Abstract and Introduction
Sacubitril/valsartan is the first of a new class of drugs known as angiotensin receptor neprilysin inhibitors. In the pivotal PARADIGM-HF trial (Prospective Comparison of ARNi with ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure), published in 2014, 8442 patients with heart failure (HF) and reduced ejection fraction were randomized to receive either sacubitril/valsartan or enalapril. Patients in the sacubitril/valsartan group had a 20% relative risk reduction in the primary outcome cardiovascular death or HF hospitalization. Regarding the mode of death, most deaths in the study (1587; 80.9%) were because of cardiovascular factors, with sudden death being the most common cause of cardiovascular death (44.8%), followed by worsening HF (26.5%). The reduction in mortality with sacubitril/valsartan was similar for sudden death and pump failure (20% and 21% relative risk reduction, respectively), although notably with no effect on incident atrial fibrillation. These results are more compelling if we take into account that the vast majority of patients in the PARADIGM-HF trial received optimal guideline-based medical therapy with drugs that have already been shown to reduce overall mortality and sudden death; 93% of patients were taking β-blockers and 55% were taking a mineralocorticoid receptor antagonist. The reduction in sudden death with sacubitril/valsartan was independent of protection with implantable cardioverter defibrillators (ICDs), present in only 15% of enrolled patients.
Circulation. 2018;138(6):551-553. © 2018 American Heart Association, Inc.