Heart failure (HF) is a leading global public health problem with more than 26 million prevalent cases around the world.1 The disease burden associated with HF has increasingly shifted from high-income countries to low- and middle-income countries due to population growth, aging, and increasing prevalence of HF risk factors.
Patients with HF with reduced ejection fraction (HFrEF) from low- and middle-income countries experience a higher 1-year mortality rate than those in high-income countries (20% vs 18%, respectively; adjusted hazard ratio [HR], 1.58 [95% CI, 1.41-1.78]) despite being almost 1 decade younger.2 Guideline-directed medical therapy (GDMT) consisting of β-blockers, renin angiotensin system blockers with neprilysin inhibitors, and mineralocorticoid receptor antagonists substantially reduces mortality among patients with HFrEF by an estimated 63% vs placebo (19.5% vs 50.0% mortality rate at 5 years) based on a network meta-analysis of 57 randomized trials.3 These medicines are among the most cost-effective interventions and are thus included as the “highest priority” interventions recommended by the Disease Control Priorities Project.4 Evidence has demonstrated a further 2.3% absolute risk reduction in all-cause mortality at 18 months from sodium-glucose cotransporter 2 (SGLT2) inhibitors (11.6% vs 13.9% for placebo; HR, 0.83 [95% CI, 0.71-0.97]), likely adding another drug class to the recommended regimens.5 Global inequalities in GDMT and HFrEF mortality may widen as use of SGLT2 inhibitors increases in high-income countries.