An updated meta-analysis of clinical outcomes, interventions, and treatment approaches in SMuRF vs. SMuRFless: evidence from 2.6 million ACS patients

Background SMuRFless patients with acute coronary syndrome lack traditional modifiable cardiovascular risk factors, however, concerns remain regarding their potentially poorer clinical outcomes. Methodology This PRISMA-compliant meta-analysis was registered with PROSPERO (CRD420251021614). A single-arm meta-analysis was conducted to estimate the proportion of SMuRFless patients, while a random-effects frequentist meta-analysis compared SMuRFless vs. SMuRF patients. Statistical analyses were performed using R (version 2025.05.0 + 496; Posit). Results Thirty studies comprising 2,650,310 patients were included, of whom 356,716 (13.5%) were SMuRFless. The pooled proportion of SMuRFless patients was 0.11 (95% CI, 0.09–0.14), with substantial heterogeneity ( I 2 = 100.0%, τ 2 = 0.6932). Regarding coronary anatomy, SMuRFless patients had less multivessel disease, LCX involvement, and combined RCA/LCX involvement, but more frequent LAD and LMCA involvement than patients with SMuRFs. Despite a lower burden of comorbidities, SMuRFless status was associated with higher in-hospital mortality (RR, 1.68, 95% CI, 1.41–2.01), 30-day mortality (RR, 2.06, 95% CI, 1.16–3.63), cardiogenic shock (RR, 1.46, 95% CI, 1.24–1.70), and cardiac death (RR, 1.61, 95% CI, 1.03–2.50), whereas 1-year, 2-year, 3-year, and 5-year mortality did not differ significantly between groups. Rates of major bleeding, stroke, recurrent myocardial infarction, PCI, and antiplatelet therapy were comparable; however, SMuRFless patients were less likely to undergo CABG (RR, 0.78, 95% CI, 0.61–0.98) or receive ACE inhibitors/ARBs at discharge (RR, 0.87, 95% CI, 0.79–0.96). Conclusion SMuRFless patients represent a substantial minority of ACS patients and, despite fewer traditional risk factors, are characterized by distinct coronary anatomy and higher observed short-term adverse event rates. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251021614 , identifier CRD420251021614.