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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Beijing Municipal Health Commission (Grant number: 2020-1-4032). Background Whether the underlying risk of high bleeding risk (HBR) influences the relationship of high ischemic risk (HIR) features with adverse events after drug-eluting stent implantation remains unclear. The purpose of this study was to evaluate (1) the prognostic effect of ESC guideline-endorsed HIR features on long-term clinical outcomes and (2) whether the outcomes of HIR versus non-HIR features vary by HBR status. Methods Ten thousand one hundred sixty-seven consecutive patients who underwent percutaneous coronary intervention between January 2013 and December 2013 were prospectively enrolled in Fuwai PCI Registry. Patients who are at HIR were defined as: diffuse multivessel disease in diabetic patients, chronic kidney disease, at least three stents implanted, at least three stents lesions treated, bifurcation with two stents implanted, total stent length &amp;gt; 60 mm, or treatment of chronic total occlusion. The definition of HBR was based on the Academic Research Consortium (ARC) for HBR criteria. The primary ischemic outcome was major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, target vessel revascularization and stent thrombosis. The primary bleeding outcome was clinically relevant bleeding, defined according to Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. Results With a 2.4-year median follow-up, 4430 patients (43.6%) having HIR experienced a significantly higher risk of MACE (hazard ratio [HR] adjust : 1.56, 95% confidence interval [CI]: 1.34–1.82; P &amp;lt; 0.001) and device-oriented composite endpoint (composite of cardiac death, target-vessel MI, and target lesion revascularization) (HRadjust : 1.52 [1.27–1.83]; P &amp;lt; 0.001), compared to those having non-HIR. The risk of clinically relevant bleeding did not differ between groups (HRadjust : 0.85 [0.66–1.08]; P = 0.174). Associations between HIR and adverse events were similar in HBR and non-HBR groups, without evidence of interaction (all P interaction &amp;gt; 0.05); however, adverse event rates were highest among subjects with both HIR and HBR. Conclusions ESC guideline-endorsed HIR was associated with significantly increased risk of MACE without any significant differences in clinically relevant bleeding. The presence of ARC-HBR does not emerge as a modifier of cardiovascular risk for patients at HIR, suggesting more potent and longer antiplatelet therapy may be beneficial for this patient population.

Impact of ESC-endorsed high ischemic risk features and ARC-high bleeding risk criteria on clinical outcomes in all-comer patients undergoing PCI