title: Renin-angiotensin-aldosterone system blockers for heart failure with reduced ejection fraction or left ventricular dysfunction: Network meta-analysis.
abstract: BACKGROUND
  Renin-angiotensin-aldosterone system (RAAS) blockers are effective therapies for heart failure and reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVD). We aimed to assess the efficacy and safety of RAAS blockers in these patients.
  
  
  METHODS
  We searched MEDLINE, EMBASE, and Cochrane Library in May 2015. Twenty-one double-blind randomized controlled trials (RCTs) with 69,229 patients were included this network meta-analysis.
  
  
  RESULTS
  Compared with placebo, an angiotensin receptor-neprilysin inhibitor (ARNI) had the highest probability of reducing all-cause mortality (odds ratio [OR]=0.67, 95% credible interval [CrI]: 0.48-0.86), followed by an aldosterone receptor antagonist (ARA, OR=0.74, 95% CrI: 0.62-0.88) and an angiotensin-converting enzyme inhibitor (ACEI, OR=0.80, 95% CrI: 0.71-0.89). The most efficacious therapy for preventing heart failure hospitalization was ARNI (OR=0.55, 95% CrI: 0.40-0.71), followed by combination therapy with an angiotensin II receptor blocker (ARB) plus an ACEI (OR=0.61, 95% CrI: 0.49-0.75), then an ACEI alone (OR=0.69, 95% CrI: 0.61-0.77). Sensitivity analysis restricted to nine RCTs with a high background use of ACEI and/or ARB (>80%) indicated that adding an ARA to current standard therapy significantly reduced mortality (OR=0.73, 95% CrI: 0.51-0.95) and hospitalization risk (OR=0.67, 95% CrI: 0.47-0.87), but did not significantly increase the discontinuation risk (OR=1.29, 95% CrI: 0.83-2.31).
  
  
  CONCLUSIONS
  ARNI has the highest probability of being the most efficacious therapy for HFrEF in reducing death and hospitalization for heart failure. ARA has the most favorable benefit-risk profile as an adjunct to background ACEI and/or ARB therapy.
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China. Electronic address: xiewuxiang@163.com.
authors.forename: Wuxiang
authors.initials: W
authors.lastname: Xie
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Department of Biostatistics, Columbia University, New York, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Psychiatry, University of Rochester Medical Center, New York, USA.
authors.forename: Baoliang
authors.initials: B
authors.lastname: Zhong
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UK.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013318:Stroke Volume / Q000187:drug effects* / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: Heart failure and reduced ejection fraction; Left ventricular dysfunction; Network meta-analysis; Renin–angiotensin–aldosterone system