OBJECTIVES: Our aim was to examine the prognostic importance of hemorrhagic and ischemic complications after percutaneous coronary intervention (PCI) in unselected patients. BACKGROUND: In randomized trials of PCI, major bleeding and periprocedural myocardial infarction (pMI) have been associated with increased mortality. Whether similar associations exist among un-selected PCI patients is unknown. METHODS: We used data from the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) registry-a multicenter registry of unselected patients undergoing PCI-to examine the association between both in-hospital bleeding and pMI and 1-year mortality. Cardiac enzyme levels were assessed in all patients, and pMI was defined as a peak creatine kinase-MB value >/=3x the upper limit of normal. Post-PCI bleeding was classified by Thrombolysis In Myocardial Infarction criteria. RESULTS: After excluding patients with elevated pre-PCI creatine kinase-MB values and ST-segment elevation myocardial infarction at presentation (n = 1,626), a total of 5,961 patients were available for evaluation. Rates of post-PCI bleeding and pMI were 3.0% and 7.1%, respectively; 1-year all-cause mortality was 2.8%. After multivariable adjustment, both post-PCI bleeding (adjusted hazard ratio [HR]: 3.83, 95% confidence interval: 2.48 to 5.90, p < 0.001) and pMI (adjusted HR: 1.84, 95% confidence interval: 1.17 to 2.89, p = 0.009) were independently associated with 1-year mortality. Time period-specific analyses demonstrated that the adjusted HR for bleeding was similar for 30-day mortality and mortality between 1 month and 1 year, while the adjusted HR for pMI was greater for 30-day mortality as compared with mortality between 1 month and 1 year. CONCLUSIONS: Among unselected PCI patients, both post-PCI bleeding and pMI are independently associated with increased 1-year mortality. Continued efforts to reduce these complications after PCI are warranted.

Objective: To evaluate the 5-year clinical outcomes of patients treated with the Endeavor zotarolimus-eluting stent (ZES) in the ENDEAVOR I first-in-human study. Background: ENDEAVOR I was a prospective, nonrandomized, multicenter study of the Endeavor ZES in 100 consecutive patients with symptomatic coronary artery disease (CAD) due to de novo, stenotic lesions in native coronary arteries. Methods: Patients with single or multivessel CAD were eligible to participate, but only one lesion per patient was treated. The lesion had to have >/=50% stenosis, be </=15 mm in length, and located in a vessel with a reference diameter of 3.0-3.5 mm. Major adverse cardiac events (MACE), target lesion revascularization (TLR), target vessel failure (TVF), and stent thrombosis were evaluated 5 years after stent implantation. Results: The cumulative incidence of MACE was 2.0% at 1 year, 3.0% at 2 years, 6.1% at 3 years, 7.2% at 4 years, and 7.2% at 5 years. At 5 years, there were seven patients who had eight events; four noncardiac (cancer) deaths, three cases of TLR, of which one presented as a non-Q-wave MI because of a stent thrombosis at 10 days after the index procedure. There were no late or very late stent thromboses by any definition. TVF at 5 years was 5.2%. Conclusions: Use of the Endeavor ZES to treat symptomatic CAD due to de novo lesions in native coronary arteries resulted in sustained clinical benefits to 5 years, with low rates of MACE, TLR, TVF, and stent thrombosis.(c) 2009 Wiley-Liss, Inc.

OBJECTIVES: The RESOLUTE trial examined the safety and efficacy of a next-generation zotarolimus-eluting coronary stent, Resolute (Medtronic CardioVascular Inc., Santa Rosa, California). BACKGROUND: Revascularization benefits associated with current drug-eluting stents are often diminished in the presence of complex coronary lesions and in certain patient cohorts. Resolute uses a new proprietary polymer coating that extends the duration of drug delivery to match the longer healing duration often experienced in more complex cases. METHODS: The RESOLUTE trial was a prospective, nonrandomized, multicenter study of the Resolute stent in 139 patients with de novo coronary lesions with reference vessel diameters >/=2.5 and </=3.5 mm and lesion length >/=14 and </=27 mm. The primary end point was 9-month in-stent late lumen loss by quantitative coronary angiography. Secondary end points included major adverse cardiac events (MACE) at 30 days, 6, 9, and 12 months; acute device, lesion, and procedure success; and 9-month target vessel failure (TVF), target lesion revascularization (TLR), stent thrombosis, neointimal hyperplastic (NIH) volume, and percent NIH volume obstruction. RESULTS: The 9-month in-stent late lumen loss was 0.22 +/- 0.27 mm. Cumulative MACE were 4.3%, 4.3%, 7.2%, and 8.7% at 30 days, 6, 9, and 12 months, respectively. Acute lesion, procedure, and device success rates were 100.0%, 95.7%, and 99.3%, respectively. At 9 months, TLR was 0.0%, TVF was 6.5%, stent thrombosis was 0.0%, NIH volume was 6.55 +/- 7.83 mm(3), and percent NIH volume obstruction was 3.73 +/- 4.05%. CONCLUSIONS: In this feasibility study, the Resolute stent demonstrated low in-stent late lumen loss, minimal neointimal hyperplastic ingrowth, low TLR, no stent thrombosis, and acceptable TVF and MACE.(The RESOLUTE Clinical Trial; NCT00248079).

BACKGROUND: In the 300-patient SPIRIT II and 1002-patient SPIRIT III randomized trials, the everolimus-eluting stent (EES) compared to the paclitaxel-eluting stent (PES) resulted in reduced angiographic late loss (a primary end point in both trials), noninferior rates of 9-month target vessel failure (a primary end point in SPIRIT III), and reduced rates of target lesion revascularization and major adverse cardiac events (secondary end points). However, neither trial was powered for superiority for clinical end points, and the routine performance of angiographic follow-up may have artificially exaggerated the absolute benefits of EES. The relative efficacy of these 2 stents in patients with diabetes mellitus also remains controversial. We therefore designed a large-scale randomized trial without angiographic follow-up to further assess the differences between these 2 stent platforms. STUDY DESIGN: SPIRIT IV is an ongoing prospective, active-controlled, single-blinded, multicenter clinical trial in which 3690 patients with native coronary artery disease have been randomized 2:1 to EES versus PES. Patients with up to 3 de novo native coronary artery lesions (maximum 2 lesions per epicardial vessel) with length <or=28 mm and reference vessel diameter >or=2.5 to <or=4.25 mm were enrolled at 66 US clinical sites. Clinical follow-up at 30, 180, and 270 days; 1 year; and then yearly for up to 5 years is underway. The primary end point is the rate of ischemia-driven target lesion failure at 1 year, a composite measure of safety and efficacy consisting of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization, with the trial powered for sequential noninferiority and superiority testing. SUMMARY: SPIRIT IV is the largest randomized comparison of 2 DES with completed enrollment. The absence of routine angiographic follow-up will allow an accurate assessment of the absolute differences in the clinical safety and efficacy profile between these devices. The magnitude of the study will also permit significant insights to be gained into the relative performance of the 2 stents in important subgroups, including patients with diabetes mellitus.

Aims: The Endeavor I study was the first clinical study evaluating the safety and feasibility of the Endeavor stent system in the treatment of symptomatic coronary artery disease. The Endeavor Stent System comprises a new cytostatic, antiproliferative and immunosuppressive agent in the same class of drugs as sirolimus,(ABT-578), a phosphorylcholine polymer-based coating, and an established cobalt-alloy stent with thin struts,(Driver stent).Methods and results: One hundred consecutive patients with symptomatic ischemic heart disease due to de novo, obstructive lesions of native coronary arteries were treated with the Endeavor stent system at eight centers in Australia and New Zealand according to contemporary practice. The acute lesion, procedure, and device-deployment success rates were all 100%. Independent core laboratories analyzed quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) data immediately after stent implantation, and at 4 and 12 month follow-up. At 12 months, in-stent late lumen loss was 0.61+/-0.44 mm; in-segment late lumen loss was 0.43+/-0.44 mm, and neointimal hyperplasia volume was 14.2+/-11.8 mm3 (corresponding to a percent volume obstruction of 9.7%+/-8.5%). By QCA and IVUS, the pattern of neointimal hyperplasia was greatest within stent and not at the stent edges. The binary angiographic restenosis rate (defined as >50% diameter stenosis) at 4 and 12 months was 2.1%(2/97) and 5.4%(5/93) respectively. The cumulative incidence of major adverse cardiac events (MACE, defined as death, myocardial infarction, emergent cardiac surgery or repeat revascularization of the index lesion), was 1% at 30 days and 2% at 4 and 12 months. Conclusion: This 100 patient pilot study demonstrates that the Endeavor stent system is a reliable and safe treatment for obstructive coronary disease, providing durable event free clinical outcomes to 12 months by suppression of neointimal proliferation of the target lesion. The results support further pivotal evaluation in larger randomized clinical trials.

The Claudication: Exercise vs Endoluminal Revascularization (CLEVER) Study is a prospective multicenter randomized clinical trial designed to compare the relative clinical and cost-effectiveness of invasive revascularization with stents to supervised exercise rehabilitation in a cohort with moderate to severe claudication due to aortoiliac insufficiency. The study is currently enrolling at twenty-eight sites in the US and Canada. Enrollment of 217 participants is planned, with data collected at baseline, six months, and 18 months. The primary study endpoint is maximum walking duration (MWD) on a graded treadmill test; secondary endpoints include community-based walking, markers of cardiovascular disease risk (body mass index, waist circumference, blood pressure, lipid profile, glucose tolerance, and plasma fibrinogen), health-related quality of life, and cost effectiveness. There are currently sixty randomized participants; recruitment is projected to end in July 2010 and final study results reported in June 2012.

OBJECTIVES: We sought to compare patient-oriented outcomes related to target vessel or nontarget vessel events for sirolimus-eluting stents (SES) versus bare-metal stents. BACKGROUND: SES significantly reduce restenosis but the influence of reduced restenosis on overall patient-oriented outcome has not been reported. METHODS: The study population included 1,057 patients randomized in the SIRIUS (Sirolimus-Eluting Stent in De Novo Native Coronary Lesions) study and followed clinically for 5 years. The primary end point was a composite of all-cause mortality, any myocardial infarction, or any repeat revascularization. In secondary analyses, myocardial infarction and repeat revascularization events attributed to the target vessel or a nontarget vessel were compared by stent type. RESULTS: Patients with an SES were more likely to be free from the primary composite end point at 5 years (60.4% vs. 47.8%, p < 0.001) chiefly due to a sustained reduction in target lesion revascularization for SES (cumulative incidence: 12.5% vs. 28.8%, p < 0.001). There was no difference in the cumulative incidence of myocardial infarction or revascularization attributed to remote segments of the target vessel. Events attributed to the nontarget vessel were frequent and not different for SES versus bare-metal stents (25.7% vs. 25.8%). CONCLUSIONS: The benefit of SES over bare-metal stents for reduced target lesion revascularization is maintained for 5 years. Remote coronary segments of the target vessel and nontarget vessel remain an important cause of future adverse events despite sustained restenosis benefit.

OBJECTIVES: This study sought to evaluate ischemic and bleeding outcomes in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). BACKGROUND: Previous studies have shown that CKD is associated with poor outcomes after PCI. However, these studies were largely conducted before the introduction of DES and aggressive antithrombotic therapy or were performed in the setting of randomized trials. With data from a contemporary registry, we evaluated the influence of CKD on major cardiovascular events and bleeding complications in unselected "real-world" patients undergoing PCI. METHODS: Data from 4,791 patients enrolled in the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) Registry between July 2004 and September 2005 were analyzed. Patients were stratified into 4 groups: creatinine clearance (CrCl)>75, 50 to 75, 30 to 49 and <30 ml/min. RESULTS: During the index hospital stay, there was a step-wise increase in bleeding complications with decreasing CrCl (3.3%, 5.0%, 8.8%, and 14.3%; p < 0.0001 for trend). Lower CrCl was also associated with more frequent death or myocardial infarction (MI) during the initial hospital stay (p = 0.001) and at 1 year (p < 0.001). These findings were confirmed in multivariate analyses that adjusted for baseline differences in demographic, clinical, and angiographic factors. Use of guideline-recommended medications at 1 year, including aspirin, clopidogrel, angiotensin-converting enzyme inhibitors, and statins, also decreased with declining renal function. CONCLUSIONS: Renal function is an independent and powerful predictor of bleeding and ischemic complications in the era of DES and contemporary antithrombotic therapy in patients undergoing PCI. The low use of guideline-recommended drugs among patients with CKD undergoing PCI might contribute to these adverse outcomes and warrants further evaluation.