Introduction and Objective: Cardiovascular outcomes trials (CVOTs) with GLP-1 receptor agonists (GLP-1RAs) have been performed in patients with atherosclerotic cardiovascular disease (ASCVD) or with high risk only at baseline. Meta-analyses suggest no significantly different hazard ratio for major adverse cardiovascular events (MACE) comparing active vs. placebo treatment. Absolute risk reductions have not been compared. Methods: CVOTs reporting results for MACE for subgroups with and without ASCVD at baseline were analysed (LEADER, SUSTAIN-6, EXSCEL, REWIND, PIONEER-6, AMPLITUDE-O, SOUL). The percentage of participants experiencing MACE events was calculated for placebo and active treatment, and the difference represented absolute risk reduction. For all CVOTs, results were pooled for participants with (ASCVD+) or without ASCVD (ASCVD-) at baseline, and compared. All data were normalized to a 3-year period of observation assuming linear accrual of MACE endpoints. Results: 13,409 patients (or 25.8 %) had no ASCVD at baseline, and 38,642 had ASCVD. Relative risk reductions (odds ratios) were not significantly different between both subpopulations (ASCVD+: 0.83 95 % CI: 0.78-0.88; ASCVD-: 0.89 95 % CI: 0.79-1.00). However, absolute risk reductions were significantly greater for ASCVD+ patients (2.12 95 % CI 1.96-2.27 %) than for ASCVD-patients (0.92 95 % CI 0.70-1.14 %). Consecutively, the numbers-needed-to-treat for MACE reduction were significantly lower in ASCVD+ patients (47 95% CI 44-51 than in ASCVD-patients (109 95% CI 88-144). The risk for MACE with placebo treatment was higher (4.7 95 % CI 4.5-4.9) in ASCVD+ than in ASCVD-patients (3.0 95% CI 2.8-3.2 per 100 PYO). Conclusion: Our results confirm that relative risk reduction is not significantly different between patients with or without ASCVD at baseline, but the absolute risk reductions were significantly higher, and the number needed-to-treat was significantly lower in those with ASCVD at baseline. Disclosure M.A. Nauck: Advisory Panel; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Pfizer Inc., Regor. Consultant; Current; Structure Therapy. Speaker's Bureau; Current; Eli Lilly and Company, Novo Nordisk, Medscape, Medical Learning Institute. Advisory Panel; Current; Sun Pharmaceutical Industries Ltd. B. Stratmann: Research Support; Current; Amgen Inc. Research Support; Ended; Applied Therapeutics. Research Support; Current; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Eli Lilly and Company, Roche Diabetes Care. S. Reger-Tan: Advisory Panel; Current; Abbott Diabetes. Consultant; Current; Abbott Diabetes. Advisory Panel; Current; Bayer AG. Other - Lectures; Current; Boehringer Ingelheim International GmbH. Research Support; Current; Boehringer Ingelheim International GmbH. Advisory Panel; Current; Dexcom, Inc. Research Support; Current; Eli Lilly and Company. Other - Lectures; Current; Eli Lilly and Company. Advisory Panel; Current; Novo Nordisk. Research Support; Current; Novo Nordisk. Other - Lectures; Current; Novo Nordisk. Advisory Panel; Current; Insulet Corporation. Research Support; Current; AstraZeneca, Amgen Inc., Vertex Pharmaceuticals Incorporated. Other - Lectures; Current; Abbott Diabetes. Research Support; Current; Novartis AG, Bayer AG, Roche Diabetes Care. Other - Lectures; Ended; Bayer AG, Berlin-Chemie AG, Sanofi-Aventis Deutschland GmbH. Consultant; Current; Medtronic. Research Support; Current; Applied Therapeutics. Y. Lee-Barkey: Speaker's Bureau; Current; AstraZeneca. Research Support; Current; AstraZeneca, Amgen Inc. Speaker's Bureau; Current; Amgen Inc. Research Support; Ended; Applied Therapeutics. Speaker's Bureau; Ended; Boehringer Ingelheim International GmbH. Research Support; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novartis AG, Novo Nordisk. Advisory Panel; Current; Sanofi.
NAUCK et al. (Fri,) studied this question.