Etiology and Treatment Response in Heart Failure with Reduced Ejection Fraction

The randomized, double-blind, industry-sponsored PARADIGM-HF trial (NEJM JW Cardiol Oct 2014 and N Engl J Med 2014; 371:993) reported the superiority of angiotensin receptor–neprilysin inhibitor (ARNI) treatment with sacubitril/valsartan to the angiotensin-converting-enzyme inhibitor enalapril in patients with chronic heart failure and heart failure with reduced ejection fraction (HFrEF). The current investigators reanalyzed these data to determine how the outcomes and treatment effect varied by the etiology of HFrEF.

The exclusion criteria for PARADIGM-HF included symptomatic hypotension or systolic blood pressure <100 mm Hg, estimated glomerular filtration rate <30 mL/minute/1.73 m², and potassium >5.2 mmol/L. Of the 8933 participants, 60%…