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Peripheral arterial disease increases cardiovascular risk in many patient populations. The risks associated with an abnormal ankle-brachial index (ABI) in patients with type 2 diabetes and stable coronary artery disease have not been well described with respect to thresholds and types of cardiovascular events.We examined 2,368 patients in the BARI 2D trial who underwent ABI assessment at baseline. Death and major cardiovascular events (death, myocardial infarction and stroke) during follow-up (average 4.3 years) were assessed across the ABI spectrum and by categorized ABI: low (≤0.90), normal (0.91-1.3), high (1.3), or noncompressible.A total of 12,568 person-years were available for mortality analysis. During follow-up, 316 patients died, and 549 had major cardiovascular events. After adjustment for potential confounders, with normal ABI as the referent group, a low ABI conferred an increased risk of death (relative risk [RR] 1.6, CI 1.2-2.2, P = .0005) and major cardiovascular events (RR 1.4, CI 1.1-1.7, P = .004). Patients with a high ABI had similar outcomes as patients with a normal ABI, but risk again increased in patients with a noncompressible ABI with a risk of death (RR 1.9, CI 1.3-2.8, P = .001) and major cardiovascular event (RR 1.5, CI 1.1-2.1, P = .01).In patients with coronary artery disease and type 2 diabetes, ABI screening and identification of ABI abnormalities including a low ABI (1.0) or noncompressible artery provide incremental prognostic information.

Abstract 2309 Introduction: We have previously investigated the incidence of acute coronary syndrome (ACS) events in patients treated with the new oral, reversible, direct thrombin inhibitor, dabigatran etexilate (DE) compared with enoxaparin in the treatment and post-treatment periods in patients undergoing major orthopaedic surgery in three phase III trials (RE-MODEL™, RE-NOVATE® and RE-MOBILIZE®). Whether identified through local investigator reporting or blinded central event adjudication, no significant differences in ACS event rates were detected among orthopaedic surgery patients treated with DE compared with enoxaparin during or after treatment. Overall event rates were low, consistent between investigator and centrally adjudicated assessments, and without evidence for a ‘rebound’ effect for either agent in this post-surgical population. In a pooling with a fourth trial (RE-NOVATE® II), we have now conducted an analysis of investigator-reported adverse events possibly related to ACS from 10,148 treated patients. Methods: Patients in the RE-MODEL™, RE-NOVATE®, RE-NOVATE® II and RE-MOBILIZE® trials were randomized to receive oral DE 150 mg (n = 2737) or 220 mg (n = 3692) once daily, or subcutaneous enoxaparin (n = 3719) for 6–35 days, and were followed for 90 days post-surgery. Potential ACS events during treatment were identified based on investigator-reported adverse events classified using pre-specified Standard Medical Dictionary for Regulatory Authorities (MedDRA) Queries (SMQs). This list included terms relating to locally diagnosed ACS as well as broader MedDRA terms that could reflect undiagnosed ACS. Results: In all four trials, adverse events included in the SMQ ‘ischaemic heart disease’ (sub-terms myocardial infarction [MI], acute MI, angina pectoris, myocardial ischaemia, ACS, unstable angina, coronary artery disease, coronary artery occlusion, cardiac enzymes increased, electrocardiogram ST segment depression, electrocardiogram T wave abnormal, ischaemic cardiomyopathy and troponin increased) were reported by the investigator in 16 (0.4%) and 32 (1.2%) patients in the DE 220 mg and DE 150 mg groups, respectively, compared to 25 (0.7%) in the enoxaparin group during treatment. The incidence of individual adverse event terms possibly related to ACS in the respective treatment groups (DE 220 mg, DE 150 mg and enoxaparin) was as follows: MI 3 (0.1%), 11 (0.4%) and 9 (0.2%); acute MI 1 (0.0%), 3 (0.1%) and 1 (0.0%); ACS 1 (0.0%), 0 (0.0%) and 0 (0.0%); unstable angina 1 (0.0%), 0 (0.0%) and 0 (0.0%). Conclusions: The analysis of > 10,000 patients showed no significant differences in investigator-reported ACS-related adverse event rates among orthopaedic surgery patients during treatment, comparing DE with enoxaparin. This is in agreement with, and supports previous findings of, investigator-related and centrally adjudicated ACS events from three trials. Disclosures: Eriksson: Bristol-Myers Squibb: Consultancy; Bayer: Consultancy; Astellas: Consultancy. Smith:Boehringer Ingelheim: Employment. Caprini:ESAI: Consultancy; Pfizer: Consultancy; GSK: Consultancy; Sanofi: Consultancy; Boehringer Ingelheim: Consultancy; Covidien: Consultancy. Hantel:Boehringer Ingelheim: Employment. Clemens:Boehringer Ingelheim: Employment. Feuring:Boehringer Ingelheim: Employment.

Background Clopidogrel is widely used in diabetic patients after vascular events; however, the ability of this thienopyridine to yield additional antiplatelet protection on top of aspirin has never been explored in a controlled study with comprehensive assessment of platelet activity. The objective of this study was to compare the antiplatelet profiles of clopidogrel + aspirin in combination (C + ASA) versus aspirin alone (ASA) in patients with type 2 diabetes mellitus. Methods Seventy patients with documented diabetes already treated with antecedent aspirin were randomly assigned to receive C + ASA or ASA in the PLUTO-Diabetes trial. Platelet studies included adenosine diphosphate-, collagen-, and arachidonic acid-induced aggregometry; PFA-100 (Dade-Behring, Miami, FL) and Ultegra (Accumetrics, San Diego, CA) analyzers; and expression of 6 major receptors by flow cytometry at baseline and at day 30 after randomization. Results There were no differences in the baseline clinical and platelet characteristics between the C + ASA and ASA groups, or subsequent significant changes in platelet biomarkers in the ASA group, except for diminished collagen-induced aggregation ( P = .02). In contrast, when compared with the ASA group, therapy with C + ASA resulted in significant inhibition of platelet activity assessed by adenosine diphosphate aggregation ( P = .0001); closure time prolongation ( P = .0003) and reduction of platelet activation units with Ultegra ( P = .0001); and expression of platelet/endothelial cell adhesion molecule 1 ( P = .002), glycoprotein IIb/IIIa antigen ( P = .0002), and activity ( P = .0001). Conclusion Treatment with C + ASA for 1 month provides significantly greater inhibition of platelet activity than ASA alone in diabetic patients in this small randomized trial. However, despite dual antiplatelet regimen, diabetic patients exhibit high residual activity of some platelet biomarkers, including unaffected protease-activated receptor 1 receptor expression.

Background Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for refractory angina which is mainly used for patients (pts) who are not candidates for further invasive revascularization. This report examines whether pts who have the option of further invasive revascularization (CR) demonstrate a comparable initial and sustained 2-year response to EECP as those who are not candidates for revascularization (NCR). Methods Consecutive angina pts enrolled in the International EECP Patient Registry were grouped by potential for further revascularization. Baseline demographics were recorded and outcomes were tracked for 2 years post EECP. Statistical analysis was by chi-square test, t test and Kaplan-Meier survival methods. Significance was defined as p Results There were 1,335 NCR pts and 204 CR pts. CR were significantly younger (64.3 ± 11.3 vs. 66.7 ± 10.7 years), with more recently diagnosed CAD (10.8 ± 9.1 vs. 11.6 ± 8.2 years) and had less severe angina (CCS class III/IV 83.3% vs. 91.8%). They were less likely to have prior CABG (55.2% vs 74%), CHF (16.9% vs 35.1%), LVEF Conclusions EECP effectively provided comparable sustained relief from angina in CAD pts regardless of their candidacy for further revascularization. However NCR patients presented with a more severe clinical profile at baseline, which was reflected in increased mortality and episodes of CHF in follow-up.

OBJECTIVES The study compared the safety and efficacy of ticlopidine with clopidogrel in patients receiving coronary stents. BACKGROUND Stent thrombosis is reduced when ticlopidine is administered with aspirin. Clopidogrel is similar to ticlopidine in chemical structure and function but has fewer side effects; few data are available about its use in stent patients. METHODS We compared 30-day event rates in 500 consecutive coronary stent patients treated with aspirin and clopidogrel (300 mg loading dose immediately prior to stent placement, and 75 mg/day for 14 days) to 827 consecutive stent patients treated with aspirin and ticlopidine (500 mg loading dose and 250 mg twice daily for 14 days). RESULTS Patients treated with clopidogrel had more adverse clinical characteristics including older age, more severe angina, and more frequent infarction within the prior 24 h. Nonetheless, mortality was 0.4% in clopidogrel patients versus 1.1% in ticlopidine patients; nonfatal myocardial infarction occurred in 0% versus 0.5%, stent thrombosis in 0.2% versus 0.7%, bypass surgery or repeat angioplasty in 0.4% versus 0.5%, and any event occurred in 0.8% versus 1.6% of patients, respectively (p = NS). Based on the observed 30-day event rate of 1.6% with ticlopidine, the statistical power of the study was 43% to detect an even rate of 0.5% with clopidogrel, and 75% to detect an event rate with of 4% with clopidogrel, with a p value of 0.05. CONCLUSIONS These data indicate that clopidogrel can be safely substituted for ticlopidine in patients receiving coronary stents.