Evaluating the safety and tolerability of sacubitril/valsartan

Abstract

Sacubitril/valsartan is recommended in clinical practice to reduce morbidity and mortality in patients with chronic symptomatic heart failure with reduced ejection fraction (HFrEF). The PARADIGM-HF trial showed that sacubitril/valsartan was superior to enalapril in reducing the risk of death and hospitalisation in patients with chronic heart failure secondary to left ventricular systolic dysfunction. Findings from further trials showed improvement in cardiac remodeling with sacubitril/valsartan in patients with HFrEF. The TITRATION study tested the tolerability of initiation and up-titration of sacubitril/valsartan and demonstrated that hypotension and hyperkalaemia were the most common adverse events recorded, but were most often not severe enough to require treatment discontinuation. Due to safety concerns, development of a protocol is required for patients on sacubitril/valsartan to reach the target dose with gradual dose titration and with appropriate follow-up to improve tolerability and allowing patients to attain expected treatment benefits.