Sacubitril/valsartan for treatment of symptomatic non-obstructive hypertrophic cardiomyopathy: a randomised, controlled, phase II clinical trial (SILICOFCM)

Abstract Aim To evaluate the effect of sacubitril/valsartan on exercise capacity, cardiac structure, and function in patients with hypertrophic cardiomyopathy (HCM). Methods Phase II, randomised, open-label multicentre study enrolled adult patients with symptomatic non-obstructive HCM (NYHA class I–III) who were randomly assigned (2:1) to receive sacubitril/valsartan (target dose 97/103mg) or usual care for 16 weeks. Primary endpoint was a change in peak oxygen consumption (peak VO2). Secondary endpoints included echocardiography measures of cardiac structure and function, natriuretic peptides and other biomarkers, and Minnesota Living with Heart Failure quality of life (QoL). Results Between May 2018 and November 2021, 354 patients were screened for eligibility, 115 patients (mean age 58 years [SD 11], 37% women) met the study inclusion criteria and were randomly assigned to sacubitril/valsartan (N=79) or usual care (N=36). At 16 weeks, there was no significant change in peak VO2 from baseline in sacubitril/valsartan (15.3 [4.3] vs 15.9 [4.3] ml/kg/min, p=0.13), or usual care group (p=0.47). There was a significant reduction in ventilatory efficiency slope (30.1 [7] vs 28.4 [4.9], p=0.03), but not in the control group (p=0.09). No significant changes were found in systolic or diastolic function, cardiac structure, or plasma biomarkers. The QoL score decreased significantly in the sacubitril/valsartan by 6 points (p=0.005) but not in the usual care group (p=0.66). Conclusion In patients with hypertrophic cardiomyopathy, 16 weeks of treatment with sacubitril/valsartan was well tolerated and contributed to a significant improvement in ventilatory efficiency and quality of life but not in exercise capacity or cardiac function.