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.