Balancing Long-Term Risks of Ischemic and Bleeding Complications After Percutaneous Coronary Intervention With Drug-Eluting Stents

Abstract

Although trials comparing antiplatelet strategies after percutaneous coronary intervention report average risks of bleeding and ischemia in a population, there is limited information to guide choices based on individual patient risks, particularly beyond 1 year after treatment. Patient-level data from Patient Related Outcomes With Endeavor vs Cypher Stenting Trial (PROTECT), a broadly inclusive trial enrolling 8,709 subjects treated with drug-eluting stents (sirolimus vs zotarolimus-eluting stent), and PROTECT US, a single-arm study including 1,018 subjects treated with a zotarolimus-eluting stent, were combined. The risk of ischemic events, cardiovascular death/non-periprocedural myocardial infarction (MI)/definite or probable stent thrombosis, and bleeding events, Global Use of Strategies to Open Occluded Arteries moderate or severe bleed, were predicted using logistic regression. At median follow-up of 4.1 years, major bleeding occurred in 260 subjects (2.8%) and ischemic events in 595 (6.3%). Multivariate predictors of bleeding were older age, smoking, diabetes mellitus, congestive heart failure, and chronic kidney disease (all p <0.05). Ischemic events shared all the same predictors with bleeding events and gender, body mass index, previous MI, previous coronary artery bypass graft surgery, ST-segment elevation MI on presentation, stent length, and sirolimus-eluting stent use (all p <0.05). Within individual subjects, bleeding and ischemic risks were strongly correlated; 97% of subjects had a greater risk of ischemic events than bleeding. In conclusion, individual patient risks of ischemia and bleeding are related to many common risk factors, yet the predicted risks of ischemic events are greater than those of major bleeding in the large majority of patients in long-term follow-up.

Figure 1

Monthly rate of the combined primary ischemic (cardiovascular death, non-periprocedural MI or definite/probable ST) and primary bleeding endpoint (GUSTO moderate/severe bleeding event) over specified time periods. Temporal distribution of the ischemic and bleeding endpoints.

Figure 2

Individual predicted probabilities of long-term ischemic and bleeding events. Black line represents identical ischemic and bleeding risk within an individual subject. ρ=0.76; p < 0.001 (A). Distribution of the absolute difference in risk of ischemic and bleeding endpoints. Dotted vertical line represents identical ischemic and bleeding risk within an individual subject. Bars on the right side of the line correspond to subjects with greater ischemic risk than bleeding risk. 3.1% of subjects had ischemic risk exceeding bleeding risk. (B). *Negative risk difference represents a higher bleeding risk than ischemic risk.

Figure 2

Individual predicted probabilities of long-term ischemic and bleeding events. Black line represents identical ischemic and bleeding risk within an individual subject. ρ=0.76; p < 0.001 (A). Distribution of the absolute difference in risk of ischemic and bleeding endpoints. Dotted vertical line represents identical ischemic and bleeding risk within an individual subject. Bars on the right side of the line correspond to subjects with greater ischemic risk than bleeding risk. 3.1% of subjects had ischemic risk exceeding bleeding risk. (B). *Negative risk difference represents a higher bleeding risk than ischemic risk.