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A Study of Clopidogrel for the Prevention of TIA and Minor Ischemic Stroke

Overview

About this study

The purpose of this study is to assess the effectiveness of Clopidogrel for preventing the occurance of transient ischemic attacks (TIA) and minor strokes.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

  • Neurological deficit (based on history or exam) attributed to focal brain ischemia and either
    • High risk TIA
      • Complete resolution of the deficit at the time of randomization 
      • ABCD2 score of ≥ 4
    • Minor ischemic stroke
      • Residual deficit with NIHSS of ≤ 3 at the time of randomization
  • Ability to randomize within 12 hours of time last known free of new ischemic symptoms
  • Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy
  • Ability to tolerate aspirin at a dose of 50-325 mg/day

Exclusion Criteria

  • Age < 18 years
  • TIA symptoms limited to isolated numbness, isolated visual changes, or isolated dizziness/vertigo
  • In the judgment of the treating physician, a candidate for thrombolysis, endarterectomy or endovascular intervention, unless the subject declines both endarterectomy and endovascular intervention at the time of evaluation for eligibility
  • Receipt of any intravenous or intra-arterial thrombolysis within 1 week prior to index event
  • Gastrointestinal bleed or major surgery within 3 months prior to index event
  • History of nontraumatic intracranial hemorrhage
  • Clear indication for anticoagulation (e.g., warfarin, heparin) anticipated during the study period (atrial fibrillation, mechanical heart valve, deep venous thrombosis, pulmonary embolism, antiphospholipid antibody syndrome, hypercoagulable state)
  • Qualifying ischemic event induced by angiography or surgery
  • Severe non-cardiovascular comorbidity with life expectancy < 3 months
  • Contraindication to clopidogrel or aspirin
    • Known allergy
    • Severe renal (serum creatinine >2 mg/dL or 176.8umol/L) or hepatic insufficiency
      • Prior or concurrent diagnosis, with International Normalized Ratio (INR) > 1.5
      • Any resultant complication, such as variceal bleeding, encephalopathy, or icterus
    • Hemostatic disorder or systemic bleeding in the past 3 months
    • Current thrombocytopenia (platelet count <100 x10^9/l) or neutropenia (<1 x10^9/l)
    • History of drug-induced hematologic or hepatic abnormalities
  • Anticipated requirement for long-term >7 day non-study antiplatelet drugs (eg, dipyridamole, clopidogrel, ticlopidine), or Non-steroidal Anti-inflammatory Drugs (NSAIDs) affecting platelet function such as prior vascular stent or arthritis
  • Inability to swallow medications
  • At risk for pregnancy
    • Pre or post menopausal woman within 12 months of last menses without a negative pregnancy test 
    • Not committing to adequate birth control (e.g., oral contraceptive, two methods of barrier birth control, or abstinence)
  • Unavailability for follow-up
  • Signed and dated informed consent not obtained from patient
  • Other neurological conditions that would complicate assessment of outcomes during follow-up
  • Ongoing treatment in another study of an investigational therapy or treatment in such a study within the last 7 days
  • Previously enrolled in the POINT study

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Maria Aguilar, M.D.

Closed for enrollment

More information

Publications

  • Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone. Read More on PubMed
  • Statin interference has been suggested among the mechanisms of reduction of the antiplatelet effect of clopidogrel. We thus sought to assess the influence of rosuvastatin on clopidogrel antiplatelet action in high-risk (HR) cardiovascular patients. To set the level of platelet inhibition by combined antithrombotic treatments we retrospectively studied two populations of HR patients, one under aspirin alone, the other under aspirin plus rosuvastatin, before and after addition of clopidogrel. The effects of rosuvastatin compared with atorvastatin were then prospectively investigated in patients who underwent percutaneous coronary intervention (PCI), under clopidogrel and aspirin treatment. Light transmission platelet aggregation (LTA) was studied in response to adenosine diphosphate (ADP) (5 microM) or arachidonic acid (0.5 mM). The inhibitory effect of clopidogrel in reducing ADP-induced LTA was similar in the two HR groups of patients. No difference in ADP-induced platelet aggregation was observed in the two PCI groups of patients with either atorvastatin or rosuvastatin. In conclusion, rosuvastatin does not interfere with the antiplatelet effect of clopidogrel in patients with cardiovascular disease. Read More on PubMed
  • Evidence is available on the effectiveness and costs of treatments to reduce stroke risk in long-term secondary prevention. However, there are few data on the costs and outcomes of urgent assessment and treatment after the onset of transient ischaemic attack (TIA) or minor stroke. The Early use of eXisting PREventive Strategies for Stroke (EXPRESS) study showed that urgent assessment and treatment reduced the 90-day risk of recurrent stroke by about 80%. We now report the effect of the EXPRESS intervention on admissions to hospital, costs, and disability. Read More on PubMed
  • Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. Read More on PubMed
  • Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. Read More on PubMed
  • There are growing data suggesting a clinical relevance of residual platelet aggregation (RPA) in patients undergoing PCI. Drug-drug interaction of statins and clopidogrel has been controversially discussed in ex vivo studies and clinical trials. The aim of the present study was to investigate the effects of peri-procedural statin medication on the metabolization of aspirin and clopidogrel with regard to platelet aggregation and clinical outcome in patients undergoing coronary intervention. Read More on PubMed
  • As many as 300,000 transient ischemic attacks (TIAs) occur in the United States each year, accounting for 0.3% of all Emergency Department visits. An under-recognized and under-treated problem, TIA is associated with up to a 10% risk of subsequent stroke within 7 days and a 25% risk of death at 1 year. Antiplatelet therapy can result in significant reductions in secondary stroke risk. However, nearly 50% of patients with TIA leave the Emergency Department without any medication. This article discusses recent results from major antiplatelet clinical trials in stroke prevention and highlights the need for appropriate and timely initiation of antiplatelet treatment in patients with TIA. Read More on PubMed
  • Clopidogrel is inactive in vitro and is metabolized by hepatic cytochrome P-450-3A4 to produce active metabolites. Unlike pravastatin, atorvastatin is a statin that is subject to metabolism by cytochrome P-450-3A4, and drug-drug interactions with other potent inhibitors of this cytochrome system have been demonstrated. However, the clinical impact of this interaction has created debate. Read More on PubMed
  • It is now clear that transient ischemic attacks and strokes are different manifestations of the same disease and transient ischemic attacks are often warning signs of an impending stroke. Unfortunately, it is unclear when the next event will occur in an individual patient. It is critical for emergency physicians to know what the true risk of stroke is for patients who present to the emergency department (ED) with a transient ischemic attack and a normal neurologic examination result. We perform an evidence-based emergency medicine shortcut review of the short-term outcome of stroke among patients diagnosed in the ED with a transient ischemic attack. Read More on PubMed
  • Risk of a subsequent stroke following an acute transient ischemic attack (TIA) or minor stroke is high. The ABCD(2) tool was proposed as a method to triage these patients using five clinical factors. Modern imaging of the brain was not included. The present study quantified the added value of magnetic resonance imaging (MRI) factors to the ABCD(2) tool. Read More on PubMed
  • Early studies suggested interactions between statins and clopidogrel. Based on the outcome and platelet data, there is now huge evidence of no interactions between statins and 75 to 300 mg clopidogrel; however, data with 600-mg loading are lacking. In a pre-specified analysis of the EXCELSIOR cohort, we investigated the interaction between statins, especially cytochrome P4503A4-metabolized atorvastatin and simvastatin, and the antiplatelet effects of a 600-mg loading dose of clopidogrel. We analyzed 1,395 patients scheduled for coronary angiography (CA). Patients received clopidogrel 600 mg at least two hours before CA and 75 mg daily thereafter in case of percutaneous coronary intervention (PCI). Statin medication on admission was continued unaltered until discharge. Platelet function was assessed by optical aggregometry and flow cytometry of adenosine diphosphate (ADP)-stimulated surface expression of CD62P, CD63 and PAC-1 before clopidogrel and immediately before CA. Residual platelet aggregation (RPA) after addition of ADP 5 muM was similar irrespective of statin treatment at baseline (p = 0.968). RPA at CA was 46.2 +/- 16.8% in patients without statin (n = 682), 45.5 +/- 17.0% in patients with atorvastatin (n = 255), 45.8 +/- 16.3% with simvastatin (n = 335), 47.3 +/- 14.9% with fluvastatin (n = 42) and 45.9 +/- 16.2% with pravastatin (n = 81; p = 0.962). Consistent results were obtained by flow cytometry. In patients with PCI (n = 553), the one-year incidence of death, myocardial infarction and target lesion reintervention did not differ between cohorts stratified according to statin co-medication (p = 0.645). Thus, peri-interventional atorvastatin and simvastatin had no effect on the antiplatelet activity of a loading dose of clopidogrel 600 mg and did not affect clinical outcome after PCI. Read More on PubMed
  • Recent observational studies suggest that the risk for stroke may be high in the first 90 days after transient ischemic attack (TIA). This finding may, however, not be consistent across existing studies assessing stroke risk after TIA. The objectives of our study were to conduct a systematic review and meta-analysis of observational studies estimating the risk of stroke at 2, 30, and 90 days after TIA and to explore clinical and methodological factors that may explain variability in findings across studies. Read More on PubMed
  • Stroke is often preceded by transient ischaemic attack (TIA), but studies of stroke risk after TIA are logistically difficult and have yielded conflicting results. However, reliable estimation of this risk is necessary for planning effective service provision, clinical trials, and public education. We therefore did a systematic review of all studies of stroke risk early after TIA. Read More on PubMed
  • Diagnosis and treatment of cerebral and retinal transient ischaemic attacks (TIAs) are often delayed by the lack of immediate access to a dedicated TIA clinic. We evaluated the effects of rapid assessment of patients with TIA on clinical decision making, length of hospital stay, and subsequent stroke rates. Read More on PubMed
  • Patients with transient ischaemic attack (TIA) or minor stroke are at high immediate risk of stroke. The optimum early treatment options for these patients are not known. Read More on PubMed
  • The risk of stroke in the week after a transient ischaemic attack or minor stroke is high and relatively predictable. Emergency investigation and treatment are justified. Read More on PubMed
  • The purpose of this study was to evaluate the potential impact of clopidogrel and statin interaction in a randomized, placebo-controlled trial with long-term follow-up. Read More on PubMed
  • To describe the epidemiology of U.S. emergency department (ED) visits for transient ischemic attack (TIA) and to measure rates of antiplatelet medication use, neuroimaging, and hospitalization during a ten-year time period. Read More on PubMed
  • There are no community-based studies on the incidence of transient ischemic attacks (TIAs) in Portugal. This study was designed to determine TIA incidence and the risk of stroke occurrence in rural and urban populations in northern Portugal. Read More on PubMed
  • We examined whether the presence of diffusion-weighted imaging (DWI) lesions and vessel occlusion on acute brain magnetic resonance images of minor stroke and transient ischemic attack patients predicted the occurrence of subsequent stroke and functional outcome. 120 transient ischemic attack or minor stroke (National Institutes of Health Stroke Scale < or = 3) patients were prospectively enrolled. All were examined within 12 hours and had a magnetic resonance scan within 24 hours. Overall, the 90-day risk for recurrent stroke was 11.7%. Patients with a DWI lesion were at greater risk for having a subsequent stroke than patients without and risk was greatest in the presence of vessel occlusion and a DWI lesion. The 90-day risk rates, adjusted for baseline characteristics, were 4.3% (no DWI lesion), 10.8% (DWI lesion but no vessel occlusion), and 32.6% (DWI lesion and vessel occlusion) (p = 0.02). The percentages of patients who were functionally dependent at 90 days in the three groups were 1.9%, 6.2%, and 21.0%, respectively (p = 0.04). The presence of a DWI lesion and a vessel occlusion on a magnetic resonance image among patients presenting acutely with a transient ischemic attack or minor stroke is predictive of an increased risk for future stroke and functional dependence. Read More on PubMed
  • Transient ischemic attacks (TIAs) have been shown to be a strong predictor of subsequent stroke and death. We present the incidence and short-term prognosis of TIA within a large population with a significant proportion of minorities with out-of-hospital TIA. Read More on PubMed
  • Transient ischemic attacks (TIAs) are warning signs of stroke. Recently, the hypothesis was raised that TIA bears a significant risk for death and dependence and requires the same complex diagnostic workup as a complete stroke. Read More on PubMed
  • Stroke risk after transient ischemic attack (TIA) has not been examined in an ethnically diverse population-based community setting. The purpose of this study was to identify stroke risk among TIA patients in a population-based cerebrovascular disease surveillance project. Read More on PubMed
  • The risk of stroke is elevated in the first 48 hours after TIA. Previous prognostic models suggest that diabetes mellitus, age, and clinical symptomatology predict stroke. The authors evaluated the magnitude of risk of stroke and predictors of stroke after TIA in an entire population over time. Read More on PubMed
  • The antiplatelet effect of clopidogrel may be attenuated by short-term coadministration of lipophilic statins. We investigated whether the coadministration of atorvastatin for 5 weeks in patients with acute coronary syndromes (ACS) could affect the antiplatelet potency of clopidogrel. Read More on PubMed
  • Canadian data on the characteristics, management and outcomes of patients with transient ischemic attack (TIA) are lacking. We studied prospectively a cohort of consecutive patients presenting with TIA to the emergency department of 4 regional stroke centres in Ontario. Read More on PubMed
  • Transient ischemic attacks (TIAs) often herald a stroke, but little is known about the acute natural history of TIAs. Our objective was to quantify the early risk of stroke after a TIA in patients with internal carotid artery disease. Read More on PubMed
  • To estimate the very early stroke risk after a transient ischaemic attack (TIA) or minor stroke and thereby inform the planning of effective stroke prevention services. Read More on PubMed
  • Statins primarily metabolized by cytochrome P450 3A4 (CYP3A4) reportedly reduce clopidogrel's metabolism to active metabolite, thus attenuating its inhibition of platelet aggregation ex vivo. However, the clinical impact of this interaction has not been evaluated. Read More on PubMed
  • The commonly quoted early risks of stroke after a first transient ischemic attack (TIA)-1% to 2% at 7 days and 2% to 4% at 1 month-are likely to be underestimates because of the delay before inclusion into previous studies and the exclusion of patients who had a stroke during this time. Therefore, it is uncertain how urgently TIA patients should be assessed. We used data from the Oxford Community Stroke Project (OCSP) to estimate the very early stroke risk after a TIA and investigated the potential effects of the delays before specialist assessment. Read More on PubMed
  • The risk of death or recurrent myocardial infarction (MI) in patients with chest pain and baseline isolated troponin elevation is unclear. To determine the early and short-term risk of death or MI associated with isolated troponin elevation across a spectrum of chest pain syndromes, we used baseline creatine kinase (CK)-MB and troponin data from the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) B troponin substudy, the Global Utilization of Strategies To Open Occluded Coronary Arteries (GUSTO) IIa troponin substudy, and the Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I (CHECKMATE) study. Patients were grouped into 1 of 4 categories based on marker status (troponin-positive/CK-MB-positive, troponin-positive/CK-MB-negative, troponin-negative/CK-MB-positive, or troponin-negative/CK-MB-negative). The adjusted odds of death or MI occurring at 24 hours and 30 days was assessed by baseline marker status using multivariable logistic regression, with the group negative for both markers used as the reference. Patients who were positive for both markers had the highest odds of the 24-hour and 30-day end point. The adjusted odds of the 30-day end point for patients with isolated troponin elevation were 1.3 (95% confidence interval 0.7 to 2.3) and 4.8 (95% confidence interval 1.4 to 16.0) for high- and low-risk patients, respectively. The risk for 24-hour and 30-day death or MI with isolated positive CK-MB results was lower than with isolated positive troponin results, and it was not significantly greater than if the 2 markers were negative. For patients with high- and low-risk chest pain, baseline troponin elevation without CK-MB elevation was associated with increased risk for early and short-term adverse outcomes. This suggests that these patients should be admitted to the hospital and monitored in either an intensive care or step-down unit. Read More on PubMed
  • The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm(3). The volume of first-ever ischemic stroke in the population is not known. Read More on PubMed
  • Management of patients with acute transient ischemic attack (TIA) varies widely, with some institutions admitting all patients and others proceeding with outpatient evaluations. Defining the short-term prognosis and risk factors for stroke after TIA may provide guidance in determining which patients need rapid evaluation. Read More on PubMed
  • It has recently been hypothesized that the figure of approximately half a million strokes substantially underestimates the actual annual stroke burden for the United States. The majority of previously reported studies on the epidemiology of stroke used relatively small and homogeneous population-based stroke registries. This study was designed to estimate the occurrence, incidence, and characteristics of total (first-ever and recurrent) stroke by using a large administrative claims database representative of all 1995 US inpatient discharges. Read More on PubMed
  • There is scant information available on the incidence of transient ischemic attack (TIA) in a defined population. This study defines incidence rates of first TIA and subtypes of TIA during 1985-1989 and compares the incidence to that obtained from a 1960-1972 cohort study. Read More on PubMed
  • In a community-based study of approximately 105,000 people, 184 presented with a transient ischemic attack during the 5 years between 1981 and 1986; we believe these persons represent almost all new cases of transient ischemic attack going to a doctor during that period. During a mean follow-up of 3.7 years 49 patients died, 45 had a first-ever stroke, and 17 had a myocardial infarction. Cardiac disease accounted for 17 (35%) deaths, while stroke was the cause of death in 15 patients (31%). The average actuarial risk of death was approximately 6.3%/yr, slightly greater than that expected for similar people without transient ischemic attacks (risk ratio [observed divided by expected] = 1.4). The actuarial risk of stroke was 11.6% during the first year after a transient ischemic attack and approximately 5.9%/yr over the first 5 years. Patients who suffered a transient ischemic attack had a 13-fold excess risk of stroke during the first year and a sevenfold excess risk over the first 7 years compared with people without transient ischemic attacks. The actuarial risk of death, stroke, or myocardial infarction over the first 5 years after a transient ischemic attack was approximately 8.4%/yr. The prognosis in this community-based cohort was better than that in previous reports. The high early risk of stroke means that investigation and treatment of new cases should commence as soon as possible. Read More on PubMed
  • In a randomized pilot study we compared the efficacy of temporary anticoagulation with intravenous heparin sodium to the efficacy of aspirin in preventing cerebral infarction in hospitalized patients with recent (less than 7 days) transient ischemic attacks (TIAs). Fifty-five patients (33 men, 22 women) aged 36-81 (mean 62.7) years met entry criteria and agreed to participate. Symptoms prompting hospitalization were referable to the carotid distribution in 43 patients (34 hemispheric, nine retinal); 12 patients had vertebrobasilar distribution TIAs. Twenty-seven patients received heparin and 28 received aspirin. Patients were treated until surgery or until long-term medical therapy was instituted, 3-9 (mean 5.5) days in the heparin group and 3-15 (mean 5.8) days in the aspirin group. Recurrent TIAs occurred in eight patients given heparin and in seven treated with aspirin. Infarction occurred in one patient in the heparin group and in four patients in the aspirin group (three brain, one retinal infarction). Initial symptoms in these five patients were referable to the carotid distribution in two and to the vertebrobasilar distribution in three. All patients but the one with a retinal infarction had recurrent TIAs prior to stroke. Our pilot study suggests that hospitalized patients with recent TIAs are at high risk for recurrent TIAs (15 of 55, 27%) and brain infarction (five of 55, 9%) and that patients with recent vertebrobasilar distribution TIAs have a marginally significantly higher risk (odds ratio 6.83, 95% confidence interval 0.65-88.66) of infarction than patients with recent carotid distribution TIAs. Read More on PubMed
  • Four hundred fifty-one patients with transient ischemic attacks (TIA) occurring within 1 month of hospitalization, admitted during 1977-1983, were analyzed to establish the effect on survival of age, race, sex, distribution of TIA, cigarette smoking, previous cerebral infarction or hemorrhage, previous TIA, or history of ischemic heart disease, valvular heart disease, cardiac dysrhythmia, hypertension, and diabetes mellitus. Proportional hazards analysis revealed that decreased survival was associated with increasing age, carotid artery distribution TIAs (compared with vertebrobasilar distribution TIAs), cigarette smoking, previous contralateral stroke, ischemic heart disease, and diabetes mellitus. We found great variation in the estimated survival of TIA patients, ranging from 5-year survivals of greater than 95% for 60-year-old patients with none of these risk factors to less than 25% for patients with all of these risk factors. Although the survival of the strata differed, the average mortality rates for this series of patients was about one-half of that observed for 225 patients accessed and followed by our center during 1961-1973. Read More on PubMed
  • We evaluated the efficacy of short-term intravenous heparin therapy in 74 patients with recent transient ischemic attacks (TIAs). The patients were treated after hospitalization until operation or long-term medical treatment was instituted. Heparin was given in a continuous infusion to maintain an activated partial thromboplastin time of 1 1/2 to 2 1/2 times control values. During the treatment period, 12 patients (16.2%) had recurrent TIAs and five (6.8%) had cerebral infarction. Bleeding complications occurred in nine patients (12.2%). In this limited series, heparin did not prevent recurrent TIAs or cerebral infarction among high-risk patients with recent TIAs. Read More on PubMed
  • This study analyzes 234 patients who recovered from an initial ischemic episode. The object was to see if the duration of the first episode influenced the chance of finding a treatable lesion or the chance of a further episode. The initial episodes varied from less than 5 minutes to longer than 3 weeks. There seemed to be no fundamental difference between transient ischemic attacks (TIAs) (less than 24 hours) and strokes which recover. However, 51% of those whose initial episode lasted less than 5 minutes had a subsequent stroke compared to 28% of those with an initial episode of more than 24 hours duration. Thirty percent of the former group who had angiograms had an operable lesion against 10% in the latter group. It seems that angiography has sufficiently high yield to be warranted in all patients where the initial attack lasted less than 30 minutes. In those with longer attacks the yield from angiography was much lower and noninvasive techniques should be considered in these patients, where available, prior to consideration for angiography. Investigation should be based on the degree of functional recovery and not on the arbitrary time division which normally divides TIAs and strokes. Bruits were the most reliable clinical indicators of stenosis. However the presence of intermittent claudication, hypertension and age over 50 were all more common in those with carotid stenosis. Read More on PubMed
  • Effective early management of patients with transient ischaemic attacks (TIA) is undermined by an inability to predict who is at highest early risk of stroke. Read More on PubMed

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