Primary prevention of heart failure with glucagon-like peptide-1 receptor agonist

Background Primary prevention of heart failure (HF) is important given its rising prevalence, associated disease burden, and healthcare expenditure.(1-3) Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cardiovascular outcomes and we sought to establish the effect of GLP-1 RAs on HF events across randomised clinical trials. Purpose To perform a meta-analysis of the effect of GLP-1 RA on HF events as reported in published RCTs, and investigate for changes by clinically relevant subgroups. Methods We performed a systematic review of RCTs that evaluated the relationship between GLP-1 RAs and the development of HF using Medline, Embase and Cochrane-controlled Trials Register from inception through 10 January 2024. For meta-analysis we included RCTs with at least 5 new-onset heart failure events in either arm or where HF hospitalisation was included in the primary or secondary outcome. Results of the HF hospitalisation are expressed as relative risk (RR) with 95% confidence interval (CI) between the intervention and control group for each study. A fixed-effect model was used to combine results from studies when I2<50% and random-effect model when I2>50%. Risk of bias was assessed using the Cochrane RoB2 tool. Results From 2568 unique records we included 9 RCTs and 49 648 participants in quantitative synthesis (mean age: 64.0 years, 35.2% female, 87.2% hypertensive [mean SBP 135 mmHg], 62.7% diabetic, mean BMI 32.9) (Table 1). All trials included diabetes and/or obesity, and three trials included heart failure with preserved ejection fraction (HFpEF). Overall, risk of bias was low (67% low, 33% medium) and driven by outcome measurement (55% medium) as HF events were not in the primary endpoint of 8 (89%) of studies. On meta-analysis, GLP-1 RA reduced incident HF hospitalisation by 21% (RR 0.79, 95% CI 0.70-0.88) across the included RCTs (Figure 1). When analysing only RCTs which required HFpEF for inclusion, GLP-1 RA had a strong protective effect in new-onset HF hospitalisation (RR 0.45, 95% CI 0.31-0.65) (Figure 1), and in RCTs incorporating diabetes mellitus and/or obesity but not necessarily HF, treatment with GLP1-RAs reduced HF hospitalisation by 16% (RR 0.84, 95% CI 0.74-0.94) (Figure 1). Conclusions In this meta-analysis treatment with GLP-1 RAs reduced incident HF hospitalisation across randomised clinical trial populations with diabetes and/or obesity, as well as in patients with obesity and HFpEF.