New combo therapy for chronic heart failure
Entresto® is a newly approved combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker (ARB) for patients who have chronic heart failure NYHA Class II-IV and reduced ejection fraction.
Sacubitril exerts its effect by inhibiting the metabolism of natriuretic peptides, thereby subsequently augmenting excretion of sodium in the urine. Valsartan selectively blocks angiotension II receptors which reduces angiotensin-mediated aldosterone release and decreases vasoconstriction caused by dysregulation of the renin-angiotensin aldosterone system.1
The American College of Cardiology, the American Heart Association and the Heart Failure Society of America published a consensus statement of the newest pharmacological recommendations in the management of heart failure based on the latest literature.2
This update includes recommendations for the angiotensin receptorneprilysin inhibitor (ARNI) in NYHA class II-IV heart failure with reduced ejection fraction. When ARNI therapy is combined with a recommended beta-blocker and aldosterone antagonist, the risk of morbidity and mortality is reduced.
This is a class I-BR recommendation, a strong recommendation based on moderate quality of evidence from a randomized controlled trial. The PARADIGM- HF study was an RCT involving over 8,000 patients given either the ARNI or enalapril. The primary endpoint was a composite of cardiovascular-related deaths or first hospitalization.
There was a 20% decrease in CV-related deaths (HR: 0.80 [95% CI: 0.71–0.89; p<0.001]) and a 21% decrease in first hospitalizations for heart failure (HR: 0.79 [(95% CI: 0.71– 0.89; p<0.001]), although there was an increase in the incidence of hypotension in the ARNI group (14% vs. 9.2%; p<0.001).
Treatment-naïve patients, or those on a low dose ACE inhibitor or ARB therapy should be started on the sacubitril 24 mg/valsartan 26 mg strength, twice daily. The 49mg/51mg twice daily dose can be initiated in those switching from greater than 10 mg of enalapril or 160 mg or more of valsartan daily.