META-ANALYSIS OF DEDICATED HEART FAILURE TRIALS EVALUATING THE EFFECT OF SACUBITRIL/VALSARTAN ON MAJOR CARDIAC RHYTHM DISORDERS

Abstract

Objective: The important role of major cardiac rhythm disorders in the prognosis of subjects with heart failure (HF) has been discussed extensively. Sacubitril/valsartan has revolutionized treatment strategy for patients with HF with reduced left ventricular ejection fraction (HFrEF), while it is cardiovascular safe -but not efficacious- in patients with HF with preserved ejection fraction (HFpEF). Anti-arrhythmogenic effect of sacubitril/valsartan has been demonstrated in several, recent experimental studies, however the clinical implications of that observations remain largely unknown. Design and method: We sought to determine the effect of sacubitril/valsartan compared to active comparator on major cardiac rhythm disorders in patients with HF, pooling data from the dedicated HF outcome trials. We evaluated the following outcomes of interest: atrial fibrillation, atrial flutter, ventricular tachycardia, ventricular fibrillation and cardiac arrest. The latter outcome was assessed in the light of recent evidence that arrhythmias account for almost 7% of cardiac arrest cases, both in in-hospital and out-of-hospital settings. Results: We pooled data from 3 trials in a total of 14,128 enrolled subjects with HF regardless of LVEF, assigned either to sacubitril/valsartan or valsartan.Sacubitril/valsartan compared to valsartan alone did not result in a significant risk reduction for atrial fibrillation (RR = 1.05, 95% CI; 0.89–1.24, I2 = 0%), atrial flutter (RR = 1.01, 95% CI; 0.55–1.86, I2 = 34%), ventricular tachycardia (RR = 0.92, 95% CI; 0.53–1.58, I2 = 32%) and ventricular fibrillation (RR = 0.79, 95% CI; 0.47–1.32, I2 = 0%). However, we demonstrated that sacubitril/valsartan compared to valsartan conferred a significant risk reduction in cardiac arrest by 47% (RR = 0.53, 95% CI; 0.38–0.76, I2 = 0%). Conclusions: Therefore, despite the cardiovascular efficacy and safety of sacubitril/valsartan among patients with HF, and its established role in the treatment of patients with HFrEF, it does not prevent major cardiac arrhythmias. However, its preventive role against cardiac arrest is of utmost importance and should be assessed in future randomized controlled trials as a surrogate outcome.