Real-world evidence of beneficial effects of cardiac rehabilitation in ACS and CABG patients. Cardiac Rehabilitation Outcome Study Update (CROS-III)

Objective To review the effects of cardiac rehabilitation (CR) in patients with acute coronary syndrome (ACS), coronary artery bypass grafting (CABG) and in mixed populations treated with contemporary interventional, surgical and pharmacological therapy. Methods A systematic review and meta-analysis (PROSPERO CRD42025630588) including randomised controlled trials (RCT) and prospective/retrospective controlled cohort studies (pCCS/rCCS) was performed with total mortality as main endpoint. Additional endpoints were cardiovascular mortality, non-fatal cardiovascular events, and hospital readmissions. Subgroup analysis was performed for age and sex. Results From 40 included studies, 29 studies encompassing 308,514 patients were eligible for this metaanalysis, including 5 newly identified (published between 11/2018-09/2025) studies with 92,571 patients. In pCCS and rCCS, CR-participation was associated with significantly reduced total mortality in patients with ACS (n=41,740; pCCS: HR 0.33, 95%CI 0.15-0.69; rCCS: HR 0.64, 95%CI 0.55-0.75) and with CABG (n=17,998; rCCS: HR 0.65, 95%CI 0.56-0.76). The effects regarding total mortality were similar in sex and age subgroups. Cardiovascular mortality and non-fatal stroke were decreased in ACS and CABG patients. In mixed populations, CR was associated with reduced hospital readmissions for any reason and for any cardiovascular event. Methodological and structural heterogeneity and low patient numbers prevented robust results. Conclusion Based on observational data, participation in CR is associated with an improved prognosis in current patients after ACS, CABG and mixed populations, similarly for sex and age subgroups. Hence, CR should be an integral part of secondary prevention in those patients. Nevertheless, high-quality studies are needed to increase the CR evidence base further.