,36,37 The PARAGON-HF (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor with Angiotensin-receptor Blockers Global Outcomes in HF with Preserved Ejection Fraction) trial only included patients with a known intolerance of renin-angiotensin system inhibitors, and renal function was not accounted for in the CHARM (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity) analyses. Here, REN is linked to heart failure.