Sodium–glucose co‐transporter 2 inhibitors for heart failure: clinical trial efficacy and clinical practice effectiveness

Abstract

Recent randomized controlled trials have established sodium– glucose co-transporter 2 (SGLT-2) inhibitors as a new cornerstone therapy for patients with heart failure (HF) with reduced ejection fraction (HFrEF).1 These trials showed SGLT-2 inhibitors to significantly reduce cardiovascular mortality and HF hospitalization, with consistent efficacy regardless of diabetes status.1 These benefits for traditional cardiovascular outcomes were combined with improvements in patient-reported quality of life, improvements in New York Heart Association functional class, and less progression of renal disease.1 Moreover, benefits with respect to clinical events and quality of life were seen within days to weeks of initiation, suggesting that any delay in therapy exposes patients to substantial excess risk.2,3 Combined with the other pillars of comprehensive disease-modifying quadruple therapy [angiotensin receptor–neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA)], use of SGLT-2 inhibitors may reduce risk of mortality for patients with HFrEF by 73% over 2 years.4 However, as we laud SGLT-2 inhibitors as a major therapeutic advance, history has taught us that strong efficacy and safety in clinical trials are unfortunately not enough to ensure robust real-world use of life-saving therapies for HFrEF. For example, in contemporary European and US clinical practice, among patients eligible for therapy, high proportions do not receive a renin-angiotensin system inhibitor, beta-blocker, or MRA, or receive therapies at sub-target doses.5–7 Challenges with implementation may be particularly pronounced for newer therapies, where early adoption is generally slow and varied. For example, in the first year after