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

Abstract

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. METHODSWe 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. RESULTSWe 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 6 9.8 years, with 77.3% male patients and a mean ejection fraction of 29.0% 6 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 5 .02), ventricular arrhythmias (OR 0.45, 95% CI 0.25-0.79; P 5 .005), and appropriate ICD therapy (OR 0.39, 95% CI 0.21-0.74; P 5 .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.

Efficacy and safety profile of angiotensin receptor neprilysin inhibitors in the management of heart failure: a systematic review and meta-analysis of randomized controlled trials

“…There was no significant difference in terms of arrhythmia endpoints (both atrial and ventricular arrhythmias) between sacubitril-valsartan and control group patients. Previous studies assessing these endpoints have also reported no difference between these groups [64,65]. Here also, the number of trials assessing these outcomes is limited and requires further large-scale trials to provide conclusive evidence on arrhythmia endpoints.…”

Effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of sudden cardiac death in heart failure: A meta-analysis of randomized controlled trials

“…Similar to previous meta-analysis, no significant association between sacubitril/valsartan and the occurrence of atrial arrhythmias, including AF, was observed. Another meta-analysis by Fernandes et al concluded that ARNI therapy was associated with lower SCD events and ventricular arrhythmias compared with control in HFrEF ( 8 ). However, the finding was underpowered limited to the included observational studies.…”

“…Two recent meta-analyses on the similar topic have been published ( 8 , 9 ). The meta-analysis by Fernandes et al found that ARNI therapy was associated with a reduction in SCD and ventricular arrhythmias compared with control in HF with reduced ejection fraction (HFrEF) ( 8 ). However, the role of sacubitril/valsartan in HF with preserved ejection fraction (HFpEF) remains unclear.…”

Anti-Arrhythmic Effects of Heart Failure Guideline-Directed Medical Therapy and Their Role in the Prevention of Sudden Cardiac Death: From Beta-Blockers to Sodium-Glucose Cotransporter 2 Inhibitors and Beyond

“…Another meta-analysis by Pozzi et al [ 62 ] demonstrated a significant reduction in the burden of VA and ICD shock when comparing ARNi to ACEi/ARB therapy. Fernandes et al [ 63 ] reported a significant reduction in SCD, VA, and appropriate ICD therapy with ARNi. Major studies and meta-analyses regarding the effect of ARNi on VA and SCD are summarized in Table 1 .…”