Impact of diabetes mellitus on clinical outcomes after percutaneous coronary intervention for chronic total occlusions in the drug-eluting stent era: a systematic review and meta-analysis

Background Diabetes mellitus (DM) is a prevalent comorbidity among patients with chronic total occlusions (CTO) and has been associated with worse outcomes after percutaneous coronary intervention (CTO-PCI). The microvascular dysfunction, endothelial impairment, and pro-inflammatory state characteristic of DM contribute to accelerated atherosclerosis, impaired collateral formation, and enhanced neointimal proliferation. Despite advances in drug-eluting stent (DES) technology, the independent effect of DM on procedural safety and long-term prognosis in this population remains incompletely defined. Methods Following PRISMA standards, five databases were systematically searched up to January 2026 for studies comparing outcomes in diabetic versus non-diabetic patients undergoing CTO-PCI in the DES era. The primary endpoint was MACE. Secondary endpoints included all-cause mortality, cardiovascular mortality, MI, and TVR, evaluated in-hospital, at 1 year, and at long-term follow-up (>1 year). Pooled risk ratios (RR) with 95% CIs were calculated using random-effects models, with heterogeneity assessed by I². Results Eleven studies comprising 9,030 patients (3,470 DM; 5,760 non-DM; mean age 63.8 vs. 62.8 years) were included, with follow-up of up to 60 months. In-hospital outcomes were comparable between groups: MACE (RR 1.08, 95% CI 0.76–1.54), all-cause mortality (RR 1.03, 95% CI 0.42–2.52), and MI (RR 1.16, 95% CI 0.67–2.00), indicating a similar procedural risk. At 1 year, diabetic patients experienced higher rates of MACE (RR 1.31, 95% CI 1.10–1.55) and TVR (RR 1.46, 95% CI 1.23–1.74), while all-cause mortality (RR 1.25, 95% CI 0.89–1.75) and cardiovascular mortality (RR 1.02, 95% CI 0.61–1.72) did not reach statistical significance. At long-term follow-up, diabetic patients demonstrated significantly higher all-cause mortality (RR 1.54, 95% CI 1.03–2.30) and MACE (RR 1.38, 95% CI 1.05–1.81), whereas cardiovascular mortality (RR 0.93, 95% CI 0.38–2.29), MI (RR 1.10, 95% CI 0.77–1.57), and TVR (RR 1.26, 95% CI 0.99–1.60) did not achieve statistical significance. A pooled Kaplan-Meier analysis for MACE, derived from reconstructed individual patient-level data of the included studies, showed a persistently worse event-free survival in diabetic patients throughout follow-up (HR 1.78, 95% CI 1.52–2.09; p<0.001). Heterogeneity was low to moderate (I² 0–57.9%). Conclusion Among patients undergoing CTO-PCI with DES, DM did not increase immediate procedural risk but is associated with significantly worse mid- and long-term outcomes, driven primarily by higher rates of repeat revascularisation and all-cause mortality. Kaplan-Meier curves further confirmed a sustained divergence in event-free survival favoring non-diabetic patients over time. These results identify DM as an important prognostic modifier after CTO-PCI in the contemporary DES era and highlight the need for secondary prevention strategies in this high-risk population.