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Effect of SGLT-2 inhibitors on cardiovascular outcomes in heart failure patients: A meta-analysis of randomized controlled trials

Published:April 03, 2021DOI:https://doi.org/10.1016/j.ejim.2021.03.020

      Highlights

      • SGLT-2i have remarkable cardioprotective effects in a broad range of HF patient.
      • Risk of CVD/HHF in HF patients was significant decreased by 23% in SGLT-2i group.
      • Beneficial effects were robust and unchanged when stratified by T2DM status.
      • Safety profiles were generally comparable between SGLT-2i and placebo groups.

      Abstract

      Background

      To investigate the overall effect of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on cardiovascular outcomes in a broad spectrum of heart failure (HF) patients, and further stratified by status of ejection fraction and diabetes mellitus.

      Methods

      Electronic databases were searched to identify randomized controlled trials that compared SGLT-2i with placebo in patients with HF. Efficacy outcomes included the composite of cardiovascular death (CVD) or hospitalization for heart failure (HHF), individual CVD, individual HHF, and all-cause mortality (ACM).

      Results

      A total of 8 large trials comprising 16,460 HF patients were enrolled. Pooled data demonstrated that SGLT-2i significantly reduced the risk for primary composite outcome (CVD or HHF) by 23% (HR: 0.77, 95% CI: 0.72–0.82) in HF patients. Use of SGLT-2i was associated with a statistically significant 32% reduction in HHF (HR: 0.68, 95% CI: 0.62–0.75), a 15% reduction in CVD (HR: 0.85, 95% CI: 0.76–0.94) and a 16% reduction in ACM (HR: 0.84, 95% CI: 0.77–0.92). Sensitivity analyses using Mantel-Haenszel method displayed consistent results. Subgroup analyses demonstrated that SGLT-2i were robustly effective in HFrEF subgroup as well as in HF with absence/presence of T2DM, and displayed a strong trend to be effective in HFpEF. Safety analysis demonstrated SGLT-2i group had a lower proportion of serious adverse events than placebo group (RR 0.89, 95% CI: 0.86–0.93).

      Conclusions

      Compared with placebo, SGLT-2 inhibitors have remarkable cardiovascular benefits in a broad range of HF patients. Beneficial effects were robust in HF patients regardless of T2DM status, and a strong trend to be effective in HFpEF.

      Keywords

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      Linked Article

      • SGLT2 inhibitors: Do we need other evidences?
        European Journal of Internal MedicineVol. 87
        • Preview
          The five cardiovascular outcome trials (CVOT) conducted in patients with type 2 diabetes mellitus so far have shown that renal sodium-glucose cotransporters two inhibitors (SGLT2i) are cardiovascular (CV) safe [1–5]. This finding paved the way for their use in patients with type 2, and even type 1, diabetes to reduce the HbA1c by 0.5 to 1.5%, depending on the baseline values. However, CVOT demonstrated a CV benefits of SGLT2i well beyond their antidiabetic effect.
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