Management Of Atherothrombosis Research Articles

Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke.

Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals’ bleeding risk. We pooled individual patient data from 6 randomized clinical trials (CAPRIE [Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events], ESPS-2 [European Stroke Prevention Study-2], MATCH [Management of Atherothrombosis With Clopidogrel in High-Risk Patients], CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischemia Trial], and PRoFESS [Prevention Regimen for Effectively Avoiding Second Strokes]) investigating antiplatelet therapy in the subacute or chronic phase after noncardioembolic transient ischemic attack or stroke. Patients were stratified into quintiles according to their predicted risk of major bleeding with the S2TOP-BLEED score. The annual risk of major bleeding and recurrent ischemic events was assessed per quintile for 4 scenarios: (1) aspirin monotherapy, (2) aspirin-clopidogrel versus aspirin or clopidogrel monotherapy, (3) aspirin-dipyridamole versus clopidogrel, and (4) aspirin versus clopidogrel. Net benefit was calculated for the second, third, and fourth scenario. Thirty seven thousand eighty-seven patients were included in the analyses. Both risk of major bleeding and recurrent ischemic events increased over quintiles of predicted bleeding risk, but risk of ischemic events was consistently higher (eg, from 0.7%/y (bottom quintile) to 3.2%/y (top quintile) for major bleeding on aspirin and from 2.5%/y to 10.2%/y for risk of ischemic events on aspirin). Treatment with aspirin-clopidogrel led to more major bleedings (0.9%–1.7% per year), than reduction in ischemic events (ranging from 0.4% to 0.9/1.0% per year) across all quintiles. There was no clear preference for either aspirin-dipyridamole or clopidogrel according to baseline bleeding risk. Among patients with a transient ischemic attack or ischemic stroke included in clinical trials of antiplatelet therapy, the risk of recurrent ischemic events and of major bleeding increase in parallel. Antiplatelet treatment cannot be individualized solely based on bleeding risk assessment.

Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke.

ObjectiveTo study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy.MethodsWe performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of Atherothrombosis With Clopidogrel in High-Risk Patients [MATCH], Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic stroke. We studied incidence rates of bleeding per antiplatelet regimen stratified by time from randomization (≤30, 31–90, 91–180, 181–365, >365 days). We calculated incidence rates per trial and pooled estimates with random-effects meta-analysis. We performed Poisson regression to assess differences between time periods with adjustment for age and sex.ResultsThe incidence of major bleeding on aspirin plus clopidogrel and aspirin plus -dipyridamole was highest in the first 30 days, 5.8 and 4.9 per 100 person-years, respectively, and was significantly higher than at 31 to 90 days (rate ratio 1.98, 95% confidence interval 1.16–3.40 for aspirin plus clopidogrel; rate ratio 1.94, 95% confidence interval 1.24–3.03 for aspirin plus dipyridamole). Incidence rates on aspirin and clopidogrel monotherapy were 2.8 and 2.5 per 100 person-years, respectively, in the first 30 days, with no significant change over time. The time course was similar for gastrointestinal bleeds. There was no early excess of intracranial hemorrhage in patients on either dual or single antiplatelet therapy.ConclusionDual antiplatelet therapy is associated with high early risks of major and gastrointestinal bleeding that decline after the first month in trial cohorts.

Clopidogrel Added to Aspirin Adds No Benefit but Bleeding Risk in Patients With Recent Lacunar Stroke

Patients with transient ischemic attack or ischemic stroke have a high risk of recurrent stroke. Antiplatelet therapy has shown efficacy in secondary stroke prevention and is recommended by guidelines.1–3 In patients without cardiac source of embolism aspirin, clopidogrel or the combination of aspirin and dipyridamole is recommended. In cardiology, the combination of aspirin and clopidogrel was superior to aspirin monotherapy in the prevention of vascular events after acute coronary syndrome4 but carried a higher bleeding risk. In patients with atrial fibrillation the combination of aspirin plus clopidogrel was superior to aspirin alone in preventing strokes,5 but was again associated with a significant higher risk of major bleeds. In early secondary stroke prevention after transient ischemic attack or minor stroke combination, antiplatelet therapy seems to be superior to monotherapy, but larger randomized trials are needed.6,7 Combination antiplatelet therapy carries a consistent higher risk of major bleeding complications than monotherapy. Therefore, the possible benefit of a reduction in vascular events has to be balanced against the bleeding risk, especially in stroke patients. In the Management of Atherothrombosis with Clopidogrel in High-risk patients (MATCH) trial, aspirin plus clopidogrel was investigated against aspirin monotherapy in high-risk patients with recent transient ischemic attack or ischemic stroke.8 Similar to the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, patients with a cardiac source of embolism and significant carotid stenosis requiring surgery were excluded. About 50% of patients were categorized to have small vessel disease with suspected lacunar strokes, but in contrast to the SPS3 trial, …

Education in atherothrombosis

The prevalence of atherothrombosis and the incidence of its various clinical manifestations in Europe and the rest of the world is such that a huge amount of resource is committed to enhancing our understanding of its causes and improving its treatment and prevention. The range and increasing effectiveness of cardiovascular drugs that are available to assist in the prevention and management of atherothrombosis has now provided physicians with an impressive number of options which continues to expand as each year passes. This delivers a challenge to the scientific and clinical communities as to how best to disseminate knowledge in order to direct future research endeavours and maximise the impact of therapeutic advances. We now have a rich variety of media through which such knowledge can be spread, including original research and review articles available in paper and online form, guidelines, updates and position papers of societies such as the European Society of Cardiology, American College of Cardiology and American Heart Association (also available in printed and electronic form), books, conferences (often with presentations available online or through other digital media), websites specialising in cardiovascular research, such as theHeart.org and Cardiosource, and printed materials provided by the pharmaceutical and device industries. The complexity of many of the areas relating to atherothrombosis gives a platform to individuals with expert knowledge who can guide the way to consensus. Yet herein lies a perceived danger that has attracted much attention: the commercial forces behind cardiovascular drug and device development have the potential to influence expert opinion in a way that could bias the presentation of research data for commercial gain (1, 2). Whatever the level of disclosure, the reader of educational materials must identify for themselves the likely bias of an article (3) and be prepared to probe deeper into the literature to form an opinion on the evidence for a particular intervention or else rely on a trusted source. This supplement was supported by an unrestricted educational grant to an academic institution from the pharmaceutical industry. This type of support can take many guises but in this case the companies have had no part in constructing the articles and have not reviewed or approved the content. This is clearly a prerequisite for minimising the risk of bias. Furthermore the articles have been submitted to a formal peer-review process. The aspiration of this process is that high-quality educational materials can be provided to the scientific and clinical communities, accessible freeof-charge via the internet, to inform scientific and clinical debates and research endeavours as well as support therapeutic decision-making in an increasingly complex world of primary and secondary prevention therapies. We hope that readers of this supplement will judge that the authors have succeeded in meeting this aim. Numerous animal models are available for studying the roles of different cell types and extracellular molecules in arterial thrombosis and its sequelae. Mouse models have the advantage of the availability and study feasibility of genetic knock-out lines that can characterise the role of platelet receptor pathways and coagulation proteins in thrombosis to complement and substantiate pharmacological studies. For example, P2Y12 receptor knockout mice have confirmed the role of this receptor in Correspondence to: Prof. Robert F. Storey, MD University of Sheffield Department of Cardiovascular Science Beech Hill Road, Sheffield South Yorkshire, S10 2RX, UK Tel.: +44 114 2713964, Fax: +44 114 2711863 E-mail: r.f.storey@sheffield.ac.uk

Inclusion of Stroke as an Outcome and Risk Equivalent in Risk Scores for Primary and Secondary Prevention of Vascular Disease

Current guideline statements for primary and secondary prevention of cardiovascular disease (CVD) rely on estimates of absolute risk of coronary events. For example, the American Heart Association guidelines on primary prevention state that persons with ≥10% risk over 10 years of myocardial infarction (MI) or coronary death should be considered for antiplatelet therapy with aspirin.1 Similarly, the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines2 state that target low-density lipoprotein level should be based on projected absolute risk of future coronary events rather than on presence or absence of specific risk factors. These guidelines state that patients at high risk of MI and coronary death, defined as an absolute 10-year risk of ≥20%, should have a target low-density lipoprotein level <100 mg/dL and should receive statin therapy if needed to achieve this goal. Stroke, however, is not included as one of the outcomes contributing to these absolute risk levels. Included in the group of patients with elevated risk, moreover, are those who already have ischemic heart disease, as well as patients deemed to be “coronary heart disease (CHD) risk equivalents,” indicating those at the same elevated risk as patients with ischemic heart disease. CHD risk equivalents include patients with diabetes mellitus, those with multiple risk factors that put them at elevated risk based on calculation of their Framingham Score, and patients with “other forms of symptomatic atherosclerotic disease.” The latter group is further defined to include those with peripheral arterial disease (PAD), abdominal aortic aneurysm (AAA), and carotid artery disease. The category of “risk equivalents” in the ATP III guidelines, however, does not include the vast majority (≈80%3) of ischemic stroke patients without carotid artery disease as cause of their stroke. Ischemic stroke is therefore notably excluded from the list of outcomes contributing to …

Drug evaluation of clopidogrel in patients with ischemic stroke

Clopidogrel is an effective antiplatelet medication used for the secondary prevention of ischemic events in patients with various cardiovascular, cerebrovascular and peripheral vascular disease conditions. The objective of this paper is to discuss the role of clopidogrel in ischemic stroke patients and to review the existing data from randomized trials supplemented by pilot and mechanistic studies that supports these indications for its use. An analysis of the mechanism of action and pharmacology of clopidogrel is provided. After Phase III trials, such as the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) and MATCH (Management of Atherothrombosis with Clopidogrel in High-risk patients) trials, the role of clopidogrel in secondary prevention is well defined. The role of clopidogrel in acute ischemic stroke and neurointerventional procedures is evolving based on new pilot trials. At present, there is insufficient data to recommend the use of clopidogrel in acute ischemic stroke. Clopidogrel may be a valuable alternative to aspirin. However, more studies are required to assess the role of clopidogrel in selected patient groups with respect to acute ischemic stroke.

Rate, degree, and predictors of recovery from disability following ischemic stroke

To determine the rate, degree, and predictors of recovery from disabling ischemic stroke. Patients with ischemic stroke enrolled in the Management of Atherothrombosis With Clopidogrel in High-Risk Patients (MATCH) study underwent long-term prospective assessment of their modified Rankin Scale (mRS) score. Disability (functionally dependent state) was defined as mRS > or = 3, and recovery (functionally independent state) was defined as mRS < 3. The timing and the independent predictors of recovery were determined using a Cox proportional hazards multiple regression analysis. Of 7,599 patients enrolled with ischemic stroke or TIA, 1,662 (21.8%) were disabled (mRS > or = 3) at baseline (median of 14 [0 to 96] days after stroke onset). Disability was moderate (mRS 3) in 931 (56%) patients, severe (mRS 4) in 691 (42%), and very severe (mRS 5) in 40 (2%). By 18 months, 877 (52.8%, 95% CI 50% to 55%) patients had recovered, 589 (63%, 60% to 66%) with moderate disability, 281 (41%, 37% to 44%) with severe disability, and 7 (17%, 7 to 33%) with very severe disability. Median time to recovery was 3 months for patients with moderate disability and 18 months for severe disability; 82.5% of severely disabled patients remained so at 18 months. Predictors of recovery were moderate disability (mRS 3) at baseline compared with severe (mRS 4: hazard ratio [HR] 2.13, 1.86 to 2.44) or very severe disabling stroke (HR 5.88, 2.86 to 12.5); younger women (aged <65 years, compared with > or =75 years; HR 1.85, 1.47 to 2.33); decreasing time (days) between the qualifying event and the baseline assessment (HR 1.01, 1.01 to 1.02); and the absence of previous ischemic stroke (HR 1.61, 1.35 to 1.92), concurrent peripheral artery disease (HR 1.61, 1.23 to 2.13), or diabetes (HR 1.30, 1.10 to 1.54). Half of patients with disabling ischemic stroke recovered within 18 months, and recovery was greatest within 6 months. Significant predictors of recovery included the severity of the index stroke and no history of ischemic stroke, peripheral artery disease, or diabetes.

Time frame and predictors of recovery from disability following recurrent ischemic stroke

To assess the rate, degree, and predictors of recovery from a disabled to nondisabled state in patients disabled after recurrent ischemic stroke. Patients with ischemic stroke enrolled in the Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) Study underwent prospective assessment of their modified Rankin score (mRS) at 1, 3, 6, 12, and 18 months after enrollment and after recurrent stroke. Patients disabled (defined as mRS > or = 3) after recurrence were analyzed for recovery (defined as mRS < 3) during the 18 months, and predictors of recovery were sought using a Cox proportional-hazard multiple regression analysis. Three hundred forty-five (54%) of 637 patients were disabled after recurrent ischemic stroke; 115 (33%) patients had been disabled and 230 (66%) nondisabled before stroke recurrence. At recurrence, the degree of disability was moderate (mRS 3) in 135 (39%) patients, severe (mRS 4) in 139 (40%), and very severe (mRS 5) in 71 (21%). After 12 months' median follow-up, 117 (34%, 95% CI: 29 to 39%) had recovered: 68 (50%, 42 to 59%) of 135 moderately disabled, 45 (32%, 25 to 41%) of 139 severely disabled, and 4 (6%, 2 to 14%) of 71 very severely disabled; 70 (20.3%) patients died. From recurrence, median time to recovery was 6 months (mRS 3) and 18 months (mRS 4); 94% with very severe disability had not recovered at 18 months. Independent predictors of recovery were moderate disability at recurrence (mRS 3) compared with severe (mRS 4: hazard ratio [HR] 1.5; 95% CI 1.04 to 2.3) or very severe disability (mRS 5: HR 7.6; 2.7 to 20) and a nondisabled vs disabled state before recurrence (HR 4.0; 2.3 to 6.8). The rate of recovery from recurrent ischemic stroke was greatest in the first 6 months; one-third of patients recovered within 12 months. The significant predictors of recovery were a nondisabled state before recurrence and increasing severity of the recurrent stroke.

Evolving Perspectives on Clopidogrel in the Treatment of Ischemic Stroke

Antiplatelet therapy is indicated for the treatment of ischemic stroke or transient ischemic attack (TIA). Aspirin reduces subsequent occlusive vascular events, including recurrent stroke, by about 25%. In such patients, clopidogrel has been evaluated in an effort to further reduce risk. In the Management of Atherothrombosis with Clopidogrel in High-risk Patients trial, the combination of clopidogrel plus aspirin was compared with clopidogrel alone, and the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance trial tested the addition of clopidogrel to aspirin. Combination therapy with aspirin plus clopidogrel provided no significant incremental benefit compared with aspirin or clopidogrel alone. In addition, combination therapy increased the risk of serious bleeding. On the basis of the current totality of evidence for long-term treatment of survivors of ischemic stroke or TIA, clopidogrel is an effective alternative for patients who are intolerant to aspirin.

Indobufen inhibits tissue factor in human monocytes through a thromboxane-mediated mechanism

To assess whether indobufen, a reversible inhibitor of platelet cyclooxygenase (Cox) activity, affects tissue factor (TF) in human monocytes and to investigate the relationship between Cox-derived products and TF. TF was evaluated in isolated adherent monocytes, both resting and lipopolysaccharide (LPS)-stimulated, in terms of procoagulant activity, protein, and mRNA levels. The expression of TF surface antigen was determined in LPS-stimulated whole blood monocytes by flow cytometry. The levels of the stable thromboxane A2 (TxA2) metabolite, TxB2, and of prostaglandin E2 (PGE2) were measured in monocyte supernatant by immunoenzymatic techniques. Cox-1 and Cox-2 protein level, tyrosine phosphorylation, and mitogen-activated protein kinase (MAP-kinase) activation were determined by Western blot analysis. Indobufen prevents TF expression and activity both in isolated and in whole blood monocytes. Reduction of TxA2 synthesis, coupled with a lack of effect on PGE2 levels and prevention of ERK1/2 phosphorylation are highlighted as the mechanisms through which indobufen negatively affects TF. Data show that indobufen down-regulates TF in monocytes. This novel activity, coupled with the antiplatelet effect of the drug, may add benefit for its use in the management of atherothrombosis.

Clopidogrel: cardiologists’ Panacea Or neurologists’ headache?

Clopidogrel (Plavix) is a potent platelet inhibitor that has been demonstrated to be significantly more effective than aspirin for the prevention of atherothrombotic events in patients with established atherosclerotic disease in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study. Furthermore, the benefit of clopidogrel compared with placebo in patients with acute coronary syndromes, as well as those undergoing percutaneous coronary intervention receiving a standard therapy including aspirin, has been largely demonstrated by the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), Clopidogrel for the Reduction of Events During Observation (CREDO), CLopidogrel as Adjunctive ReperfusIon TherapY-Thrombolysis In Myocardial Infarction (CLARITY-TIMI)28, and Clopidogrel and Metoprolol in Myocardial Infarction Trial/Secon Chinese Cardiac Study (COMMIT/CCS-2) trials. However, in the Management of Atherothrombosis with Clopidogrel in High-risk patients with recent transient ischemic attack or ischemic stroke (MATCH) trial, there was no clinical benefit of adding aspirin versus placebo to a standard therapy of clopidogrel in patients with cerebrovascular disease. The implications of these findings, as well as future perspectives from upcoming trials, shall be discussed herein.

Is clopidogrel the antiplatelet drug of choice for high-risk patients with stroke/TIA?: Yes.

Is clopidogrel the antiplatelet drug of choice for high-risk patients with stroke/TIA?: Yes.

Prevention and Health Services Delivery

The burden of stroke to the health care system in the United States continues to increase. Stroke-related hospital admissions grew from 580 000 in 1988 to 820 000 in 1997, an 18.6% increase after age adjustment.1 More effective stroke prevention provides the primary means of reducing these alarming statistics. This can be accomplished through better implementation of known preventive strategies2 and through research into new approaches to stroke prevention. Diet can affect stroke risk, with epidemiological studies indicating an inverse relationship between fruit and vegetable consumption and cardiovascular events.2 For example, one study including individuals free of cardiovascular disease at baseline found that the relative risk (RR) of stroke was reduced by 31% (RR, 0.69; 95% CI, 0.52 to 0.92) for persons in the highest quintile of fruit and vegetable intake.3 Analysis of data from the National Health and Nutrition Examination Survey (NHANES) Epidemiologic Follow-up Study supports these results.4 The study included 9608 adults aged 25 to 74 years who were free of cardiovascular disease at a baseline evaluation between 1971 and 1975. Consumption of fruits and vegetables ≥3 times per day compared with <1 time per day was associated with a 27% lower stroke incidence (RR, 0.73; 95% CI, 0.57 to 0.95) after adjustment for potential confounders, suggesting the benefit is not attributable to a healthy-user effect. The results reinforce present recommendations for an intake of 5 servings of fruits and vegetables daily. Because fruits and vegetables contain antioxidants, antioxidant food supplements might be expected to have similar benefits. However, a 3-year study of patients with coronary heart disease, low levels of high-density lipoprotein cholesterol, and normal levels of low-density lipoprotein cholesterol found no reduction in cardiovascular end points (death, myocardial infarction, stroke, and revascularization procedures) with the use of antioxidant supplements (800 IU …

Stroke prevention

PREVIEWThe short-term risk of stroke after transient ischemic attack (TIA) is about 10% to 20% in the first 3 months, with much of the risk front-loaded in the first week. Unfortunately, little is known about the best therapies for hyperacute stroke prevention after TIA. A recent trial referred to by the acronym MATCH (for Management of Atherothrombosis With Clopidogrel in High-risk Patients With Recent Transient Ischemic Attack or Ischemic Stroke) provides hypothesis-generating data to suggest that double antiplatelet therapy in the short term may be appropriate. Here, the authors discuss treatment considerations, outlining the current knowledge and stressing the need for formal randomized trials to definitively establish the effectiveness of preventive therapies after minor stroke or TIA.

Long-Term Combination Therapy with Aspirin and Clopidogrel

The possible additive antiplatelet effects of aspirin and clopidogrel have been explored in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) studies. To assess the overall absolute beneficial and/or harmful impact of aspirin and clopidogrel combination therapy compared with monotherapy with either drug, we analyzed the results from both trials in terms of number needed to treat per year. Treating between 35 and 204 at-risk patients for 1 year with combination therapy appeared to prevent 1 patient from experiencing an adverse primary cardiovascular outcome; whereas, about 1 in 63 such patients appeared liable to major bleeding during that period. We determined that the evidence to date indicates no overall advantage for combination therapy with anti-platelet drugs in preference to monotherapy.

“Lacunarization” of Stroke Prevention Studies

HomeStrokeVol. 35, No. 10“Lacunarization” of Stroke Prevention Studies Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUB“Lacunarization” of Stroke Prevention Studies Seemant Chaturvedi Seemant ChaturvediSeemant Chaturvedi Department of Neurology and Stroke Program, Wayne State University, Detroit, Mich Search for more papers by this author Originally published12 Aug 2004https://doi.org/10.1161/01.STR.0000140889.23517.d8Stroke. 2004;35:2238–2239Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 12, 2004: Previous Version 1 To the Editor:Recent stroke prevention studies that have compared differing antithrombotic regimens have been somewhat disappointing in that the more intense antithrombotic regimen has failed to demonstrate superiority over the more conservative regimen. Although this may reflect the fact that established therapy is difficult to improve on,1 I am concerned that the stroke subtype composition in these trials may be distorting the outcome and that they are not reflective of the larger community of patients with ischemic stroke.As examples, in the Warfarin Aspirin Recurrent Stroke Study, the lacunar infarct patients represented 56.1% of the study cohort.2 In the African-American Antiplatelet Stroke Prevention Study, the small vessel infarct subtype accounted for 67.5% of patients.3 Finally, in the recently reported Management of Atherothrombosis With Clopidogrel in High-Risk Patients Study, 52.5% of patients had lacunar infarcts as the qualifying subtype.4Thus, to some extent, each of these studies could be viewed as a referendum on lacunar infarction treatment. In a study that excluded cardioembolic strokes, one would expect that ≈40% of patients would have cryptogenic infarcts, and ≈30% should have large vessel atherosclerotic and lacunar infarcts. The fact that recent studies are enrolling >50% of the study population as lacunar infarction patients does not seem representative of the larger spectrum of ischemic stroke patients. It also impairssubgroup comparison and hypothesis generation for future studies of large vessel atherosclerotic and cryptogenic infarction.Clinical trialists who design future studies of “noncardioembolic stroke” should consider limiting lacunar infarct enrollment to ≤30% of the study cohort and should try to avoid making the entry criteria overly restrictive so that only patients with minimal disability (who tend to be those with lacunar stroke) are allowed in the trial.1 Anderson DC, Goldstein LB. Aspirin: it’s hard to beat. Neurology. 2004; 62: 1036–1037.CrossrefMedlineGoogle Scholar2 Mohr JP, Thompson JL, Lazar RM, Levin B, Sacco RL, Furie KL, Kistler JP, Albers GW, Pettigrew LC, Adams HP Jr, Jackson CM, Pullicino P; Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001; 345: 1444–1451.CrossrefMedlineGoogle Scholar3 Gorelick PB, Richardson D, Kelly M, Ruland S, Hung E, Harris Y, Kittner S, Leurgans S; African-American Antiplatelet Stroke Prevention Study Investigators. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial. J Am Med Assoc. 2003; 289: 2947–2957.CrossrefMedlineGoogle Scholar4 Brass, LM. Management of ATherothrombosis with Clopidogrel in High-risk patients with recent TIA or ischemic stroke. Paper presented at: the European Stroke Conference; May 12–15, 2004; Mannheim-Heidelberg, Germany.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Ioli P (2010) Estudios de no-inferioridad en Neurología: tratamientos nuevos, ¿eficacia demostrada?, Neurología Argentina, 10.1016/S0325-0938(10)70008-8, 2:1, (42-49), Online publication date: 1-Jan-2010. Estol C (2016) About PRoFESS, International Journal of Stroke, 10.1111/j.1747-4949.2005.00010.x, 1:1, (49-50), Online publication date: 1-Feb-2006. October 2004Vol 35, Issue 10 Advertisement Article InformationMetrics https://doi.org/10.1161/01.STR.0000140889.23517.d8PMID: 15308786 Originally publishedAugust 12, 2004 Keywordsanticoagulantsplatelet aggregationPDF download Advertisement

Long-term management of atherothrombosis.

While clinical trials of specific antithrombotic agents can reduce the risk of vascular events in at-risk patients, understanding the results of these studies is key to optimizing benefit and minimizing risk.

Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke (MATCH): Study Design and Baseline Data

Background: The CAPRIE study showed the superiority of clopidogrel over acetylsalicylic acid (ASA) for reducing the combined risk of major atherothrombotic events in patients with recent myocardial infarction (MI), recent ischaemic stroke (IS) or established peripheral arterial disease. The benefit of clopidogrel over ASA is amplified in high-risk patients. Proof of concept for the benefit of clopidogrel in addition to ASA in patients with coronary manifestations of atherothrombosis was provided by the CURE trial. Methods: MATCH is a randomized, double-blind, placebo-controlled trial that compares clopidogrel and ASA versus clopidogrel alone in high-risk patients with recently symptomatic cerebrovascular disease. Eligible patients have experienced a transient ischaemic attack (TIA) or IS within the last 3 months and have evidence of at least 1 additional risk factor within the last 3 years (prior IS, MI, stable or unstable angina pectoris, diabetes or symptomatic peripheral arterial disease). Patients were randomized to receive ASA 75 mg once daily or placebo, with both groups receiving clopidogrel 75 mg once daily as part of standard therapy. The primary end point is the composite of IS, MI, vascular death and rehospitalization for an acute ischaemic event. The duration of treatment and follow-up is 18 months for each patient. Results: Enrolment was completed in April 2002, with 7,599 patients randomized to receive the study medication. The mean age at randomization was 66 years, and the qualifying event was IS in 78.9% of patients and TIA in 21.1%. The baseline features of the study cohort indicate a population that is at a high risk for atherothrombotic recurrence. Conclusion: MATCH is a major ongoing trial that will provide important data on the benefit of clopidogrel and ASA compared with clopidogrel alone for reduction of vascular ischaemic events in patients with recent TIA or IS who are at high risk of atherothrombotic event recurrence.