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Sodium–glucose cotransporter-2 (SGLT-2) inhibitors improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF; EF, ≤40%), and more recently, in those with mildly reduced or preserved ejection fraction (HFpEF; EF, >40%) (NEJM JW Gen Med Oct 1 2021 and N Engl J Med 2021; 385:1451; NEJM JW Cardiol Oct 2022 and N Engl J Med 2022 Aug 27; [e-pub]). In this meta-analysis, authors combined results from five randomized trials in which SGLT-2 inhibitors were compared with placebo. Outcomes were as follows:
Among patients with HFpEF, SGLT-2 inhibitors lowered the incidence of cardiovascular-related death or hospitalization compared with placebo (14.5% vs. 17.8%; number needed to treat, ≈30), including patients with EF of 50% to 59% (NNT, ≈30) and EF ≥60% (NNT, ≈40).
Among all patients with heart failure, SGLT-2 inhibitors lowered the incidence of cardiovascular-related death or hospitalization (15.8% vs. 19.7%; NNT, 25) and lowered all-cause mortality (13.8% vs. 14.8%; NNT, 92)
The composite outcome of cardiovascular-related death or hospitalization was consistent across various subgroups, including those categorized by age, sex, race, body-mass index, HF class, presence of atrial fibrillation, and use of other HF medications.
Vaduganathan M et al. SGLT-2 inhibitors in patients with heart failure: A comprehensive meta-analysis of five randomised controlled trials. Lancet 2022 Sep 3; 400:757. (https://doi.org/10.1016/S0140-6736(22)01429-5)
Comment
These data support use of SGLT-2 inhibitors in patients with both HFrEF and HFpEF. Because patients with substantial renal disease (usually, estimated glomerular filtration rate <30 mL/minute/1.73 m2) were excluded, the results don't apply to that patient population. Hopefully, SGLT-2 inhibitor costs will drop so that these highly efficacious medications can be applied equitably across patient populations with heart failure.