Sacubitril/valsartan versus angiotensin inhibitors and arrhythmia endpoints in heart failure with reduced ejection fraction

Amanda D.F. Fernandes, Gilson C. Fernandes, Caique M.P. Ternes, Rhanderson Cardoso, Sandra V. Chaparro, Jeffrey J. Goldberger

Research output: Contribution to journalArticlepeer-review


Background: Angiotensin receptor–neprilysin inhibitor (ARNI) therapy has been associated with improved survival for patients with symptomatic heart failure and reduced ejection fraction (HFrEF). Objectives: We performed a meta-analysis of arrhythmia endpoints from studies comparing ARNI with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with HFrEF to assess for incremental benefit. Methods: We searched PubMed, Embase, and Baseline study characteristics were collected and outcomes were sustained ventricular arrhythmias, atrial arrhythmias, appropriate implantable cardioverter-defibrillator (ICD) therapy, sudden cardiac death (SCD), and biventricular (BiV) pacing rate. Results: We included 9 studies, 4 randomized trials, and 5 observational studies (5589 patients on ARNI vs 5615 on ACEIs/ARBs). Follow-up ranged from 2 to 51 months. The mean age was 65.4 ± 9.8 years, with 77.3% male patients and a mean ejection fraction of 29.0% ± 7.6%. Ischemic cardiomyopathy was present in 62% of patients. In the ARNI group, there were less SCD (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63–0.96; P = .02), ventricular arrhythmias (OR 0.45, 95% CI 0.25–0.79; P = .005), and appropriate ICD therapy (OR 0.39, 95% CI 0.21–0.74; P = .004). Higher rates of BiV pacing were seen (mean difference 3.13, 95% CI 2.58–3.68; P < .00001) when compared with ACEIs/ARBs. No difference in atrial arrhythmias was seen. Conclusion: ARNI therapy provides incremental benefit with respect to ventricular tachyarrhythmias/SCD, which may, in part, explain improved outcomes in patients with HFrEF compared to ACEIs/ARBs. There was increased BiV pacing and decreased ICD therapy in the ARNI group.

Original languageEnglish (US)
Pages (from-to)724-732
Number of pages9
JournalHeart Rhythm O2
Issue number6
StatePublished - Dec 2021
Externally publishedYes


  • Angiotensin receptor antagonists
  • Antiarrhythmia agents
  • Heart failure
  • Sacubitril-valsartan
  • Sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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