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We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (≥ 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07–4.10; p = 0.03); 2.49 (1.10–5.67; p = 0.03); 1.71 (1.10–2.67; p = 0.02); and 1.73 (1.31–2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD) is common in patients with severe coronary artery disease (CAD) and is considered a relative contraindication to external enhanced counterpulsation (EECP), but there are no data that define the efficacy and safety of EECP in patients with PAD. The International EECP Patient Registry (IEPR) was used to compare initial posttherapy and 2-year follow-up clinical outcomes and adverse event rates in patients with and without PAD. From January 2002 to October 2004, 2126 patients were enrolled in the IEPR, of whom 493 (23%) had a history of PAD. Immediately following EECP, the reduction in angina (≥ 1 Canadian Cardiovascular Society class) was similar in patients with and without PAD (76.6% vs 79.0%, p = 0.27) as was improvement in the Duke Activity Score Index (DASI) score (+4.7% vs +6.1%, p < 0.001). Both angina reduction and DASI score improvement were sustained at 2 years. PAD patients discontinued EECP more frequently (12.0% vs 8.5%, p < 0.05), but lower extremity ulceration did not occur more frequently in patients with PAD (3.7% vs 2.7%, p = 0.26). Rates of death (17.1% vs 8.6%, p < 0.001) and myocardial infarction (9.5% vs 5.0%, p < 0.001) were, as expected, higher in patients with PAD compared to patients without PAD at 2 years. In conclusion, while PAD patients constitute a high-risk cohort with known higher adverse event rates, EECP led to similar short- and longterm improvements in angina and quality of life for individuals with PAD compared to those without PAD. [ABSTRACT FROM AUTHOR]

AT-1015 is a novel selective 5-HT2A serotonin receptor antagonist that is known to impair platelet aggregation and vasoconstriction. Serotonin has been hypothesized to contribute to claudication symptoms in individuals with peripheral arterial disease (PAD) via microvascular vasoconstrictor and thrombotic effects. AT-1015 was thus evaluated in 439 patients with claudication who were randomized in a double-blind, placebo-controlled trial comparing 10mg, 20mg, and 40mg BID versus placebo for 24 weeks. Treadmill walking performance was assessed by peak walking time (PWT) and pain-free walking time (PFWT). Quality of life (QoL) was measured by the Walking Impairment Questionnaire (WIQ) and the Health Status Survey SF-36. Limb hemodynamics was assessed with the ankle-brachial index (ABI). The 40mg arm was terminated prematurely by recommendation of the Data Safety Monitoring Committee due to an excess number of non-fatal myocardial infarctions. At study conclusion, there were no statistically significant differences in the mean change of PWT, PFWT, ABI and QoL between the 10mg and 20mg BID treatment groups compared with placebo. The proportion of patients who experienced an adverse event (AE) was similar across all treatment groups. Antimuscarinic and gastrointestinal AEs were more common in the AT-1015 treatment groups. Two deaths occurred: one in the placebo group and the other in the AT-1015 20mg group. Although a prolongation of the QTc interval was observed in all groups, this was not clinically significant (QTc > 500ms). Mean supine pulse rates were significantly increased in all AT-1015 treatment groups, consistent with predicted antimuscarinic effects. Population pharmacokinetic analysis fit a one-compartment model with first-order absorption and elimination. These data indicate that selective serotonin receptor blockade does not improve exercise tolerance or quality of life in individuals with claudication. [ABSTRACT FROM AUTHOR]