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

https://doi.org/10.1016/j.amjcard.2015.05.036Get rights and content

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.

Section snippets

Methods

The study population consisted of 9,727 subjects enrolled in the Patient Related Outcomes With Endeavor vs Cypher Stenting Trial (PROTECT) or in the PROTECT US study.11, 12 The PROTECT trial was a large, broadly inclusive, multicenter randomized controlled trial comparing the long-term safety of 2 different DES, the Endeavor zotarolimus-eluting stent (Medtronic Inc, Santa Rosa, CA), and the Cypher sirolimus-eluting stent (Cordis J&J, Fremont, CA); 8,709 subjects were randomized from May 2007 to

Results

Complete follow-up was available for 9,410 patients (96.7% of 9,727 patients). Baseline/procedural characteristics of patients according to the occurrence of each primary end point are listed in Table 1. Median follow-up duration was 4.1 years (interquartile range 4.0 to 5.0). Use of DAPT was assessed at 1, 6, 12, 24, 36, and 48 months and was 96%, 94%, 87%, 39%, 32%, and 27%, respectively. Median DAPT use was 507.0 days (interquartile range 366.0 to 1,119.0).

The long-term event rate was 6.3%

Discussion

The current analysis performed on the data derived from 2 large prospective cohorts with broad inclusion criteria reflecting contemporary interventional cardiology practice, and with clinical event adjudication, showed that the predicted long-term risk of ischemic events (cardiovascular death/non-periprocedural MI/definite or probable stent thrombosis) was greater than the risk of bleeding events (moderate/severe bleeding) in the large majority of patients. In the small subset of patients that

Disclosures

Relation with industry: Dr. Mattenone; Dr. Yeh: salary (Harvard Clinical Research Institute [HCRI]) and grant (HCRI); Dr. Camenzind: none; Dr. Steg: research support (NYU School of Medicine, Sanofi-Aventis, and Servier), consulting fees (Ablynx, Amarin, Astellas, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo-Lilly, GlaxoSmithKline, Medtronic, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, and The Medicines Company), and stockholding (Aterovax); Dr. Wijns: grant (to

References (27)

  • R. Mehran et al.

    Impact of bleeding on mortality after percutaneous coronary intervention results from a patient-level pooled analysis of the REPLACE-2 (randomized evaluation of PCI linking angiomax to reduced clinical events), ACUITY (acute catheterization and urgent intervention triage strategy), and HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trials

    JACC Cardiovasc Interv

    (2011)
  • E.L. Eisenstein et al.

    Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation

    JAMA

    (2007)
  • L. Mauri et al.

    Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents

    N Engl J Med

    (2014)
  • Cited by (0)

    See page 692 for disclosure information.

    View full text