Abstract
Given the high risk of adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF), there is an urgent need for the initiation and titration of guideline-directed medical therapy (GDMT) that can reduce the risk of morbidity and mortality. Clinical practice guidelines are now emphasizing the need for early and rapid initiation of therapies that have cardiovascular benefit. Recognizing that there are many barriers to GDMT initiation and optimization, health care providers should aim to introduce the 4 pillars of quadruple therapy now recommended by most clinical practice guidelines: angiotensin receptor-neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors. A large proportion of patients with HFrEF do not have clinical contraindications to GDMT but are not treated with these therapies. Early initiation of low-dose combination therapy should be tolerated by most patients. However, patient-related factors such as hemodynamics, frailty, and laboratory values will need consideration for maximum tolerated GDMT. GDMT initiation in acute heart failure hospitalization represents another important avenue to improve use of GDMT. Finally, removal of therapies that do not have clear cardiovascular benefit should be considered to lower polypharmacy and reduce the risk of adverse side effects. Future prospective studies aimed at guiding optimal implementation of quadruple therapy are warranted to reduce morbidity and mortality in patients with HFrEF.