Efficacy and safety of sacubitril/valsartan compared with enalapril in patients with chronic heart failure and reduced ejection fraction: Results from PARADIGM-HF India sub-study

OBJECTIVES: To determine efficacy and safety of sacubitril/valsartan compared with enalapril in Indian patients of PARADIGM-HF trial. METHODS: A randomized, double-blind, active-controlled, phase III sub-study (NCT01035255) was conducted between April 2010 and May 2014. Patients with chronic heart failure (HF), aged >18 years with left ventricular ejection fraction ≤40% were randomized (1:1) to receive either sacubitril/valsartan 200 mg twice-daily or enalapril 10 mg twice-daily. The primary endpoint was to compare efficacy of sacubitril/valsartan to enalapril in delaying time-to-first occurrence of the composite endpoint (cardiovascular [CV] death or HF hospitalization). RESULTS: The trial was stopped after a median follow-up of 27 months, because the boundary for benefit with sacubitril/valsartan had crossed. Among 637 Indian patients in PARADIGM-HF (sacubitril/valsartan, n = 322 and enalapril, n = 315), the primary outcome, CV death, and the first hospitalization for HF occurred in 21.81% and 24.76% (HR 0.89; 95% CI, 0.646–1.231), 17.45% and 20.63% (HR 0.87; 95% CI, 0.605–1.236), and 7.48% and 9.52% (HR 0.78; 95% CI, 0.461–1.350) patients in the sacubitril/valsartan and enalapril group, respectively. The all-cause mortality (19.0% vs. 21.9%) and adverse events (78.4% vs. 82.2%) were comparatively lower in the sacubitril/valsartan than enalapril group. No significant difference was seen between the benefits of treatment in Indian and the total PARADIGM-HF cohort (p value for interaction >0.05). CONCLUSION: Results support the use of sacubitril/valsartan in Indian patients with chronic HF with reduced ejection fraction with treatment benefits similar to global PARADIGM-HF cohort.