ACE and heart failure: Similar sex-based differences in HRQOL have also been observed in an analysis of two large randomized controlled trials including 15,415 patients with HFrEF from 55 countries, namely the prospective comparison of angiotensin receptor neprilysin inhibitor with an angiotensin converting enzyme-inhibitor to determine impact on global mortality and morbidity in heart failure (PARADIGM-HF) and Aliskiren trial to minimize outcomes in patients with heart failure (ATMOSPHERE).