SGLT2 inhibitors decrease cardiovascular death and heart failure hospitalizations in patients with heart failure: A systematic review and meta-analysis

Abstract

Background: SodiumÀglucose cotransporter 2 (SGLT2) inhibitors reduce the composite of heart failure (HF) hospitalizations or cardiovascular mortality among patients with HF. However, the efficacy of SGLT2 inhibitors in secondary endpoints of randomized trials and in subgroups of HF patients is not well known. Methods: We performed a systematic review and meta-analysis of placebo-controlled, randomized trials of SGLT2 inhibitors in patients with HF. PubMed, Embase, and Cochrane databases were searched for trials published up to January 21, 2021. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Hazard ratios (HRs) with 95% CI were pooled across trials. The primary endpoints of interest were all-cause and cardiovascular mortality. Results: Out of 3969 database results, 15 randomized trials and 20,241 patients were included; 10,594 (52¢3%) received SGLT2 inhibitors. All-cause mortality (HR 0¢86; 95% CI 0¢79À0¢94; p = 0¢0007; I 2 =0%) and cardiovascular mortality (HR 0¢86; 95% CI 0¢78À0¢96; p = 0¢006; I 2 =0%) were significantly lower in patients treated with SGLT2 inhibitors compared with placebo. The composite of cardiovascular mortality, HF hospitalizations, or urgent visits for HF was significantly reduced with SGLT2 inhibitors in all the following subgroups: male, female, age < 65, age 65, race À Black and White, estimated glomerular filtration rate (eGFR) <60, eGFR 60, New York Heart Association (NYHA) class II, NYHA III, and HF with preserved ejection fraction. Interpretation: In patients with HF, SGLT2 inhibitors significantly reduce all-cause and cardiovascular mortality compared with placebo. In addition, the composite of cardiovascular mortality or HF hospitalizations/ urgent visits is reduced with SGLT2 inhibitors across subgroups of sex, age, race, eGFR, HF functional class, and ejection fraction.

Dapagliflozin Impact on the Exercise Capacity of Non-Diabetic Heart Failure with Reduced Ejection Fraction Patients

“…Addition of SGLT2i to triple neurohormonal blockade therapy was associated with an estimated 13% reduction in overall mortality risk and a 14% reduction in CV mortality risk, accompanied by a 26% reduction in the combined relative risk of 26% CV mortality/first hospitalization for HF and 25% risk of CV mortality/recurrent hospitalization for HF [ 7 ]. This effect was consistent across different subgroups, namely New York Heart Association (NYHA) functional class, ejection fraction, renal function, presence of diabetes and baseline HF risk models [ 8 ].…”

“…The finding that SGLT2i reduced the risk of a first hospitalization for HF in patients with type 2 diabetes raised a new perspective for the care of HF patients [ 2 , 3 , 4 ]. Accumulating evidence from other RCTs, whose results were published after this study’s design, established a class effect on HF for SLT2i [ 8 ]. Furthermore, with the published results of EMPEROR-Preserved and SOLOIST-WHF trials, there is a growing body of evidence suggesting a beneficial effect of SGLT2i on heart failure events across the spectrum of LVEF [ 23 , 24 , 25 ].…”

Medical Therapies for Heart Failure in Hypoplastic Left Heart Syndrome

“…In a systematic meta-analysis, SGLT2i also appear to significantly reduce systolic and diastolic blood pressure [ 91 ]. Additionally, a second meta-analysis suggests reduced cardiovascular mortality and HF hospitalizations among adult HF patients in multiple cardiovascular outcome trials, even in the absence of T2D reviewed in [ 92 ]. Interestingly, the cardiac benefits seen in response to SGLT2i therapy might be partly explained by their effects on ion handling and metabolism of cardiac myocytes reviewed in [ 84 ].…”

Women and Diabetes: Preventing Heart Disease in a New Era of Therapies

“…Recent meta-analyses reported that SGLT2is not only reduce the risk of new-onset HF, hospitalisations for HF (HHF), protect from worsening renal function and end-stage renal disease (ESRD), but also reduce all-cause as well as CV death, with similar benefits in patients in primary or secondary prevention and with and without a history of HF. 10,11 Moreover, these meta-analyses report a reduction in MI by 25% compared to OMT -with a specific benefit regarding this endpoint proved by canagliflozin in the CREDENCE trial and sotagliflozin in the SCORED trial -without apparent benefits in stroke reduction, except for the recent SCORED trial, requiring further investigation to better understand the underlying mechanisms providing these benefits. 9 The magnitude of benefits varied according to baseline CV risk and renal function.…”