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

Abstract 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.