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Concept: Peripheral vascular disease

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Both vascular function and structure are independent predictors of cardiovascular events. The purpose of this study was to evaluate vascular function and structure of a leg artery in patients with peripheral artery disease (PAD).

Concepts: Cholesterol, Myocardial infarction, Atherosclerosis, Coronary artery disease, Blood vessel, Cardiovascular disease, Peripheral vascular disease, Cardiovascular diseases

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The National Health Service Health Check program in England is the largest cardiovascular risk assessment and management program in the world. We assessed the effect of this program on modelled risk of cardiovascular disease, individual risk factors for cardiovascular disease, prescribing of relevant medications and diagnosis of vascular disease.

Concepts: Medicine, Epidemiology, Risk, Cardiovascular disease, Peripheral vascular disease, Management, Risk management, Risk assessment

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Background Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease. Methods In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months. Results The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49). Conclusions In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).

Concepts: Myocardial infarction, Atherosclerosis, Coronary artery disease, Cardiovascular disease, Stroke, Peripheral vascular disease, Cardiovascular system, Aspirin

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Evidence from large, randomized, controlled peripheral artery disease trials reporting long-term outcomes using drug-coated balloons (DCBs) is limited. Previously, the DCB showed favorable 1-year outcomes compared with conventional percutaneous transluminal angioplasty (PTA), yet durability of the treatment effect with DCBs remains unknown.

Concepts: Atherosclerosis, Coronary artery disease, Cardiology, Peripheral vascular disease, Angioplasty, Balloon

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Although considered a cornerstone therapy, the efficacy and safety of aspirin for prevention of ischemic events in patients with peripheral vascular disease (PVD) remains uncertain. Thus, we aimed to evaluate aspirin use in both symptomatic and asymptomatic patients with PVD.

Concepts: Medicine, Epidemiology, Evidence-based medicine, Systematic review, Randomized controlled trial, Peripheral vascular disease

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Although fruit and vegetable (F&V) consumption is associated with lower risk of coronary heart disease and stroke, its association with peripheral artery disease (PAD) is less certain. We, thus, sought to characterize F&V intake and investigate the association between F&V consumption and presence of PAD in a large community sample.

Concepts: Atherosclerosis, Coronary artery disease, Heart, Peripheral vascular disease, Heart disease, Artery, Coronary circulation, The Association

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Patients with peripheral artery disease (PAD) are at high risk of cardiovascular events and benefit from aggressive secondary prevention; however, changes in the use of cardioprotective medications after incident diagnosis of PAD have not been well described.

Concepts: Medical terms, Coronary artery disease, Blood vessel, Cardiovascular disease, Peripheral vascular disease, Prevention, High school

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The development of tyrosine kinase inhibitors (TKI) has revolutionized management of patients with chronic myeloid leukemia (CML), transforming this fatal disease into a chronic disease with nearly normal life expectancy. Nilotinib is a second generation TKI targeting the oncoprotein BCR-ABL used in patients in the chronic phase of CML. Several research teams have suggested over recent years that nilotinib might be the causal agent in the development or aggravation of vascular disease, particularly in patients with cardiovascular risk factors or an established cardiovascular disease. We report here the case of a patient who developed severe peripheral arterial disease of the lower limbs that worsened despite optimal medical and surgical care, presenting recurrent re-stenoses after different revascularization techniques (bypass, angioplasty…) associated with aggravation of severe trophic disorders to the point of potentially requiring amputation. Discontinuation of nilotinib enabled a stabilization of the arterial lesions and complete healing of the trophic lesions. This case illustrates the importance of recognizing co-morbid conditions in patients with severe vascular disease and to examine the possibility of drug interactions leading to rapid aggravation of arterial disease with no other cause. Studying the pathophysiological impact of TKIs on the vascular system may open new avenues of research for the investigation of factors triggering arteriosclerosis.

Concepts: Medicine, Cancer, Blood, Atherosclerosis, Blood vessel, Cardiovascular disease, Peripheral vascular disease, Chronic myelogenous leukemia

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BACKGROUND : The PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease (PAD) as well as the effect on major adverse limb events. METHODS : FOURIER was a randomized trial of evolocumab versus placebo in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2.2 years. Patients were identified as having PAD at baseline if they had intermittent claudication and an ankle brachial index of <0.85 or if they had a prior peripheral vascular procedure. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina, or coronary revascularization. The key secondary end point was a composite of cardiovascular death, myocardial infarction, or stroke. An additional outcome of interest was major adverse limb events defined as acute limb ischemia, major amputation, or urgent peripheral revascularization for ischemia. RESULTS : Three thousand six hundred forty-two patients (13.2%) had PAD (1505 with no prior myocardial infarction or stroke). Evolocumab significantly reduced the primary end point consistently in patients with PAD (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.66-0.94; P=0.0098 and without PAD (HR 0.86; 95% CI, 0.80-0.93; P=0.0003; Pinteraction=0.40). For the key secondary end point, the HRs were 0.73 (0.59-0.91; P=0.0040) for those with PAD and 0.81 (0.73-0.90; P<0.0001) for those without PAD (Pinteraction=0.41). Because of their higher risk, patients with PAD had larger absolute risk reductions for the primary end point (3.5% with PAD, 1.6% without PAD) and the key secondary end point (3.5% with PAD, 1.4% without PAD). Evolocumab reduced the risk of major adverse limb events in all patients (HR, 0.58; 95% CI, 0.38-0.88; P=0.0093) with consistent effects in those with and without known PAD. There was a consistent relationship between lower achieved low-density lipoprotein cholesterol and lower risk of limb events (P=0.026 for the beta coefficient) that extended down to <10 mg/dL. CONCLUSIONS : Patients with PAD are at high risk of cardiovascular events, and PCSK9 inhibition with evolocumab significantly reduced that risk with large absolute risk reductions. Moreover, lowering of low-density lipoprotein cholesterol with evolocumab reduced the risk of major adverse limb events. CLINICAL TRIAL REGISTRATION : URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.

Concepts: Cholesterol, Myocardial infarction, Atherosclerosis, Coronary artery disease, Cardiovascular disease, Low-density lipoprotein, Atheroma, Peripheral vascular disease

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