Cardiovascular Outcomes with SGLT-2 inhibitors in patients with heart failure with or without type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials

Abstract

Background and aims: We conducted a systematic review and meta-analysis of all the randomized controlled trials (RCTs) with SGLT-2 inhibitors (SGLT-2i) in patients with known heart failure (HF) with or without type 2 diabetes (T2DM), that have studied the outcomes of cardiovascular (CV) death, hospitalization due to HF (HHF), and composite of CV death or HHF.

Methods: A systematic search in PubMed, Embase and Cochrane Library database were made up till November 20, 2020 using specific keywords. RCTs that qualified underwent a meta-analysis by applying the inverse variance-weighted averages of pooled logarithmic hazard ratio (HR) using both random- and fixed-effects model.

Results: This meta-analysis of 9 RCTs (N = 19,741) have found a significant 26% relative risk reduction in composite of CV death or HHF (HR 0.74; 95% CI, 0.69-0.79; p < 0.001) with SGLT-2i in patients with HF. The meta-analysis of 8 RCTs (N = 16,460) also showed a significant reduction in CV death (HR 0.86; 95% CI, 0.78-0.95; p = 0.003) and HHF (HR 0.68; 95% CI, 0.62-0.74; p < 0.001) outcomes with SGLT-2i in patients with HF. Subgroup analysis stratified on baseline ejection fraction (EF) showed a similar benefit in the composite of CV death or HHF in patients with HF with reduced EF (HFrEF) or preserved EF (HFpEF).

Conclusions: SGLT-2i significantly reduces the composite of CV death or HHF, CV death, and HHF in patients with HF. Although subgroup analysis suggested an insignificant P_heterogenity for these outcomes irrespective of the types of HF, however, reduction in both CV death and HHF were more pronounced in patients with HFrEF.

Keywords: Cardiovascular death; Heart failure hospitalization; Meta-analysis; SGLT-2 inhibitors; Systematic review; Type 2 diabetes.