 and October 2021, 354 patients were screened for eligibility, 115 patients (mean age 58 years, 37% female) met the study inclusion criteria and were randomly assigned to sacubitril/valsartan (n = 79) or control (n = 36). At 16 weeks, there was no significant change in peak VO₂ from baseline in the sacubitril/valsartan (15.3 [4.3] vs. 15.9 [4.3] ml/kg/min, p = 0.13) or control group (p = 0.47). No clinically significant changes were found in blood pressure, cardiac structure and function, plasma biomarkers, or quality of life. 

Conclusion: In patients with HCM, a 16-week treatment with sacubitril/valsartan was well tolerated but had no effect on exercise capacity, cardiac structure, or function.