Is there an antiarrhythmic benefit from switching to sacubitril/valsartan therapy? A systematic review and meta-analysis

Abstract

Abstract Background Sacubitril/valsartan through reverse structural remodeling and neurohormonal inhibition could play an antiarrhythmic role. Purpose This systematic review and meta-analysis was performed to explore the arrhythmiologic effects of switching patients with heart failure with reduced ejection fraction (HFrEF) from angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) to sacubitril/valsartan. Methods We searched major databases for studies comparing device-detected, incident atrial and ventricular arrhythmias in patients with HFrEF while on ACEi/ARBs versus while on sacubitril/valsartan. For pooling the primary outcome of interest, we calculated the risk difference (RD) with the corresponding 95% confidence interval (CI) in the probability of experiencing each arrhythmic event while on ACEi/ARBs and while on sacubitril/valsartan. A random effects (DerSimonian-Laird) model was adopted. Results We analyzed 4 eligible studies, resulting in 497 patients with a pooled mean age of 67.8±10.36. 64% had ischemic cardiomyopathy while 98% had either an implantable cardioverter defribrillator or a cardiac resynchronization therapy device. Main comorbidities were hypertension (68.7%) and dyslipidemia (59.6%). Almost all (96.3%) patients were treated with b-blockers and 23.7% were also receiving anti-arrhythmic drugs, mainly amiodarone. After switching to sacubitril/valsartan there was a trend towards reduced risk for sustained ventricular tachycardia/fibrillation and non-sustained ventricular tachycardias (RD: −0.04, 95% CI: −0.09–0.02, I2: 65.7% and −0.06, 95% CI: −0.19–0.07, I2: 85%; respectively). Meta-regression analysis showed that patients with ischemic cardiomyopathy experience greater benefit. Incident paroxysmal atrial fibrillation/tachycardia was significantly reduced (RD: −0.09 95% CI: −0.14 to −0.03, I2: 0%), while favorable effects were noticed for the risk of appropriate shock delivery and inadequate biventricular pacing (RD: −0.06, 95% CI: −0.09 to −0.03, I2: 0% and −0.06, 95% CI: −0.11 to 0.00, I2: 35.55%, respectively). All results seem to suffer from publication bias. Conclusion Limited data support that switching to sacubitril/valsartan seems to be associated with reduced risk for both ventricular and atrial arrhythmias. More studies are needed to clarify the potential anti-arrhythmic role of this drug. Whether patients with frequent arrhythmias or at high arrhythmic risk may benefit from early switch is a matter of further investigation. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2