Antiplatelet agents and randomized trials

Patients who have transient ischemic attack (TIA) or ischemic stroke are at a high risk of having a first or recurrent stroke. The annual risk is between 5% and 15%; the risk is highest in the first 48 hours following a TIA and highest in the first 7 days following an ischemic stroke. Secondary prevention includes antithrombotic therapy, treatment of risk factors, and interventional treatment of carotid stenosis. Antithrombotic options can include antiplatelet drugs such as aspirin, aspirin plus extended-release dipyridamole (ER-DP), clopidogrel, or clopidogrel plus aspirin. Oral anticoagulation is used in patients with a cardiac source of embolism such as atrial fibrillation. Aspirin monotherapy offers a modest risk reduction for recurrent stroke and for the combined endpoint of nonfatal stroke, myocardial infarction (MI), and vascular death. The combination of ER-DP and aspirin was shown to be superior to aspirin monotherapy in several trials. Clopidogrel is superior to aspirin in high-risk patients suffering from stroke, MI, or peripheral arterial disease. The combination of clopidogrel plus aspirin is not superior to aspirin or clopidogrel monotherapy and carries a significantly higher bleeding risk. The combination might offer benefit in short-term secondary prevention after TIA or stroke. Another ongoing trial is currently investigating the possible benefit and side effects of aspirin plus ER-DP versus clopidogrel in secondary stroke prevention.     

Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review

For patients with ischemic stroke or transient ischemic attack caused by atherothromboembolism, immediate and long-term aspirin reduces the relative risk of recurrent stroke, MI, and death attributable to vascular causes. Oral anticoagulation is not more effective than aspirin. Long-term clopidogrel reduces the relative risk of stroke, MI, or vascular death by about 9% (0.3% to 16.5%) compared with aspirin. Any long-term benefits of clopidogrel combined with aspirin, compared with aspirin or clopidogrel alone, appear to be offset by increased major bleeding. The combination of aspirin and extended-release dipyridamole reduces the relative odds of stroke, MI, or vascular death by about 18% (odds ratio 0.82, 0.74 to 0.91) compared with aspirin alone without causing more bleeding. Cilostazole reduces the risk of stroke, MI, or vascular death by 39% compared to placebo. A large clinical trial comparing clopidogrel with the combination of aspirin and dipyridamole, in >20 000 patients with recent (<120 days) atherothrombotic ischemic stroke, is expected to report in 2008. Emerging antiplatelet therapies presently being evaluated for secondary prevention of atherothromboembolism include other P(2)Y(12) ADP receptor antagonists (prasugrel, cangrelor, AZD 6140), thromboxane receptor antagonists (eg, S18886 - terutroban), and thrombin receptor (PAR-1) antagonists (eg, SCH530348).     

Results of the management of atherothrombosis with clopidogrel in high-risk patients trial: implications for the neurologist

The secondary prevention of ischemic stroke is aided by the use of antiplatelet therapy, and the predominant current choices are aspirin, aspirin plus extended-release dipyridamole, and clopidogrel. The potential utility of combining platelet antiaggregants with different mechanisms of action proved successful with aspirin plus extended-release dipyridamole, and this approach has been explored with the combination of clopidogrel and aspirin. In the Management of Atherothrombosis With Clopidogrel in High-Risk Patients trial, this combination was compared with clopidogrel alone for secondary prevention in patients with transient ischemic attack and stroke in a high-risk population with a high prevalence of other vascular risk factors. A nonsignificant trend for a reduction of the combined endpoint of ischemic stroke, myocardial infarction, vascular death, and rehospitalization was observed in the combination therapy group (P = .24). The frequency of serious, life-threatening bleeding adverse effects was almost doubled in the combination arm. Neurologists need to be aware of these results and avoid the use of clopidogrel plus aspirin in patients with stroke or transient ischemic attack until evidence that the combination is safe in this population is provided. Neurologists faced with patients who have had a stroke or transient ischemic attack and are receiving this combination of antiplatelet agents after coronary stenting should inform their cardiology colleagues of the reported bleeding risk, and they should encourage the use of the combination for as short a time period as possible after such coronary intervention.     

Ischemic stroke prevention: an update on antiplatelet therapy

Stroke is the third leading cause of mortality in the United States. As the leading cause of neurological deficits worldwide, stroke is associated with tremendous costs both to society and to the individuals and families stroke impacts. Antiplatelet agents have demonstrated efficacy in preventing recurrent atherothrombotic strokes and are the principal pharmacologic modality employed. With the recent development of the thienopyridines and the resurgence of dipyridamole, recommendations for antiplatelet therapy have undergone several iterations over the past decade. The focus of this review is to provide an update on the individual antiplatelet agents and recapitulate the current guidelines for antiplatelet selection and use in either transient ischemic attack or noncardiogenic ischemic stroke patients. Mechanisms of action, demonstrated efficacy, adverse effect profiles, and current consensus recommendations are reviewed for four conventional antiplatelet strategies, aspirin, ticlopidine, clopidogrel, and the combination of aspirin and extended-release dipyridamole.     

Antiplatelet Agents for Stroke Prevention

Stroke is one of the leading causes of disability and death. Ischemic stroke is a syndrome with heterogeneous mechanisms and multiple etiologies, rather than a singularly defined disease. Approximately one third of ischemic strokes are preceded by another cerebrovascular ischemic event. Stroke survivors are at high risk of vascular events (i.e., cerebrovascular and cardiovascular events), particularly during the first several months after the ischemic event. The use of antiplatelet agents remains the fundamental component of secondary stroke prevention. Based on the available data, antiplatelet agents should be used for patients with noncardioembolic stroke. The use of combination therapy (aspirin plus clopidogrel) has not been proven to be effective or safe to use for prevention of early stroke recurrence or in long-term treatment. There is no convincing evidence that any of the available antiplatelet agents are superior for a given stroke subtype. Currently, the uses of aspirin, clopidogrel, or aspirin combined with extended release dipyridamole are all valid alternatives after an ischemic stroke or transient ischemic attack. However, to maximize the effects of these agents, the treatment should be initiated as early as possible and be continued on a lifelong basis.     

The role of antiplatelet therapy in the management of ischemic stroke: implementation of guidelines in current practice

Abstract

Objective: To review and discuss evidence-based guideline recommendations for the use of antiplatelet agents for secondary prevention in patients with ischemic stroke or TIA.

Methods: A literature search was conducted on PubMed through August 2007 using combinations of the following search terms: aspirin, clopidogrel, dipyridamole plus aspirin, transient ischemic attack, secondary prevention, stroke and guidelines.

Results: Modification of risk factors such as hypertension, diabetes, hypercholesterolemia, cigarette smoking and obesity are fundamental to stroke management. Antiplatelet therapy is highly effective in reducing the risk of recurrent vascular events and is recommended over oral anticoagulants for non-cardioembolic stroke. Evidence from head-to-head comparative clinical trials versus aspirin monotherapy has shown that clopidogrel and the combination of aspirin plus dipyridamole are safe and effective therapeutic options.

Discussion: Despite the availability of evidence-based guidelines, recommended interventions are largely underutilized. Quality improvement initiatives such as the ASA's Get with the Guidelines – Stroke and the UCLA stroke PROTECT Program have demonstrated effectiveness in increasing adherence to recommended therapies and thereby improving patient outcomes.     

ESPRIT: is aspirin plus dipyridamole superior to aspirin alone in TIA or minor stroke patients?

Transient ischemic attack (TIA) or a (minor) ischemic stroke increases the risk of a recurrent stroke or death. Antiplatelet therapy with aspirin or clopidogrel is, in the absence of a potential cardiac embolic source, common practice to lower this risk. Until recently, adjuvant dipyridamole or low intensity oral anticoagulation were not generally prescribed in secondary prevention. In this article, we will summarize and discuss the published results of the European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT). In this trial, treatments with anticoagulants, aspirin alone and the combination of aspirin plus dipyridamole were compared, in a multicenter, three-armed, randomized, open-label study in patients with TIA or minor stroke.     

Antiplatelet therapy is effective in the prevention of stroke or death in women: subgroup analysis of the European stroke prevention study (ESPS)

Previous stroke prevention studies have suggested that the efficacy of antiplatelet therapy may be less in women than in men. This however, could be due to the small number of women in these trials and the low incidence of cases among female subjects. The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of dipyridamole 75 mg t.i.d and acetylsalicylic acid 330 mg t.i.d. to placebo in the secondary prevention of stroke or death after one or more recent attacks of TIA (transient ischemic attack), RIND (reversible ischemic neurological deficit) or stroke of atherothrombotic origin. From the 2500 patients recruited, 1307 patients were from a single center, Kuopio, East Finland. Forty-five percent of the patients were women. The number of end-point events (stroke or death from any cause) in women was one-third lower than that in men. End-point reduction in the treatment group was about 50% in women and about 40% in men, significantly lower than in the placebo group in both sexes. Thus, in the relatively randomly selected patient population from one Finnish center, a combination of dipyridamole and acetylsalicylic acid is as effective in women as in men in the prevention of stroke or death. It is unclear, however, whether this beneficial effect in both sexes is due to aspirin only or to the combination therapy of aspirin and dipyridamole.     

Ischemic stroke prevention: An update on antiplatelet therapy

Abstract

Stroke is the third leading cause of mortality in the United States. As the leading cause of neurological deficits worldwide, stroke is associated with tremendous costs both to society and to the individuals and families stroke impacts. Antiplatelet agents have demonstrated efficacy in preventing recurrent atherothrombotic strokes and are the principal pharmacologic modality employed. With the recent development of the thienopyridines and the resurgence of dipyridamole, recommendations for antiplatelet therapy have undergone several iterations over the past decade. The focus of this review is to provide an update on the individual antiplatelet agents and recapitulate the current guidelines for antiplatelet selection and use in either transient ischemic attack or noncardiogenic ischemic stroke patients. Mechanisms of action, demonstrated efficacy, adverse effect profiles, and current consensus recommendations are reviewed for four conventional antiplatelet strategies, aspirin, ticlopidine, clopidogrel, and the combination of aspirin and extended-release dipyridamole. [Neurol Res 2002; 24: 381-388]     

Stroke prevention: anti-platelet and anti-thrombolytic therapy

In patients with TIA or ischemic stroke of noncardiac origin antiplatelet drugs are able to decrease the risk of stroke by 11-15%, and the risk of stroke, MI, and vascular death by 15-22%, but not mortality. Low doses of aspirin (50-325 mg) are as effective as high doses and cause less gastrointestinal side effects. Severe bleeding complications are not dose-dependent. The combination of aspirin with slow release dipyridamole is superior to aspirin alone for stroke prevention. Ticlopidine is superior to aspirin but has slightly more serious adverse effects (neutropenia). It will be replaced by clopidgrel which has a better safety profile. Anticoagulation with an INR between 3.0 and 4.5 is too dangerous. Whether anticoagulation with lower INR is safe and effective is not yet known.     

Ongoing and planned trials of antiplatelet therapy in the acute and long-term management of patients with ischaemic brain syndromes: setting a new standard of care

Among high vascular risk patients, acetylsalicylic acid (ASA) reduces the relative risk of serious vascular events by about one fifth. However, because ASA fails to prevent four fifths of serious vascular events, more effective, yet equally safe and affordable, antiplatelet regimens are desired. Compared with ASA, clopidogrel alone reduces the odds of serious vascular events by about 10%, and the combination of dipyridamole and ASA reduces the odds of serious vascular events by about 6%. Combining ASA with an orally administered platelet glycoprotein (GP) IIb/IIIa blocker is not effective, and indeed more hazardous than ASA alone. Among patients with non-ST-segment acute coronary syndromes (ACS), the addition of an intravenously administered GP IIb/IIIa receptor antagonist to ASA reduces the risk of vascular events by about 10% compared with ASA, and the addition of clopidogrel to ASA reduces the risk of vascular events by 20% compared with ASA alone. Among patients undergoing percutaneous coronary intervention (PCI), both the addition of an intravenously administered GP IIb/IIIa receptor antagonist to ASA, and the addition of clopidogrel to ASA reduce the risk of vascular events by 30% compared with ASA alone. The greater efficacy of the combinations of ASA with clopidogrel, and ASA with an intravenously administered GP IIb/IIIa receptor antagonist, in patients with ACS and those undergoing PCI has fostered several ongoing and planned trials of these regimens in the acute and long-term management of patients with ischaemic brain syndromes. The combination of ASA and clopidogrel is being compared with ASA alone within 12 h of onset of symptoms of TIA in two trials (FASTER, ATARI), and the use of an intravenously administered GP IIb/IIIa receptor antagonist is being compared with placebo within 6 h of onset of acute ischaemic stroke in two trials (AbESST, AbESST-2). Six trials are assessing the combination of clopidogrel and ASA in the long-term management of patients with ischaemic brain syndromes due to atherothrombosis (MATCH, CHARISMA, ARCH, CARESS, SPS3) or atrial fibrillation (ACTIVE). The MATCH trial of clopidogrel and ASA versus clopidogrel alone in patients with recent TIA or ischaemic stroke is the first which is likely to report its results - in mid 2004. The combination of dipyridamole and ASA is being compared with ASA in the ESPRIT trial and with the combination of clopidogrel and ASA in the planned PRoFESS trial. These ongoing and planned clinical trials of antiplatelet therapy promise to further define the role of combination antiplatelet therapy in the acute and long-term management of patients with ischaemic brain syndromes.     

Antiplatelet drugs: how to select them and possibilities of combined treatment

Antiplatelets are the pivotal drugs in preventing recurrent stroke or other major vascular events in patients who have undergone TIA or stroke. Aspirin is the most widely used, although its effect is very modest (relative risk reduction 20%), and most physicians use between 100 and 325 mg daily as a maintenance dose. For patients who develop stroke on aspirin treatment, the options are either to increase the dose of aspirin or to administer another anti-aggregate. No study has yet been performed to support these approaches. In patients who cannot tolerate aspirin, the options are clopidogrel 75 mg once daily or dipyridamole 400 mg combined with 50 mg aspirin. An approach which is very appealing, but not yet proven is to combine different antiplatelet drugs with different modes of action, such as aspirin and clopidogrel, in order to achieve a better and more effective antithrombotic effect. Further controlled trials are needed to justify this approach.     

2012-2014年北京缺血性卒中患者阿司匹林和氯吡格雷联合使用率分析

目的 通过大数据分析我国临床缺血性卒中患者阿司匹林联合氯吡格雷（双抗）的使用率情况。
方法 从北京市职工医疗保险系统数据库中提取2012年1月-2014年12月,根据国际疾病分类
（International Classification of Diseases,ICD）-10编码主诊断为I63（缺血性卒中）和G45[短暂性脑缺血发
作（transient ischemic attack,TIA）和相关的综合征]的患者,以2013年6月为界限分为前后各18个月,比
较这两个阶段患者用药记录中阿司匹林联合氯吡格雷用药的使用比例。并按照主诊断为缺血性卒中
和TIA进行亚组分析。
结果 研究期间共纳入用药记录6 296 188例次,患者总计101 587例。2013年7月-2014年12月,每个
月双抗使用876.9例次（标准差129.8）,中位数867（最小值511、最大值1112）,占比14.7%。而2012年1
月-2013年6月每个月的双抗使用649.9例次（标准差129.8）,中位数650.5（最小值352、最大值895）,
占比12.3%。2013年6月以后,主诊断为缺血性卒中和TIA的患者每月双抗使用比例分别为20.2%和
11.1%,而2013年6月之前每月双抗的比例为14.5%和9.1%,2013年6月之后的双抗使用比例大于2013
年6月之前。2013年6月前双抗的使用人数占入选患者的18.3%,而2013年6月之后接受双抗治疗的患
者比例提高至22.2%。
结论 在北京市医疗保险缺血性卒中和TIA患者中,相比2013年6月前,2013年6月后使用阿司匹林联
合氯吡格雷进行双抗的比例较高。     

Dual Antiplatelet Therapy after Noncardioembolic Ischemic Stroke or Transient Ischemic Attack: Pros and Cons

Dual antiplatelet therapy simultaneously blocks different platelet activation pathways and might thus be more potent at inhibiting platelet activation and more effective at reducing major ischemic vascular events compared to antiplatelet monotherapy. Aspirin plus clopidogrel dual therapy is now the standard therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. However, dual antiplatelet therapy carries an increased risk of bleeding. Patients with ischemic stroke or transient ischemic attack (TIA) are generally older and likely to have a fragile cerebrovascular bed, which further increases the risk of systemic major bleeding events and intracranial hemorrhage. Clinical trials and meta-analyses suggest that in comparison to antiplatelet monotherapy, dual antiplatelet therapy initiated early after noncardioembolic ischemic stroke or TIA further reduces the rate of recurrent stroke and major vascular events without significantly increasing the rate of major bleeding events. In contrast, studies of long-term therapy in patients with noncardioembolic ischemic stroke or TIA have yielded inconsistent data regarding the benefit of dual antiplatelet therapy over monotherapy. However, the harm associated with major bleeding events, including intracranial hemorrhage, which is generally more disabling and more fatal than ischemic stroke, is likely to increase with dual antiplatelet therapy. Physicians should carefully assess the benefits and risks of dual antiplatelet therapy versus antiplatelet monotherapy when managing patients with ischemic stroke or TIA.     

Comparison of Antiplatelet Therapies for Prevention of Patent Foramen Ovale-Associated Stroke

AimsThe REDUCE study demonstrated a reduction in the risk of recurrent stroke with patent foramen ovale closure and antiplatelet therapy compared to antiplatelet therapy alone. The clinicians were allowed to choose among aspirin, clopidogrel, or aspirin/dipyridamole with the expectation that all antiplatelet therapies would have similar efficacy in this population. We tested that presumption by comparing recurrent stroke rates among antiplatelet agents within the control arm of the trial.MethodsWe evaluated patients in REDUCE study who were randomized to the medical arm. The primary endpoint for this analysis was freedom from clinical ischemic stroke through at least 2 years of follow-up, to a maximum of 5 years. In the primary analysis, antiplatelet treatment was defined as the agent during the week prior to a recurrent stroke or last known contact.ResultsOf 223 patients in the medical treatment arm, the initial agent was aspirin 52%, clopidogrel 30%, and aspirin/dipyridamole 12%. Patients treated with aspirin were similar to those treated with alternatives, but were more likely to be enrolled in the United States. The last reported agent was aspirin alone in 55%, clopidogrel alone in 31%, aspirin/dipyridamole in 7%, and other/nothing/missing in 7%. Recurrent stroke rates were similar for all 3 antiplatelet regimens in unadjusted and adjusted analyses, with no overall difference among agents (P= .17).ConclusionsAmong patients with patent foramen ovale-associated stroke who were managed medically, there were no differences among antiplatelet agents in the risk of recurrent stroke, though confidence intervals were wide.     

氯吡格雷联合阿司匹林治疗对轻型卒中与短暂性脑缺血发作患者功能预后的影响：CHANCE与POINT试验联合分析

目的 评价氯吡格雷联合阿司匹林双抗治疗对轻型缺血性卒中与TIA患者功能预后的影响。 方法 提取CHANCE和POINT试验所有的个体数据。这两项试验中,所有纳入患者在症状发作12 h （POINT）或24 h（CHANCE）以内随机接受氯吡格雷联用阿司匹林或单用阿司匹林治疗。结局指标为3个 月时功能预后不良（mRS≥2）,三等级定义卒中复发[致残性或致死性卒中复发（mRS≥2）、非致残性 卒中复发（mRS 0或1）、无卒中复发]。 结果 共10 013例患者纳入分析,其中来自CHANCE试验5132例（51.3%）,来自POINT试验4881例 （48.7%）;氯吡格雷联用阿司匹林组4995例（49.9%）,单用阿司匹林组5018例（50.1%）。氯吡格雷联 用阿司匹林组3个月时功能预后不良的患者比例低于单用阿司匹林组（11.6% vs 12.6%,校正OR 0.82, 95%CI 0.72～0.94,P =0.005）。氯吡格雷联用阿司匹林组致残性或致死性卒中复发（4.6% vs 6.1%, 校正OR 0.73,95%CI 0.61～0.87,P <0.001）、非致残性卒中复发（1.9% vs 3.0%,校正OR 0.62,95%CI 0.47～0.80,P <0.001）和卒中复发的整体致残性（校正cOR 0.70,95%CI 0.60～0.81,P <0.001）低于单 用阿司匹林组。 结论 与单用阿司匹林治疗相比,氯吡格雷联用阿司匹林治疗可进一步改善轻型缺血性卒中和TIA 患者3个月时功能预后,减少致残性卒中复发。     

Use of antiplatelet agents to prevent stroke: What is the role for combinations of medications?

Antiplatelet agents are the medications of choice for preventing non-cardioembolic strokes. The diverse pathways involved in platelet function suggest the possibility of synergistic effects by combining various agents. In heart disease and in the setting of coronary artery stents, antiplatelet therapy with clopidogrel and aspirin has established benefits. Although it is tempting to extrapolate the benefits of this combination for stroke prevention, recent clinical trials have not borne this out. Unacceptable bleeding risks without additional efficacy weigh against the routine use of clopidogrel with aspirin for stroke prophylaxis. The combination of aspirin and extended-release dipyridamole has demonstrated superiority over aspirin in two large secondary stroke prevention trials.     

The PRoFESS trial: future impact on secondary stroke prevention

Patients with transient ischemic attack and ischemic stroke have a high risk of recurrent stroke and death. While aspirin is accepted as standard therapy in these patients, recent trials demonstrate that a combination of aspirin and extended-release dipyridamole or clopidogrel is superior to aspirin monotherapy. Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers may also reduce recurrent stroke. The ongoing Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial is designed to evaluate whether extended-release dipyridamole plus aspirin compared with clopidogrel, and whether telmisartan in addition to usual care, in individuals after a stroke, will reduce the risk of further strokes. PRoFESS is a multicenter, randomized, double-blind trial involving 695 sites from 35 countries or regions. The primary outcome for the trial is recurrent stroke, using a time-to-event analysis. Safety is evaluated by assessing the risk of major hemorrhagic and other serious adverse events. With over 20,000 patients randomized, and utilizing a 2 x 2 factorial design, PRoFESS is the largest stroke trial to investigate the prevention of recurrent stroke.     

ESPRIT: The European/Australian stroke prevention in reversible ischaemia trial

The ESPRIT-trial addresses the problem that aspirin, the standard therapy for secondary prevention of vascular complications after a transient ischemic attack (TIA) or ischemic stroke of arterial origin, reduces the risk of serious vascular events by only about 13%. Anticoagulants may be an alternative, as these have proved highly efficacious in trials after myocardial infarction and after cerebral ischemia with atrial fibrillation. After cerebral ischemia of presumed arterial origin, high-intensity anticoagulation (INR 3.0-4.5) is not safe and low-intensity anticoagulation (mean INR 2.1) not more efficacious than aspirin, but the value of anticoagulation with an INR between 2.0 and 3.0 is still unknown. Secondly, a recent, large trial showed that the combination of aspirin and dipyridamole prevents more major vascular events than aspirin alone, but several earlier trials did not find such an advantage. In ESPRIT, patients with a TIA or minor ischemic stroke (Rankin grade≤3) will be randomized between oral anticoagulation (INR 2.0-3.0), the combination of dipyridamole (400 mg daily) plus aspirin (in any dose between 30 and 325 mg daily) and aspirin only. Primary outcome is the composite event ‘death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or major bleeding complication,’ whichever occurs first. Outcome assessment will be blinded. The recruitment of a total of 4,500 patients is planned. The trial started in July 1997. As of January 2003, about 2250 patients were included from 81 hospitals in 15 countries.     

Efficacy of dual antiplatelet therapy in cerebrovascular disease as demonstrated by a decline in microembolic signals. A report of eight cases

BACKGROUND: The presence of microembolic signals (MES) may indicate an increased risk of recurrent ischemic events in patients with stroke. The optimal management of such patients is uncertain. We report the effect of clopidogrel in addition to aspirin on the number of MES in a series of patients with ischemic stroke and transient ischemic attack (TIA) due to large-vessel disease. METHODS: 8 patients with either extracranial or intracranial artery stenosis were identified in 30-min MES studies by transcranial Doppler sonography as having MES. All patients were on antiplatelet therapy prior to baseline transcranial Doppler monitoring. The patients were subsequently treated with clopidogrel in addition to aspirin. Repeat MES studies were performed between day 3 and 7 with aspirin and clopidogrel. RESULTS: All patients were Chinese. The median interval time from symptom onset to initial MES study was 7 days (range of 2-30). MES donor sites included 4 severely stenosed or occluded internal carotid arteries and 4 stenosed middle cerebral arteries. The median MES number at baseline was 8 (range 3-51). Repeat MES studies showed a significant decrease in MES (p = 0.012, Wilcoxon signed ranks test). 4 patients had complete cessation of MES and all patients showed a decline in MES. No patient had recurrent strokes or bleeding complications. CONCLUSION: The rapid and significant decline of MES in our stroke and TIA patients suggests the possible efficacy of dual antiplatelet therapy with aspirin and clopidogrel in patients with MES and symptomatic large-artery occlusive disease. Randomized controlled trials should be conducted to confirm this preliminary observation.