Cardiovascular benefits of SGLT2 inhibitors in patients with heart failure: a meta-analysis of small and large randomized controlled trials

Saeed Shoar; Ahmed Ali Shah; Waleed Ikram; Najam Farooq; Agnes Udoh; Elsa Tabibzadeh; Soheila Khavandi; Siamak Khavandi

Cardiovascular benefits of SGLT2 inhibitors in patients with heart failure: a meta-analysis of small and large randomized controlled trials

Am J Cardiovasc Dis. 2021 Jun 15;11(3):262-272. eCollection 2021.

Authors

Saeed Shoar¹, Ahmed Ali Shah², Waleed Ikram³, Najam Farooq², Agnes Udoh⁴, Elsa Tabibzadeh⁵, Soheila Khavandi⁶, Siamak Khavandi⁷

Affiliations

¹ Department of Clinical Research, ScientificWriting Corp Houston, TX, USA.
² School of Medicine, Quaid-e-Azam Medical College Bahawalpur, Pakistan.
³ School of Medicine, Lahore Medical and Dental College Lahore, Pakistan.
⁴ School of Medicine, Madonna University Okija, Nigeria.
⁵ Department of Anesthesiology and Critical Care, Tabriz University of Medical Sciences Tabriz, Iran.
⁶ Department of Cardiology, Tabriz University of Medical Sciences Tabriz, Iran.
⁷ Department of Ophthalmology, Tabriz University of Medical Sciences Tabriz, Iran.

PMID: 34322297
PMCID: PMC8303041

Abstract

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown promise in improving cardiovascular outcome in patients with heart failure (HF) and diabetes mellitus (DM). Although these benefits have been confirmed by several meta-analyses, small studies have not been included into these pooled analyses.

Aim: Publication of recent RCTs prompted us to perform this updated meta-analysis to examine the consistency of favorable cardiovascular outcomes of SGLT2 inhibitors in HF patients by inclusion of clinical trials with small sample size.

Methods: We conducted a systematic review of the literature in PubMed/Medline and ClinicalTrials.gov to identify all RCTs investigating the benefits of SGLT2 inhibitors in patients with HF. The primary endpoint of this meta-analysis was to compare the cardiovascular death (CVD) and hospitalization for HF (HHF) between patients who received an SGLT2 inhibitor and those who received a placebo or a non-SGLT2 inhibitor. We used a risk difference (RD) and log hazard ratio (HR) to pool the reported difference across the included RCTs.

Results: A total of 12 RCTs encompassing 59,825 patients at different stages of HF and DM were included, 32,448 patients in the SGLT2 inhibitor group and 27,377 patients in the control group. A pooled analysis of RCTs, regardless of HF severity or DM status, showed a significantly reduced RD for CVD (RD =-0.01, 95% CI [-0.01, 0.00], P=0.01) and HHF (RD =-0.02, 95% CI [-0.03, -0.01], P=0.0005) in patients who received a SGLT2 inhibitor compared to those who did not. A sub-group analysis showed a significantly reduced RD for CVD (RD =-0.01, 95% CI [-0.02, 0.00], P=0.03) and HHF (RD =-0.02, 95% CI [-0.03, 0.00], P=0.01) in patients with DM who received SGLT2 inhibitors regardless of the severity of HF. Also, regardless of DM status, RD for HHF favored the use of SGLT2 inhibitor than the control medication (RD =-0.05, 95% CI [-0.06, -0.03], P<0.00001).

Conclusion: SGLT2 inhibitors have shown a promise in reducing CVD and HHF in patients with HF, regardless of ejection fraction or diabetes status.

Keywords: SGLT2 inhibitor; cardiovascular mortality; diabetes mellitus; heart failure; hospitalization for heart failure.