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

Abstract

BackgroundSacubitril/valsartan therapy reduced the risks of death and of hospitalization for heart failure (HF). HF and cardiac arrhythmias have shared physiological mechanisems. Therefore, sacubitril/valsartan may exhibit anti-arrhythmic properties in HF. The purpose of this study was to evaluate the effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of sudden cardiac death (SCD) in HF.MethodsThis meta-analysis was performed according to PRISMA guidelines. We searched PubMed and Embase (from inception up to 6 February 2022) to identify randomized control trials (RCTs) on the effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of SCD in HF. Primary outcomes were the occurrence of atrial arrhythmias, ventricular arrhythmias, and SCD. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model for meta-analysis.ResultsWe included 9 RCTs (published between 2012 and 2021) with 18,500 patients (9,244 sacubitril/valsartan vs. 9,256 active control). Enalapril and valsartan were used as active control in six and two studies, respectively. Follow-up ranged from 2 to 35 months. The cumulative occurrence of events was 76, 13, and 48 per 1,000 patient-years for atrial arrhythmias, ventricular arrhythmias and SCD, respectively. There was no significant association between sacubitril/valsartan therapy and the occurrence of atrial arrhythmias (RR 1.06; 95% CI: 0.97–1.17; P = 0.19) and ventricular arrhythmias (RR 0.86; 95% CI 0.68–1.10; P = 0.24). However, sacubitril/valsartan therapy significantly reduced the risk of SCD (RR 0.79; 95% CI 0.70–0.90; P = 0.03) compared with control.ConclusionNo association between sacubitril/valsartan therapy and the occurrence of atrial and ventricular arrhythmias was found, but sacubitril/valsartan therapy significantly reduced the risk of SCD.

Do Elderly Patients with Heart Failure and Reduced Ejection Fraction Benefit from Pharmacological Strategies for Prevention of Arrhythmic Events?

“…However, meta-analyses of randomized controlled trials have found conflicting results regarding the benefit of SV in the risk of arrhythmias. The most recent found no association between SV and the occurrence of atrial and VA, although SV reduced the risk of SCD [19]. This was an unexpected finding since most nonarrhythmic causes of SCD are related to ischemic heart disease [20].…”

The Role of Sacubitril/Valsartan and Gliflozins in Heart Failure with Reduced Ejection Fraction after Cardiac Resynchronization Therapy

“…In addition, S/V significantly reduced Sudden cardiac death (SCD) in patients eligible to implantable defibrillator therapy but without ICD 42 , but this effect was more pronounced after the first months of therapy 43 . The effectiveness of S/V on SCD reduction was confirmed in a meta-analysis of Liu et al 44 . These findings suggested that the underlying mechanism for the prevention of SCD is different from that of an ICD, probably related to the reverse remodeling.…”

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

“…Post hoc analyses of the PARADIGM-HF trial, investigating ARNi in HFrEF, showed a significant reduction in VA and the risk of SCD [ 59 , 60 ]. Liu et al [ 61 ] found in their meta-analyses that although ARNi did not affect the incidence of VA, it did significantly reduce the risk of SCD in heart failure patients. 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.…”