Sacubitril/Valsartan Versus Angiotensin Inhibitors and Arrhythmia Endpoints in Heart Failure with Reduced Ejection Fraction

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 ClinicalTrials.gov. 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 (5,589 patients on ARNI vs 5,615 on ACEIs/ARBs). Follow-up ranged from 2 to 51 months. The mean age was 65.4 {±} 9.8 years-old, with 77.3% males and a mean EF of 29.0{±}7.6%. Ischemic cardiomyopathy was present in 62% of patients. In the ARNI group, there were less SCD (OR FE 0.78, 95%CI 0.63-0.96; p = 0.02), ventricular arrhythmias (OR FE 0.45, 95%CI 0.25- 0.79; p = 0.005) and appropriate ICD therapy (OR FE 0.39, 95% CI 0.21-0.74; p = 0.004). Higher rates of BiV pacing were seen (MD 3.13, 95% CI 2.58-3.68; p < 0.00001) when compared with ACEIs/ABRs. No difference in atrial arrhythmias was seen. Conclusions: 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.