An updated meta-analysis of clinical outcomes, interventions, and treatment approaches in SMuRF vs. SMuRFless: evidence from 2.6 million ACS patients
9 affiliations
- 1College of Medicine, Alfaisal University
- 2Department of Medicine, Nassau University Medical Center
- 3Department of Cardiology, Sheikh Zayed Medical College
- 4Department of Medicine, Allama Iqbal Medical College
- 5Department of Medicine, Khawaja Muhammad Safdar Medical College
- 6Department of Medicine, Pakistan Institute of Medical Sciences
- 7Department of Cardiology, Ch Pervaiz Elahi Institute of Cardiology
- 8Department of Medicine, University Medical and Dental College
- 9Department of Medicine, The Valley Health System Consortium
Abstract
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.
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BibTeX
@article{qazi2026updated,
title = {{An updated meta-analysis of clinical outcomes, interventions, and treatment approaches in SMuRF vs. SMuRFless: evidence from 2.6 million ACS patients}},
author = {Sadia Qazi and Mohammad Hamza Bin Abdul Malik and Muhammad Arham and Anfal Hamza and Muhammad Awais Bin Abdul Malik and Faseeh Haider and Sufyan Shahid and Mishal Khan and Minahil Iqbal and Aleena Sharif and Tahira Nazir and Ayesha Ihsan and Ali Haq},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1931296},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1931296/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An updated meta-analysis of clinical outcomes, interventions, and treatment approaches in SMuRF vs. SMuRFless: evidence from 2.6 million ACS patients
AU - Sadia Qazi
AU - Mohammad Hamza Bin Abdul Malik
AU - Muhammad Arham
AU - Anfal Hamza
AU - Muhammad Awais Bin Abdul Malik
AU - Faseeh Haider
AU - Sufyan Shahid
AU - Mishal Khan
AU - Minahil Iqbal
AU - Aleena Sharif
AU - Tahira Nazir
AU - Ayesha Ihsan
AU - Ali Haq
PY - 2026
DA - 2026/10/29
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1931296
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1931296/full
AB - 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.
SN - 2297-055X
ER -