Effect of sacubitril-valsartan on the incidence of atrial fibrillation: A meta-analysis

J Cardiovasc Electrophysiol. 2023 Apr;34(4):1037-1042. doi: 10.1111/jce.15880. Epub 2023 Mar 16.


Introduction: Sacubitril/valsartan reduces all-cause mortality in heart failure (HF) patients compared to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). ACEIs/ARBs have been shown to decrease the incidence of atrial fibrillation (AF). We hypothesized sacubitril-valsartan decreases the incidence of AF compared to ACEis/ARBs.

Methods: Clinicaltrials.gov was searched for trials by terms sacubitril/valsartan, entresto, sacubitril, valsartan. Randomized controlled human trials of sacubitril/valsartan reporting AF were included. Data were extracted independently by two reviewers. Data was pooled using a random effect model. Publication bias was evaluated by funnel plots.

Results: A total of 11 trials including 11,458 patients on sacubitril/valsartan and 10,128 patients on ACEI/ARBs were identified. A total of 284 AF events were reported in the sacubitril/valsartan group compared to 256 AF events in ACEIs/ARBs. Patients on sacubitril/valsartan were as likely as patients on ACEIs/ARBs to develop AF (pooled odds ratio [OR] = 1.091, 95% confidence interval [CI] = 0.917-1.298, p = .324). Six atrial flutter (AFl) events were reported in six trials; 48 out of 9165 patients in the sacubitril/valsartan group developed AFl compared to 46 out of 8759 in ACEi/ARBs group. There was no difference in AFl risk between the two groups (pooled OR = 1.028, 95% CI = 0.681-1.553, p = .894). Finally, sacubitril/valsartan did not reduce the risk of atrial arrhythmias (AF + AFl) compared to ACEi/ARBs (pooled OR = 1.081, 95% CI = 0.922-1.269, p = .337).

Conclusion: Although sacubitril/valsartan reduces mortality compared to ACEIs/ARBs in HF patients, they do not reduce AF risk compared to these drugs.

Keywords: angiotensin receptor blockers; angiotensin receptor neprilysin inhibitors; angiotensin-converting enzyme inhibitors; atrial fibrillation; sacubitril-valsartan.

Publication types

  • Meta-Analysis

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Atrial Fibrillation* / epidemiology
  • Heart Failure*
  • Humans
  • Incidence
  • Valsartan


  • sacubitril and valsartan sodium hydrate drug combination
  • Angiotensin-Converting Enzyme Inhibitors
  • sacubitril
  • Angiotensin Receptor Antagonists
  • Valsartan