192 GLP1-RA AND HEART FAILURE-RELATED OUTCOMES IN PATIENTS WITH AND WITHOUT HISTORY OF HEART FAILURE: A SYSTEMATIC REVIEW AND METANALYSIS

Abstract

Abstract Background GLP1-receptor agonists (GLP1-ra) are recently developed anti-diabetic drugs which have shown promising results in phase-3 cardiovascular (CV) outcomes trials in diabetic patients, demonstrating a reduction in major adverse cardiovascular events (MACE) and, possibly, in heart failure (HF) hospitalizations. However, whether these medications improve such outcomes in patients with a history of HF remains unknown. Methods All randomized, placebo-controlled trials of GLP1-ra (and predefined/post-hoc analysis) reporting CV outcomes stratified by HF history were searched in Pubmed from inception to August 31st, 2022. The primary outcome was HF hospitalizations. Secondary outcomes included MACE, CV death and a composite of HF hospitalization and CV death. The analysis was performed after stratifying for HF history. Odds-ratio (OR) and 95% confidence interval (CIs) were used as effect estimated and calculated via a random-effects model. P for interaction between subgroups were calculated via meta-regression analysis and a level of p<0.10 was considered as significant. Results Data from 6 trials and a total of 40300 patients (n=20127 GLP1-ra group, n=20173 placebo group) were included. GLP1-ra reduced HF hospitalizations in patients without HF history (OR 0.71, 95% CI 0.51-0.99) but had neutral effect on those with previous HF (OR 1.04, 95% CI 0.88–1.22, p-interaction=0.089). CV death was also reduced by intervention only in the group without history of HF (OR 0.81, 95% CI 0.71–0.92), as well as the composite of HF hospitalizations and CV death (OR 0.80, 95% CI 0.72–0.90). Indeed, no difference between treatment arms was found in the HF group for CV death (OR 0.99, 95% CI 0.82–1.18, p-interaction=0.18) and the composite of HF hospitalization or CV death (OR 1.02 95%CI 0.89–1.18, p-interaction=0.073). MACE reduction was similar in patients with (OR 0.87 95% CI 0.72–1.06) and without HF history (OR 0.84 95% CI 0.76–0.93, p-interaction = 0.75). Conclusion GLP1-ra do not reduce HF hospitalization and CV death in patients with history of HF, as the benefit on cardiovascular outcomes provided by this anti-diabetic class of drugs seems to be mainly limited to patients without HF history. Future studies focused on HF patients are needed to confirm such findings and clarify the limited efficacy of GLP1-ra in this relevant group of patients.