Growing Mismatch Between Evidence Generation and Implementation in Heart Failure

Heart failure is a leading cause of morbidity and mortality globally. The natural history of heart failure with reduced ejection fraction (HFrEF) has been altered with the development of multiple therapeutic agents targeting maladaptive biologic pathways, including angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs), β-blockers, and mineralocorticoid antagonists (MRAs). While mechanistic studies overlapped, the landmark trials and their publications that led to the acceptance of these therapies as standards of care generally occurred sequentially.