Faculty Bibliography

OBJECTIVES: This study sought to report the final 5-year outcomes of the ENDEAVOR IV (A Randomized, Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions) trial comparing the Endeavor zotarolimus-eluting stent (E-ZES) (Medtronic, Santa Rosa, California) with the Taxus paclitaxel-eluting stent (PES) (Boston Scientific, Natick, Massachusetts) in patients with single de novo coronary lesions. BACKGROUND: Primary results of the ENDEAVOR IV trial demonstrated similar clinical outcomes with E-ZES and PES. Concerns with regard to late adverse clinical events with drug-eluting stents highlight the need for long-term follow-up with these devices. METHODS: Late outcomes after the use of E-ZES and PES were examined in the multicenter randomized ENDEAVOR IV trial in cumulative and landmark analyses. Assessed outcomes were related to device efficacy and patient safety. RESULTS: At 5 years, clinical data were available for 722 (93.4%) E-ZES patients and 718 (92.6%) PES patients. Overall rates of target lesion revascularization (7.7% vs. 8.6%, p = 0.70) and target vessel failure were similar (17.2% vs. 21.1%, p = 0.061) with E-ZES compared with PES. The incidence of cardiac death or myocardial infarction (MI) was lower with E-ZES (6.4% vs. 9.1%, p = 0.048), primarily driven by a lower rate of target vessel MI with E-ZES (2.6% vs. 6.0%, p = 0.002). Although overall definite/probable stent thrombosis rates were similar between stents (1.3% vs. 2%, p = 0.42), rates of very late stent thrombosis (0.4% vs. 1.8%, p = 0.012) and late MI events (1.3% vs. 3.5%, p = 0.008) were significantly lower with E-ZES compared with PES. CONCLUSIONS: These data demonstrate the durable efficacy and safety of E-ZES compared with PES for the treatment of de novo coronary lesions. Significant improvements in late safety outcomes were observed with E-ZES but should be considered hypothesis-generating, given the limited statistical power of the trial. (The ENDEAVOR IV Clinical Trial: A Trial of a Coronary Stent System in Coronary Artery Lesions; NCT00217269).

BACKGROUND: Patients with non-ST-segment elevation acute coronary syndrome (ACS) are managed with either a routine invasive strategy, in which all patients receive coronary angiography, or a selective invasive strategy, in which only patients with refractory or inducible ischemia receive coronary angiography. PURPOSE: To evaluate whether a routine invasive strategy improves cardiovascular outcomes more than a selective invasive strategy in patients with non-ST-segment elevation ACS. DATA SOURCES: English-language publications in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from 1966 to 18 September 2007. STUDY SELECTION: Two investigators independently reviewed searches and selected trials that compared death or myocardial infarction outcomes among adults with non-ST-segment elevation ACS by randomly assigning patients to either a routine invasive strategy or a selective invasive strategy. DATA EXTRACTION: Three investigators independently abstracted data from trial reports by using standardized forms. DATA SYNTHESIS: 10 trials with a total of 10,648 patients (mean age, 62 years; 71% male; median follow-up, 16.5 months) were found. Trial participants had typical symptoms of unstable angina and frequently had a positive electrocardiogram or marker evidence of myocardial ischemia. Of the 5330 participants assigned to the routine invasive strategy group, 847 had the composite outcome of death or nonfatal myocardial infarction, compared with 928 of 5318 participants assigned to the selective invasive strategy group (relative risk, 0.90 [95% CI, 0.74 to 1.08]). Four hundred thirty-eight patients in the routine invasive strategy group and 463 in the selective invasive strategy group died (relative risk, 0.95 [CI, 0.80 to 1.14]). Four hundred ninety and 569 nonfatal myocardial infarctions, respectively, occurred in the 2 groups (relative risk, 0.86 [CI, 0.68 to 1.08]). LIMITATIONS: Methodology, protocols, and outcome definitions differed substantially among the trials. The lower bound of the CI for the pooled results did not rule out the superiority of the routine invasive strategy. CONCLUSION: Available trial evidence is heterogeneous and insufficient for comparing routine and selective invasive strategies. Therefore, in patients with non-ST-segment elevation ACS a routine invasive strategy cannot be proven to reduce deaths or nonfatal myocardial infarction.