title: Thrombotic complications associated with early and late nonadherence to dual antiplatelet therapy.
abstract: OBJECTIVE
  This study sought to assess the frequency and clinical impact of dual antiplatelet therapy (DAPT) nonadherence.
  
  
  BACKGROUND
  There are limited data on the impact of DAPT nonadherence during the first year after a second-generation drug-eluting stent placement.
  
  
  METHODS
  After successful Endeavor zotarolimus-eluting stent implantation, 2,265 patients were enrolled in a registry with limited exclusions and monitored during 12 months of prescribed DAPT. Predictors of any nonadherence (ANA) at 6 months were analyzed by multivariable analysis, and the association between ANA at 6 or 12 months with the endpoints of death, myocardial infarction, and stent thrombosis was assessed.
  
  
  RESULTS
  The study population included 30% female patients, 34% with diabetes and 36% with acute coronary syndromes. ANA occurred in 208 patients (9.6%) before 6 months and 378 patients (18.5%) before 1 year. Major bleeding (odds ratio [OR]: 12.83, 95% confidence interval [CI]: 7.55 to 21.80, p < 0.001) was the only predictor of ANA at 6 months. In time-dependent analyses, ANA before 6 months was associated with an increased risk of death or myocardial infarction (7.6% vs. 3.0%, p < 0.001) and a numerical increase in stent thrombosis (2.0% vs. 0.9%, p = 0.12). After adjustment for baseline differences, ANA within 6 months remained associated with death or MI (OR: 1.95, 95% CI: 1.02 to 3.75). ANA occurring after 6 months did not increase the risk of subsequent ischemic events.
  
  
  CONCLUSIONS
  DAPT ANA occurs frequently and is associated with increased risk for thrombotic complications if it occurs within the first 6 months. Major bleeding was a significant correlate of DAPT ANA within 6 months. (EDUCATE: The MEDTRONIC Endeavor Drug Eluting Stenting: Understanding Care, Antiplatelet Agents and Thrombotic Events; NCT01069003).
authors.affiliation: Department of Medicine, Cardiology Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address: dcutlip@bidmc.harvard.edu.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Cutlip
authors.affiliation: The Christ Hospital Heart and Vascular Center/The Lindner Research Center, Cincinnati, Ohio.
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.affiliation: Harvard Medical School, Boston, Massachusetts; Department of Medicine, Cardiology Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Laura
authors.initials: L
authors.lastname: Mauri
authors.affiliation: Baylor Heart and Vascular Institute, Baylor University Medical Center, Texas A&M Health Science Center, College of Medicine, Dallas, Texas.
authors.forename: Robert
authors.initials: R
authors.lastname: Stoler
authors.affiliation: Division of Cardiology, University of Vermont College of Medicine, Burlington, Vermont.
authors.forename: Harold L
authors.initials: HL
authors.lastname: Dauerman
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000008:administration & dosage; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000295:instrumentation / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage; D011446:Prospective Studies; D011474:Prosthesis Design; D012042:Registries; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; C489443:zotarolimus; D013988:Ticlopidine; D001241:Aspirin; D020123:Sirolimus
keywords: antiplatelet therapy; stent; thrombosis