Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, China.
Department of Cardiology, Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing 100044, China.
Int J Cardiol. 2019 Oct 15;293:159-164. doi: 10.1016/j.ijcard.2019.05.048. Epub 2019 May 23.
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.
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.
Medline, the Cochrane Library and Clinicaltrials.gov were searched for randomized controlled trials (RCTs). Twelve studies covering 21,212 patients were eligible for inclusion.
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.
The available evidence are supportive of the use of combined neprilysin and RAS inhibition in heart failure with close observation of blood pressure.
安全性问题使医生不愿意开肾素-血管紧张素系统（RAS）抑制剂。本荟萃分析旨在评估联合应用 Neprilysin 和 RAS 抑制剂治疗心力衰竭的疗效和安全性。
联合 Neprilysin 和 RAS 抑制剂可减少心力衰竭住院和心血管死亡。然而，临床试验中 Neprilysin-RAS 抑制剂的不良反应仍存在争议。
检索 Medline、Cochrane 图书馆和 Clinicaltrials.gov 以获取随机对照试验（RCT）。纳入了 12 项涵盖 21212 名患者的研究。
与 RAS 抑制相比，Neprilysin-RAS 抑制可显著降低心力衰竭死亡率[比值比（OR）0.84；95%置信区间（CI）0.78-0.91；P<0.05]、心血管死亡（OR 0.78；95%CI 0.69-0.88；P<0.05）、全因死亡（OR 0.86；95%CI 0.79-0.93；P<0.05）和肾功能障碍的发生（OR 0.78；95%CI 0.63-0.96；P<0.05）。与 RAS 抑制相比，Neprilysin-RAS 抑制的低血压（OR 1.44；95%CI 1.15-1.80；P<0.05）和头晕（OR 1.46；95%CI 1.32-1.62；P<0.05）发生率明显增加。与单独使用 RAS 抑制剂相比，Neprilysin-RAS 抑制剂在任何不良反应、严重不良反应、心肌缺血、血管性水肿、高钾血症、疲劳、咳嗽、胃肠道疾病和感染方面均无显著差异。
现有证据支持在密切监测血压的情况下，心力衰竭中联合应用 Neprilysin 和 RAS 抑制剂。
