Komajda M, et al. - Researchers analyzed data from randomized controlled trials published between 1987 and 2017 to evaluate the relative effectiveness and incremental benefit of all recommended drug groups for the treatment of heart failure with reduced ejection fraction (HFrEF), including combinations. They searched biomedical databases to identify trials on angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), ivabradine (IVA), or angiotensin receptor–neprilysin inhibitors (ARNI). ARNI+BB + MRA and ACEI+BB + MRA + IVA were the most effective combinations, showing reductions in all-cause mortality of 62% and 59%, respectively. After analyzing 58 relevant trials and found that mortality and hospitalization outcomes in HFrEF have been progressively improved with the incremental use of combinations of disease-modifying therapies.