MACE risk and effect of semaglutide in patients with overweight or obesity and previous CABG

A prespecified analysis of SELECT trial among ASCVD patients with BMI ≥27 kg/m² but no diabetes showed a history of CABG was associated with higher risks of MACE and all-cause mortality. Semaglutide reduced these risks compared with placebo.

This summary is based on the publication of Verma S, Emerson S, Plutzky J, et al. - Semaglutide Improves Cardiovascular Outcomes in Patients With History of Coronary Artery Bypass Graft and Obesity. J Am Coll Cardiol. 2024 Nov 18:S0735-1097(24)10422-6 Online ahead of print]. doi: 10.1016/j.jacc.2024.11.008

Introduction and methods

Background

In patients with overweight or obesity undergoing CABG, their body weight may have a positive effect on postoperative outcomes (“obesity paradox”) [1,2]. However, data from RCTs evaluating CV outcomes after CABG in patients with obesity but no diabetes are limited. In addition, the effects of GLP-1RA treatment and/or weight loss on clinical outcomes in this population remain unknown.

In the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity) trial, the GLP-1RA semaglutide reduced the risk of MACE compared with placebo in patients with overweight or obesity but no diabetes [3,4].

Aim of the study

In a prespecified analysis of the SELECT trial, the authors evaluated the risk of MACE in patients with overweight or obesity and previous CABG and the treatment effect of semaglutide on MACE.

Methods

The SELECT trial was a multicenter, double-blind, placebo-controlled, parallel-group, event-driven phase 3 RCT in which 17,604 patients (aged ≥45 years) with ASCVD (i.e., previous MI, stroke, or symptomatic peripheral artery disease) and BMI ≥27 kg/m² but no diabetes were randomized to subcutaneous semaglutide 2.4 mg once weekly or placebo. Mean ± SD follow-up duration was 39.8 ± 9.4 months. Of the total study population, 2057 patients (11.7%) had a history of CABG.

Outcome

The study’s primary endpoint was the time to first MACE, defined as a composite outcome of CV death, nonfatal MI, or nonfatal stroke.

Main results

Association between CABG history and MACE risk

• In the placebo group, patients with a history of CABG had a higher risk of the primary endpoint than those with no previous CABG (HR: 1.46; 95%CI: 1.19–1.78; P=0.0002).
• Patients with a history of CABG also showed increased risks of CV death (HR: 1.79; 95%CI: 1.30–2.41; P=0.0002), nonfatal MI (HR: 1.58; 95%CI: 1.18–2.10; P=0.0016), and all-cause mortality (HR: 1.57; 95%CI: 1.22–1.98; P=0.0002) compared with non-CABG patients but not nonfatal stroke (HR: 0.97; 95%CI: 0.58–1.52; P=0.90).

Treatment effect of semaglutide on MACE risk

• Semaglutide reduced the risk of MACE compared with placebo in both participants with a history of CABG (HR: 0.72; 95%CI: 0.54–0.95) and those with no previous CABG (HR: 0.82; 95%CI: 0.73–0.92; P for interaction=0.39).
• During follow-up, the absolute risk reduction with semaglutide versus placebo was greater in patients with a CABG history than those without such a history (2.3% vs. 1.0%).
• Furthermore, semaglutide versus placebo lowered the risks of other CV outcomes such as CV death, all-cause mortality, and coronary revascularization regardless of CABG status (all P for interaction>0.05), except for nonfatal MI (P for interaction=0.041).
• Subgroup analysis of participants with a CABG history demonstrated generally consistent results across subgroups stratified by age, BMI, HbA1c level, or history of MI (all P for interaction>0.05).
• Semaglutide treatment resulted in less weight loss in patients with a CABG history compared with those without (−8.5% vs. −9.5%; P for interaction=0.02).

Conclusion

This prespecified analysis of the SELECT trial among ASCVD patients with overweight or obesity but no diabetes showed participants who had previously undergone CABG had higher risks of MACE and all-cause mortality than those with no history of CABG. Semaglutide consistently reduced the MACE risk compared with placebo in both patients with and with no history of CABG, with a numerically greater absolute risk reduction over the 3-year follow-up in those with a CABG history.

Find this article online at J Am Coll Cardiol.

Watch a video with Subodh Verma, MD, PhD about this analysis recorded at the AHA 2024

References

1. Lv M, Gao F, Liu B, et al. The effects of obesity on mortality following coronary artery bypass graft surgery: a retrospective study from a single center in China. Med Sci Monit. 2021;27:e929912.
2. Carnethon MR, Khan SS. An apparent obesity paradox in cardiac surgery. Circulation. 2017;135:864–866.
3. Ryan DH, Lingvay I, Colhoun HM, et al. Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design. Am Heart J. 2020;229:61–69.
4. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221–2232.