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Intensive antithrombotic therapy reduces major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Recent studies have suggested heterogeneity in risk and benefit in those with and without concomitant coronary artery disease (CAD) and peripheral revascularization. We evaluated the risk of MACE and MALE in patients with PAD stratified by history of concomitant CAD and prior peripheral revascularization and whether the efficacy and safety of vorapaxar were similar in these subgroups. The TRA 2°P-TIMI 50 trial randomized 26,449 patients with prior MI, ischemic stroke, or PAD to vorapaxar or placebo. This analysis examined the effect of vorapaxar in a broad population of 6136 patients with PAD. Overall, vorapaxar significantly reduced MACE (HR 0.85, 95% CI 0.73, 0.99; p = 0.034) and MALE (HR 0.70, 95% CI 0.53, 0.92; p = 0.011) in patients with PAD. The absolute risk reduction (ARR) for MACE was greater in patients with PAD and CAD versus those with PAD alone (–2.2% vs 0.1%: number needed to treat (NNT) 45 vs 1000). Conversely, the ARR for MALE was higher in those with prior lower extremity revascularization (2.5% vs 0.2%: NNT 40 vs 500). Vorapaxar increased major bleeding (HR 1.39, 95% CI 1.12, 1.71; p = 0.003). The net clinical outcome in all patients with PAD was reduced with vorapaxar (HR 0.82, 95% CI 0.72, 0.94; p = 0.004), with benefits driven by reductions in MACE for those with CAD and by reductions in MALE for those with prior peripheral revascularization. Among patients with PAD, vorapaxar resulted in a net clinical benefit; however, the drivers of benefit were heterogeneous, with greater reductions in MACE in those with concomitant CAD and greater reductions in MALE in those with prior lower extremity revascularization, and unclear benefit in patients with neither. These clinical characteristics may be useful in identifying the subgroups of patients with PAD most likely to benefit from potent antithrombotic therapies. ClinicalTrials.gov Identifier: NCT00526474

Developed in Collaboration With the American Association of Cardiovascular and Pulmonary Rehabilitation, Inter-Society Consensus for the Management of Peripheral Arterial Disease, Society for Cardiovascular Angiography and Interventions, Society for Clinical Vascular Surgery, Society of Interventional Radiology, Society for Vascular Medicine, Society for Vascular Nursing, Society for Vascular Surgery, and Vascular and Endovascular Surgery Society

The Society for Vascular Medicine was founded in 1989. During the subsequent 25 years, the Society has grown to approximately 500 members and has achieved international recognition while making important contributions to vascular disease education, clinical vascular medicine and biology research, and patient care. In celebration of the Society’s 25th anniversary, its past and current presidents reflect on the Society’s history, challenges, and achievements, and emphasize the vital role of the SVM in the discipline of vascular medicine.

Peripheral artery disease (PAD) is a highly prevalent condition that frequently goes undetected and untreated. Socioeconomic factors associated with unrecognized PAD are not known. The ankle–brachial index (ABI) was calculated in 1656 study participants undergoing non-emergent coronary angiography with PAD defined as an ABI

Abstract Peripheral arterial disease (PAD) is common, but often not diagnosed. A biomarker index would be useful to raise suspicion of PAD, so as to trigger appropriate vascular testing and management. The study comprised 540 individuals: 197 individuals with both coronary artery disease and peripheral arterial disease (CAD + PAD); 81 with CAD only; and 262 with no hemodynamically significant disease (NHSD) of the coronary or peripheral arteries. Multiple linear regression was performed to generate a biomarker panel score that could predict ankle–brachial index (ABI). Logistic regression was used to investigate the relationship between disease status and the panel score as well as other risk factors (e.g. age, diabetes status, smoking status). ROC analysis was performed to test the prediction power of the biomarker panel score. Among the plasma markers tested, beta 2 microglobulin (β2M) and cystatin C had the highest correlation with ABI, and higher than any of the conventional risk factors of age, smoking status, and diabetes status. A biomarker panel score derived from β2M, cystatin C, hsCRP, and glucose had an increased association with PAD status (OR = 12.4, 95% confidence interval (CI) 6.6–23.5 for highest vs lowest quartile), which was still significant after adjusting for known risk factors (OR = 7.3, 95% CI 3.6–14.9 for highest vs lowest quartile). In conclusion, after taking into account the traditional risk factors for PAD, a biomarker panel comprising β2M, cystatin C, hsCRP, and glucose adds useful information to assess the risk of disease.

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 micro-vascular 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 10 mg, 20mg, and 40 mg 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 40 mg 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 10 mg and 20 mg 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 20 mg 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.

Vascular diseases encompass pathological conditions and clinical syndromes involving all the arteries, veins and lymphatic vessels, and include such diverse processes as atherosclerosis, aneurysms, thrombosis, embolism, vasculitis, vasospasm, venous insufŽ ciency and lymphedema. These conditions are common and associated with considerable morbidity and mortality. Discoveries in vascular biology and clinical pharmacology and the technological advancement of percutaneous interventions have brought about a rapid evolution in the Ž eld, and the pace is likely to accelerate. Translation of these scientiŽ c achievements to improved care for patients with disorders of the vasculature requires consistent application of preventive strategies, careful choice of diagnostic methods, appropriate selection of therapeutic options and application of rehabilitative strategies based on training and experience. In the USA, vascular surgeons traditionally delivered care to patients with vascular diseases. The introduction of catheter-based endovascular interventions prompted specially trained radiologists and cardiologists to participate as well. The discipline of vascular medicine evolved early in the twentieth century from a foundation in vascular physiology, hemodynamics and thrombosis. A core of physicians with a background in internal medicine has also brought special expertise to the evaluation and management of patients with vascular diseases. Yet the number of vascular medicine specialists lagged behind other medical specialties because of several factors: the absence of subspecialty board certiŽ cation in vascular medicine; a paucity of training programmes due to a lack of funding; a lack of faculty mentors in vascular medicine training programmes; misconceptions that blood vessels are mere conduits and that vascular disorders affect a single organ system; and the perception that there are few effective therapeutic options for patients with vascular diseases other than revascularization. Formal postgraduate education in vascular medicine began at a few programmes in the 1950s but the American Medical Association did not recognize vascular medicine

Renal artery stenosis (RAS) may cause hypertension, azotemia, episodes of flash pulmonary edema and congestive heart failure. Renal artery angioplasty and stenting was performed in 207 patients from 1991 to 1997. Thirty-nine of these patients (19%) underwent renal artery stenting for the control of recurrent episodes of congestive heart failure and flash pulmonary edema. All patients had angiographic evidence of severe (>70%) bilateral RAS (n = 18) or severe RAS to a solitary functioning kidney (n = 21).Sixteen patients (41%) were male and 23 (59%) were female, mean age 69.9 years (range 50- 85 years). Of the 18 patients with bilateral RAS, 12 (66.6%) underwent bilateral stenting. Mean blood pressure decreased from 174/85 6 32/23 mmHg to 148/72 6 24/14 mmHg (p < 0.001). Mean number of blood pressure medications decreased from 3 6 1 to 2.5 6 1 (p = 0.006). Twenty-eight patients (71.8%) had improvement in blood pressure control. The mean serum creatinine decreased from 3.16 6 1.61 to 2.65 6 1.87 (p = 0.06). Six of 39 patients (15.4%) used angiotensin converting enzyme (ACE) inhibitors prior to stenting whereas 19 of 39 patients (48.7%) used ACE inhibitors poststenting (p = 0.004). Twenty of 39 patients (51.4%) demonstrated improvement in serum creatinine, 10 of 39 patients (25.6%) had stabilization of serum creatinine and nine of 39 patients (23%) demonstrated worsening. The number of hospitalizations due to congestive heart failure in the year preceding renal artery stenting was 2.4 6 1.4 and poststenting was 0.3 6 0.7 (p < 0.001). The New York Heart Association Functional Class decreased from 2.9 6 0.9 prestenting to 1.6 6 0.9 poststenting (p < 0.001). Thirty of 39 patients (77%) had no hospitalizations for congestive heart failure during a mean follow-up period of 21.3 months. Nine patients expired during the course of follow up; eight of the nine patients died within the first year after renal artery stenting.Renal artery stenting decreased the frequency of congestive heart failure, flash pulmonary edema, and the need for hospitalization in most patients. Blood pressure was markedly improved in the majority of patients with improved or stabilized renal function. Evaluation for RAS is important in hypertensive patients who present with recurrent congestive heart failure or flash pulmonary edema.

Address for correspondence: Jeffrey W Olin, Professor of Medicine, Director, Vascular Medicine, Zena and Michael A Wiener Cardiovascular Institute and Marie-Josee and Henry R Kravis Center for Cardiovascular Health, One Gustave L Levy Place, Box 1033, New York, NY 10029, USA. Tel: 1 212 241 9454; Fax: 1 212 241 5107; E-mail: jeffrey.olin@msnyuhealth.org calf veins, many vascular laboratories and radiology departments confine the examination to the femoral popliteal regions.4 A 49-year-old woman underwent a cardiac catheterization and several days later noted right leg swelling and tightness of the thigh while walking. A venous duplex Panel A