Is clopidogrel superior to aspirin in secondary prevention of vascular disease?

The cornerstone in clinical evidence of the relative efficacy of thienopyridines (clopidogrel, ticlopidine) versus aspirin in the secondary prevention of vascular disease is the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events trial. This trial showed a modest benefit in the reduction of vascular events by clopidogrel. The results differed according to qualifying disorder: myocardial infarction, -3.7%; ischaemic stroke, +7.3%; and peripheral arterial disease, +23.8% (P = 0.042). Similar results were found for ticlopidine after brain ischaemia. The safety of clopidogrel appears to be similar to that of aspirin and better than that of ticlopidine. However, the recent report of thrombotic thrombocytopenic purpura in association with clopidogrel causes concern

Secondary prevention after cerebral ischaemia of presumed arterial origin: is aspirin still the touchstone?

Patients who have had a transient ischaemic attack or nondisabling ischaemic stroke of presumed arterial origin have an annual risk of death from all vascular causes, non-fatal stroke, or non-fatal myocardial infarction that ranges between 4% and 11% without treatment. In the secondary prevention of these vascular complications the use of aspirin has been the standard treatment for the past two decades. Discussions about the dose of aspirin have dominated the issue for some time, although there is no convincing evidence for any difference in effectiveness in the dose range of 30-1300 mg/day. A far greater problem is the limited degree of protection offered by aspirin: the accumulative evidence from trials with aspirin alone and only for cerebrovascular disease of presumed arterial origin as qualifying event indicates that a dose of aspirin of at least 30 mg/day prevents only 13% of serious vascular complications

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Background For parents at high risk for cardiovascular events, presence of cardiovascular disease or risk factors in their offspring may be an indicator of their genetic load or exposure to (unknown) risk factors and might be related to the development of new or recurrent vascular events. Methods In 4,267 patients with vascular disease, hypertension, diabetes, or hypercholesterolemia enrolled in the SMART cohort, the presence of cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking, or overweight) and cardiovascular disease (coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysm) was assessed in their 10,564 children. The relation between presence of cardiovascular disease or cardiovascular risk factors in their offspring and new or recurrent vascular events was determined by Cox proportional hazard analyses. Results Of the patients, 506 (12%) had offspring with cardiovascular disease, hypertension, hypercholesterolemia, or diabetes. Smoking in offspring was present in 1,972 patients (46%), and overweight in 845 patients (20%). During a median follow-up of 7.0 years (interquartile range 3.7-10.4), the composite outcome of myocardial infarction (MI), stroke, or vascular mortality occurred in 251 patients. Patients with offspring with cardiovascular disease, hypertension, hypercholesterolemia, or diabetes had an increased risk of vascular mortality (hazard ratio [HR] 2.9, 95% CI 1.2-7.1), MI (HR 1.6, 95% CI 1.1-2.5), and the composite outcome (HR 1.5, 95% CI 1.1-2.2). Diabetes in offspring was related to an increased risk of the composite outcome (HR 2.7, 95% CI 1.5-5.0), MI (HR 3.3, 95% CI 1.7-6.6), and vascular mortality (HR 3.4, 95% CI 0.8-14.8). Smoking and overweight in offspring were not related to increased vascular risk in parents. Conclusions Presence of cardiovascular disease, hypertension, hypercholesterolemia, and diabetes in offspring, with diabetes mellitus being the most contributing cardiovascular risk factor, is related to an increased risk of developing new or subsequent vascular events in patients already at high vascular risk

Quality of life after infrainguinal bypass grafting surgery

AbstractPurpose: The purpose of this study was to compare quality of life in patients with and without various ischemic complications after infrainguinal bypass grafting surgery for occlusive vascular disease. Methods: A sample of patients (n = 746) randomized in the Dutch BOA study (n = 2645), a multicenter trial that compared the effectiveness of oral anticoagulant therapy with aspirin in the prevention of infrainguinal bypass graft occlusions, was entered in this study. On the basis of clinical outcomes of the trial, the patients were grouped as follows: patients with patent grafts (n = 409); patients with nontreated graft occlusions, subdivided into an asymptomatic group (n = 32) and a symptomatic group (n = 65); patients with subsequent revascularizations (n = 194); patients with amputations (n = 36); and patients with failed secondary revascularizations followed by secondary amputation (n = 38). In case an outcome event occurred, the patients were regrouped accordingly. Every half year, the patients completed a Short Form–36 and a EuroQol questionnaire. A multilevel model was used for repeated measure analysis. Results:The mean follow-up time was 21 months. The quality of life in patients with nontreated asymptomatic occlusions was roughly similar to the quality of life in patients with patent grafts. Patients with symptomatic nontreated occlusions had the lowest outcome with regard to pain as compared with the other groups. Furthermore, physical and social functioning was lower for these patients than for patients with patent grafts. Revascularizations, successful or not, negatively affected pain, social functioning, and physical and emotional role. After successful revascularization, some improvement was observed in pain, physical and social functioning, and general and mental health as compared with the group with nontreated symptomatic occlusions. Amputation deteriorated physical functioning strikingly, especially after failed secondary revascularization. These patients also had the lowest scores of all the groups in the dimensions of social functioning, physical and emotional role, and mental health. EuroQol score showed deterioration of quality of life after all events, except for asymptomatic occlusions. The same patterns emerged if we stratified our analysis according to the indication for the initial operation: claudication or limb salvage. Quality of life was constant over time in all the groups in the observed period. Conclusion: Quality of life in patients with asymptomatic occluded grafts is similar to quality of life in patients with patent grafts. Revascularization of symptomatic occluded grafts improves quality of life to a certain extent. Amputation, in particular after failed secondary revascularization, seemed to be the lowest possible outcome. The results of the Short Form-36 and EuroQol measurements were in line with the clinical expectations. The association of disease severity with scores on the instruments supports the construct validity of these outcome measures for an objective assessment of quality of life in controlled studies. (J Vasc Surg 1999;29:913-9.

Cost-effectiveness of oral anticoagulants versus aspirin in patients after infrainguinal bypass grafting surgery

AbstractPurpose: Several antithrombotic therapies are available for the treatment of patients with peripheral vascular diseases. It is unknown how quality of life and costs of treatment are influenced by different therapies. This study assessed the cost-effectiveness of oral anticoagulants versus aspirin in patients after infrainguinal bypass grafting surgery. Methods: Clinical outcome events and event-free survival were collected from 2650 patients in 77 centers who participated in the Dutch Bypass Oral anticoagulants or Aspirin trial. Approximately half the patients had critical ischemia; 60% received vein grafts, and 20% had femorocrural bypass grafts. A model that was primarily driven by clinical outcome events was used as a means of determining quality of life (EuroQol EQ-5D) and costs for each patient. The main outcome measure was the incremental health care costs in relation to the additional number of quality-adjusted life years and the additional number of event-free years. Results: The mean costs during the 21 months of follow-up were ϵ 6875 per patient in the oral anticoagulants group versus ϵ 7072 in the aspirin group (difference, 197; 95% CI, –746 to 343). The event-free survival was 1.10 years in the group treated with oral anticoagulants versus 1.09 years in the group treated with aspirin (difference, 0.01; 95% CI, –0.07 to 0.08), whereas the corresponding quality-adjusted life years were 1.06 and 1.05, respectively (difference, 0.01; 95% CI, –0.03 to 0.06). Conclusion: Health care costs, event-free survival, and quality-adjusted life years in patients after infrainguinal bypass surgery were not different in patients treated with aspirin and patients treated with oral anticoagulants. The extra costs of monitoring patients treated with oral anticoagulants were limited and play no role in the decision for treatment. (J Vasc Surg 2001;34:254-62.

Assessment of collateral status by dynamic ct angiography in acute mca stroke: Timing of acquisition and relationship with final infarct volume

BACKGROUND AND PURPOSE: Dynamic CTA is a promising technique for visualization of collateral filling in patients with acute ischemic stroke. Our aim was to describe collateral filling with dynamic CTA and assess the relationship with infarct volume at follow-up. MATERIALS AND METHODS: We selected patients with acute ischemic stroke due to proximal MCA occlusion. Patients underwent NCCT, single-phase CTA, and whole-brain CT perfusion/dynamic CTA within 9 hours after stroke onset. For each patient, a detailed assessment of the extent and velocity of arterial filling was obtained. Poor radiologic outcome was defined as an infarct volume of\70 mL. The association between collateral score and follow-up infarct volume was analyzed with Poisson regression. RESULTS: Sixty-one patients with a mean age of 67 years were included. For all patients combined, the interval that contained the peak of arterial filling in both hemispheres was between 11 and 21 seconds after ICA contrast entry. Poor collateral status as assessed with dynamic CTA was more strongly associated with infarct volume of 70 mL (risk ratio, 1.9; 95% CI, 1.3-2.9) than with single-phase CTA (risk ratio, 1.4; 95% CI, 0.8-2.5). Four subgroups (good-versus-poor and fast-versus-sl

A replication study of genetic risk loci for ischemic stroke in a Dutch population: A case-control study

We aimed to replicate reported associations of 10 SNPs at eight distinct loci with overall ischemic stroke (IS) and its subtypes in an independent cohort of Dutch IS patients. We included 1,375 IS patients enrolled in a prospective multicenter hospital-based cohort in the Netherlands, and 1,533 population-level controls of Dutch descent. We tested these SNPs for association with overall IS and its subtypes (large artery atherosclerosis, small vessel disease and cardioembolic stroke (CE), as classified by TOAST) using an additive multivariable logistic regression model, adjusting for age and sex. We obtained odds ratios (OR) with 95% confidence intervals (95% CI) for the risk allele of each SNP analyzed and exact p-values by permutation. We confirmed the association at 4q25 (PITX2) (OR 1.43; 95% CI, 1.13-1.81, p = 0.029) and 16q22 (ZFHX3) (OR 1.62; 95% CI, 1.26-2.07, p = 0.001) as risk loci for CE. Locus 16q22 was also associated with overall IS (OR 1.24; 95% CI, 1.08-1.42, p = 0.016). Other loci previously associated with IS and/or its subtypes were not confirmed. In conclusion, we validated two loci (4q25, 16q22) associated with CE. In addition, our study may suggest that the association of locus 16q22 may not be limited to CE, but also includes overall IS

Distribution of Cardioembolic Stroke:A Cohort Study

Background: A cardiac origin in ischemic stroke is more frequent than previously assumed, but it is not clear which patients benefit from cardiac work-up if obvious cardiac pathology is absent. We hypothesized that thromboembolic stroke with a cardiac source occurs more frequently in the posterior circulation compared with thromboembolic stroke of another etiology. Methods: We performed a multicenter observational study in 3,311 consecutive patients with ischemic stroke who were enrolled in an ongoing prospective stroke registry of 8 University hospitals between September 2009 and November 2014 in The Netherlands. In this initiative, the so-called Parelsnoer Institute-Cerebrovascular Accident Study Group, clinical data, imaging, and biomaterials of patients with stroke are prospectively and uniformly collected. We compared the proportions of posterior stroke location in patients with a cardiac stroke source with those with another stroke etiology and calculated risk ratios (RR) with corresponding 95% CI with Poisson regression analyses. To assess which patient or disease characteristics were most strongly associated with a cardiac etiology in patients with ischemic stroke, we performed a stepwise backward regression analysis. Results: For the primary aim, 1,428 patients were eligible for analyses. The proportion of patients with a posterior stroke location among patients with a cardiac origin of their stroke (28%) did not differ statistically significant to those with another origin (25%), age and sex adjusted RR 1.16; 95% CI 0.96-1.41. For the secondary aim, 1,955 patients were eligible for analyses. No recent history of smoking, no hyperlipidemia, coronary artery disease, a higher age, and a higher National Institutes of Health Stroke Scale (NIHSS) score were associated with a cardiac etiology of ischemic stroke. Conclusions: We could not confirm our hypothesis that thromboembolic stroke localized in the posterior circulation is associated with a cardioembolic source of ischemic stroke, and therefore posterior stroke localization on itself does not necessitate additional cardiac examination. The lack of determinants of atherosclerosis, for example, no recent history of smoking and no hyperlipidemia, coronary artery disease, a higher age, and a higher NIHSS score are stronger risk factors for a cardiac source of ischemic stroke