Dr Kieran Docherty paper is now online in the Lancet

SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials

MuthiahVaduganathanMD*Kieran FDochertyPhD*Brian LClaggettPhDa ProfPardeep SJhundPhDb ProfRudolf Ade BoerMDc ProfAdrian FHernandezMDd Silvio EInzucchiMDe ProfMikhail NKosiborodMDf ProfCarolyn S PLamMBBSdg ProfFelipeMartinezMDh ProfSanjiv JShahMDi Akshay SDesaiMDa ProfJohn J VMcMurrayMDb ProfScott DSolomonMD

Meta-analysis of SGLT2 inhibitors in HF is now online in the Lancet showing a consistent reduction in the risk of CV death and HF hospitalisation in a broad range of 21,947 patients across range of EF and in different care settings.

Summary

Background

SGLT2 inhibitors are strongly recommended in guidelines to treat patients with heart failure with reduced ejection fraction, but their clinical benefits at higher ejection fractions are less well established. Two large-scale trials, DELIVER and EMPEROR-Preserved, in heart failure with mildly reduced or preserved ejection fraction have been done, providing power to examine therapeutic effects on cardiovascular mortality and in patient subgroups when combined with the earlier trials in reduced ejection fraction.

Methods

We did a prespecified meta-analysis of DELIVER and EMPEROR-Preserved, and subsequently included trials that enrolled patients with reduced ejection fraction (DAPA-HF and EMPEROR-Reduced) and those admitted to hospital with worsening heart failure, irrespective of ejection fraction (SOLOIST-WHF). Using trial-level data with harmonised endpoint definitions, we did a fixed-effects meta-analysis to estimate the effect of SGLT2 inhibitors on various clinical endpoints in heart failure The primary endpoint for this meta-analysis was time from randomisation to the occurrence of the composite of cardiovascular death or hospitalisation for heart failure. We assessed heterogeneity in treatment effects for the primary endpoint across subgroups of interest. This study is registered with PROSPERO, CRD42022327527.

Results

Overall, 21 947 participants were included across five trials. Median follow-up time ranged from 9 months in SOLOIST-WHF to 2·3 years in DELIVER (table 1). Except for SOLOIST-WHF, which randomly assigned patients shortly after an episode of worsening heart failure, and DELIVER, in which a small proportion of patients (10%) were randomly assigned during or shortly after hospitalisation for heart failure, most patients included in this meta-analysis had chronic ambulatory heart failure.

 

Link to paper


First published: 30 August 2022