1113 EFFICACY OF SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION ACROSS DIFFERENT DEFINITIONS: A META-ANALYSIS OF PHASE 3 RANDOMIZED CONTROLLED TRIALS

Abstract

Abstract Background Sodium glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) in phase 3 randomized controlled trials (RCTs). However, a granular definition of HF was adopted only in the most recent RCTs (hereafter, HF RCTs). In earlier studies, which assessed cardiovascular (CV) outcomes in patients with type 2 diabetes (CV outcomes trials, CVOTs), HF status was assigned based on medical history. Methods We searched for RCTs evaluating SGLT2i vs placebo in HFpEF and published from inception to Aug. 31st 2022, irrespective of whether additional criteria were used to define HFpEF besides left ventricular ejection fraction ≥50%. Heterogeneity between studies was examined by the Cochran's Q test and Higgins and Thompsons’ I2 statistics. Risk ratios (RRs) with 95% confidence intervals (95%CI) and number needed to treat (NNT) were calculated with a random-effects model (moderate-to-high heterogeneity) or a Mantel-Haenszel fixed-effect model (low heterogeneity) using R 4.2.1. Results Seven RCTs were included in the meta-analysis: 3 HF RCTs (EMPEROR-Preserved, DELIVER, and SOLOIST-WHF) and 4 CVOTs (EMPA-REG OUTCOME, DECLARE-TIMI58, VERTIS-CV, and SCORED). The overall population included 14,644 patients, and the mean follow-up was 29.8±14.5 months (range: 9.0-50.4 months). The risk of the composite outcome of CV death or HF hospitalization (HFH) was significantly reduced by SLGT2i as compared with placebo (RR 0.75, 95%CI 0.63-0.89, I2=59.7%, NNT 19). The benefit was confirmed in HF RCTs (RR and 95%CI displayed in the Figure; I2=75.7%, NNT 13) and CVOTs (Figure; I2=56.9%, NNT 26). Based on the available data (i.e., only some of the selected studies), SGLT2i also had a positive effect on HFH (RR 0.81, 95%CI 0.73-0.90, I2=18.1%, NNT 45), which was maintained in both HF RCTs (Figure; I2=18.1%, NNT 37) and CVOTs (Figure; I2=0.0% and NNT 46, respectively). The effect on CV or all-cause death was neutral in all RCTs (RR 0.94, 95%CI 0.85-1.04, I2=36.0%; and RR 1.00, 95%CI 0.92-1.08, I2=0.0%, respectively), and in HF RCTs or CVOTs considered separately (Figure). Conclusions The efficacy of SGLT2i was consistent across RCTs with a stricter or simpler definition of HFpEF, supporting an extensive clinical use.