Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), was proven to be superior to angiotensin-converting enzyme inhibitor (ACEI), with significant reduction in all-cause mortality and composite outcome of heart failure hospitalization or cardiovascular mortality, in patients with heart failure with reduced ejection fraction (HFrEF) in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial (1). This evidence concerns the gene ACE and heart failure.