Efficacy and safety of combined neprilysin and RAS inhibition in heart failure: A meta-analysis of randomized controlled trials.

OBJECTIVES

Concerns about safety make physicians reluctant to prescribe neprilysin-renin-angiotensin system (RAS) inhibitors. This meta-analysis was performed to assess the efficacy and safety of combined neprilysin and RAS inhibition in heart failure.

BACKGROUND

Combined inhibitors of neprilysin and RAS reduced heart failure hospitalization and cardiovascular death. While adverse events of neprilysin-RAS inhibitors in clinical trials are still controversial.

METHODS

Medline, the Cochrane Library and Clinicaltrials.gov were searched for randomized controlled trials (RCTs). Twelve studies covering 21,212 patients were eligible for inclusion.

RESULTS

Compared with RAS inhibition, neprilysin-RAS inhibition had a significant decrease in the mortality of heart failure [Odds Ratio (OR) 0.84; 95% Confidence Interval (CI) 0.78-0.91; P < 0.05], cardiovascular death (OR 0.78; 95% CI 0.69-0.88; P < 0.05), all-cause death (OR 0.86; 95% CI 0.79-0.93; P < 0.05) and the occurrence of renal dysfunction (OR 0.78; 95% CI 0.63-0.96; P < 0.05). The incidence of hypotension (OR 1.44; 95% CI 1.15-1.80; P < 0.05) and dizziness (OR 1.46; 95% CI 1.32-1.62; P < 0.05) was obviously increased in neprilysin-RAS inhibition compared with RAS inhibition. There were no significant differences in any adverse events, serious adverse events, myocardial ischemia, angioedema, hyperkalemia, fatigure, cough, gastrointestinal disorders and infections compared neprilysin-RAS inhibition with RAS inhibition alone.

CONCLUSIONS

The available evidence are supportive of the use of combined neprilysin and RAS inhibition in heart failure with close observation of blood pressure.