title: Usefulness of postmarket studies to evaluate long-term safety of coronary eluting stents (from the ENDEAVOR and PROTECT Programs).
abstract: Differences in enrollment criteria and protocol requirements are believed to affect patient representation and outcomes from premarket and postmarket surveillance (PMS) trials. These differences have not been assessed in studies evaluating coronary stenting. We aimed to assess differences in clinical profile and long-term outcomes in patients enrolled into premarket versus PMS trials assessing the Endeavor zotarolimus-eluting stent (E-ZES). We pooled patient-level data for 2,132 and 4,357 E-ZES-treated subjects enrolled into the ENDEAVOR program (premarket) and Patient Related OuTcomes with Endeavor versus Cypher stenting Trial (PMS), respectively. Follow-up data were available through 3 years. Baseline characteristics and outcomes of patients enrolled in the 2 groups were compared. Propensity score-adjusted Cox proportional hazards models were used to assess the effect of differences in baseline characteristics. We also adjusted for protocol-mandated repeat angiography to account for differences in follow-up requirements. Despite significant differences in baseline characteristics, the unadjusted 3-year rates of major adverse cardiac events, major adverse cardiac and cerebrovascular events, and target vessel failure were similar (premarket vs PMS: 11.9% vs 12.7%, p = 0.369; 12.7% vs 13.9%, p = 0.191; and 13.8% vs 13.4%, p = 0.667, respectively). However, PMS trials had significantly higher rates of myocardial infarctions (p = 0.005) and definite or probable stent thrombosis (p = 0.016). After propensity score adjustment, myocardial infarction rates remained significantly different (hazard ratio 0.53, 95% confidence interval 0.30 to 0.91). To conclude, premarket and PMS trials assessing E-ZES implantation enrolled different patients. PMS trials were shown to be essential for the detection of safety signals.
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts; Department of Biostatistics, Boston University, Boston, Massachusetts. Electronic address: moshe.vardi@hcri.harvard.edu.
authors.forename: Moshe
authors.initials: M
authors.lastname: Vardi
authors.affiliation: Department of Biostatistics, Boston University, Boston, Massachusetts.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Perez
authors.affiliation: Department of Biostatistics, Boston University, Boston, Massachusetts.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Griffin
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: David A
authors.initials: DA
authors.lastname: Burke
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts; Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Yeh
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Cutlip
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000453:epidemiology / Q000517:prevention & control*; D054855:Drug-Eluting Stents / Q000592:standards*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000601:surgery*; D011358:Product Surveillance, Postmarketing; D016016:Proportional Hazards Models; D011474:Prosthesis Design; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult