Neurohormonal blockade and device-based therapies for heart failure (HF) greatly reduce morbidity and mortality. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated benefits in patients with HF across a broad range of phenotypes. In addition to SGLT2i, drugs targeting novel pathways have demonstrated benefit in heart failure with reduced ejection fraction (HFrEF). This review will provide an update on recent advances in the medical management of HF, highlighting the role of SGLT2i, vericiguat and omecamtiv mecarbil, along with new evidence on the benefit of rapid up-titration of guideline-directed medical therapy (GDMT) in patients with acute HF.

Dapagliflozin and empagliflozin reduce the risk of HF hospitalization and cardiovascular (CV) death in HF patients regardless of left ventricular ejection fraction (LVEF) and diabetes status. Their true mechanism of action in HF is not yet defined. Vericiguat, a stimulator of guanylate cyclase, and omecamtiv mecarbil, a cardiac myotrope, have shown benefit in HFrEF. Rapid up-titration of GDMT in patients hospitalized with HF is safe and results in improved clinical outcomes.

SGLT2i have earned their place as the fourth pillar of HF medical therapy alongside sacubitril-valsartan, evidence-based beta-blockers and mineralocorticoid receptor antagonists. They should be considered for the treatment of all symptomatic patients across the entire range of HF phenotypes, including patients hospitalized with HF. Vericiguat benefits high risk patients with worsening HF clinical profile. Most patients hospitalized with HF can be up-titrated to high doses of GDMT within weeks and this approach reduces the likelihood of adverse HF outcomes.