The angiotensin-receptor-neprilysin inhibitor ( ARNI ) Valsartan / Sacubitril ( Entresto; LCZ696 ) reduced cardiovascular deaths and all-cause mortality compared with Enalapril in patients with chronic heart failure ( HF ) in the prospective comparison of ARNI with PARADIGM-HF ( Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure ) trial.
To more completely understand the components of this mortality benefit, researchers examined the effect of combination of Valsartan and Sacubitril on mode of death.
PARADIGM-HF was a prospective, double-blind, randomized trial in 8399 patients with chronic heart failure, NYHA ( New York Heart Association ) Class II–IV symptoms, and left ventricular ejection fraction less than or equal to 40% receiving guideline-recommended medical therapy and followed for a median of 27 months.
Mode of death was adjudicated by a blinded clinical endpoints committee.
The majority of deaths were cardiovascular ( 80.9% ), and the risk of cardiovascular death was significantly reduced by treatment with Valsartan / Sacubitril ( hazard ratio, HR 0.80, 95% CI 0.72–0.89, P less than 0.001 ).
Among cardiovascular deaths, both sudden cardiac death ( HR=0.80, 95% CI 0.68–0.94, P = 0.008 ) and death due to worsening heart failure ( HR=0.79, 95% CI 0.64–0.98, P = 0.034 ) were reduced by treatment with Valsartan / Sacubitril compared with Enalapril.
Deaths attributed to other cardiovascular causes, including myocardial infarction and stroke, were infrequent and distributed evenly between treatment groups, as were non-cardiovascular deaths.
In conclusion Valsartan / Sacubitril was superior to Enalapril in reducing both sudden cardiac deaths and deaths from worsening heart failure, which accounted for the majority of cardiovascular deaths. ( Xagena )
Desai AS et al, Eur Heart J 2015; 36: 1990-1997