Many eligible patients with heart failure (HF) with reduced ejection fraction (HFrEF) never receive therapies shown to extend survival or receive them with much delay.^1,2 Multiple recent successes in pharmacotherapy for HFrEF provide impetus for embracing change in HFrEF treatment in clinical practice. Quadruple therapy with an angiotensin receptor–neprilsyin inhibitor (ARNI), evidence-based β-blocker, mineralocorticoid receptor antagonist (MRA), and sodium glucose cotransporter 2 inhibitor (SGLT2i) may reduce risk of death by 73% over 2 years.³ Herein, we present the case for simultaneous or rapid sequence initiation of these 4 lifesaving therapies (Figure).

Not only do these 4 therapies extend survival, but for each, event curves separate early, with large relative and absolute reductions in mortality and hospitalization within days to weeks. Most recently, empagliflozin demonstrated a significant 58% relative reduction in death, hospitalization for HF, or an emergency or urgent HF visit at 12 days after initiation.⁴ Similar results were seen for dapagliflozin⁵ and sotagliflozin.⁶ Delaying therapy even a few weeks comes at the cost of preventable deaths and hospitalizations. While these clinical benefits are relevant for all eligible patients, considering that approximately 1 in 4 US patients hospitalized for HF die or are rehospitalized within 30 days of discharge,⁷ sending patients home from the hospital with quadruple therapy as tolerated should be a particularly high priority.