Anemia and long-term outcomes after second-generation drug-eluting stent implantation: a retrospective cohort study of mortality and clinical restenosis

Abstract Background Anemia is common in patients undergoing percutaneous coronary intervention (PCI) and is a well-established predictor of bleeding and mortality. However, whether anemia contributes to clinically relevant in-stent restenosis (ISR) in the era of second-generation drug-eluting stents (DES) and competing long-term risks remains uncertain. Methods We retrospectively analyzed 4,117 consecutive adults treated with PCI using second-generation DES at Tehran Heart Center. Anemia was defined as hemoglobin <13 g/dL in men and < 12 g/dL in women. The prespecified primary endpoint was clinically driven target lesion revascularization (TLR) within 5 years, used as a pragmatic proxy for clinical ISR and requiring ischemic symptoms or objective ischemia attributable to the index lesion. Secondary endpoints included all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE). Associations between anemia and outcomes were estimated using Cox proportional hazards models with inverse probability weighting (IPW) based on baseline covariates; Fine–Gray competing-risk models treating death as a competing event were prespecified sensitivity analyses for TLR. Results Anemia was present in 369/4,117 (9.0%) patients. Cumulative TLR occurred in 73 (1.9%) patients, with only 3 events in the anemic group. Given this low event rate, statistical power to detect a difference in TLR was limited. TLR rates did not differ significantly between groups (IPW-adjusted HR 0.27, 95% CI 0.07 to 1.01; p = 0.051), a finding that was consistent in competing-risk analyses. In contrast, mortality was significantly higher in anemic patients (11.5% vs. 4.6%; IPW-adjusted HR 1.87, 95% CI 1.22 to 2.87; p = 0.004). Conclusions In an all-comers cohort undergoing PCI with second-generation DES, baseline anemia was not associated with an increased risk of clinically driven TLR, but it remained a strong independent predictor of long-term mortality. These findings suggest that in contemporary practice, the dominant prognostic impact of anemia is on mortality. However, given the low TLR event rate, the relationship between anemia and clinically manifest restenosis requires further investigation in larger, adequately powered studies.