Angiotensin Receptor-Neprilysin Inhibitor Effects on Atherosclerotic Cardiovascular Disease Events: A Meta-Analysis of Randomized Controlled Trials

Am J Cardiol. 2023 Oct 15:205:259-268. doi: 10.1016/j.amjcard.2023.07.154. Epub 2023 Aug 22.

Abstract

Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) associated with a decreased risk of death and hospitalization for selected patients with heart failure (HF). However, its association with improved atherosclerotic cardiovascular disease (ASCVD) events remains unclear. We performed a meta-analysis to evaluate the association of ARNI with ASCVD events in patients with HF. We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for studies comparing ARNIs with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in terms of myocardial infarction, stroke, angina pectoris, peripheral artery disease, and the composite end point in patients with HF. A total of 8 randomized controlled trials were included, with 17,541 patients assigned to either the ARNI (8,764 patients) or ACEi/ARB (8,777 patients) groups. The incidence of composite end point (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.93 to 1.13, p = 0.63), myocardial infarction (RR 1.02, 95% CI 0.81 to 1.30, p = 0.85), angina pectoris (RR 0.96, 95% CI 0.80 to 1.17, p = 0.70), and stroke (RR 0.99, 95% CI 0.85 to 1.16, p = 0.93) were not statistically different between the ARNI and ACEi/ARB groups. However, ARNI was associated with a higher incidence of peripheral artery disease (RR 1.63, 95% CI 1.05 to 2.52, p = 0.03). In conclusion, this meta-analysis found no association between ARNI therapy and improved ASCVD events in patients with HF.

Keywords: ARNI; ASCVD; atherosclerosis; sacubitril-valsartan.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Angina Pectoris
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents
  • Antiviral Agents
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / epidemiology
  • Cardiovascular Diseases* / epidemiology
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Humans
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / epidemiology
  • Neprilysin
  • Peripheral Arterial Disease*
  • Randomized Controlled Trials as Topic
  • Stroke*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists
  • Neprilysin
  • Antihypertensive Agents
  • Antiviral Agents