Clopidogrel In High-Risk Patients With Acute Nondisabling Cerebrovascular Events Research Articles

Association of multiple infarctions and ICAS with outcomes of minor stroke and TIA.

To estimate the association of different patterns of infarction and intracranial arterial stenosis (ICAS) with the prognosis of acute minor ischemic stroke and TIA. We derived data from the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A total of 1,089 patients from 45 of 114 participating sites of the trial undergoing baseline MRI/angiography were included in this subgroup analysis. Patterns of infarction and ICAS were recorded for each individual. The primary efficacy outcome was an ischemic stroke at the 90-day follow-up. We assessed the associations between imaging patterns and prognosis of patients using multivariable Cox regression models. Among the 1,089 patients included in this subgroup analysis, 93 (8.5%) patients had a recurrent ischemic stroke at 90 days. Compared with those without infarction or ICAS, patients with single infarction with ICAS (11.9% vs 1.3%, hazard ratio [HR] 6.25, 95% confidence intervals [CIs] 1.40-27.86, p = 0.02) and single infarction without ICAS (6.8% vs 1.3%, HR 4.65, 95% CI 1.05-20.64, p = 0.04) were all associated with an increased risk of ischemic stroke at 90 days. Patients with both multiple infarctions and ICAS were associated with approximately 13-fold risk of ischemic stroke at 90 days (18.0% vs 1.3%, HR 13.14, 95% CI 2.96-58.36, p < 0.001). The presence of multiple infarctions and ICAS were both associated with an increased risk of 90-day ischemic stroke in patients with minor stroke or TIA, while the presence of both imaging features had a combined effect. NCT00979589.

Abstract WP420: Clopidogrel with Aspirin May be More Effective in Decreasing One-year Stroke Recurrence for Acute Minor Stroke with Watershed Infarcts: Subgroup Analysis of Chance

Background and Objective: In symptomatic cerebral large artery disease, watershed infarcts may result from hemodynamic impairment or microembolism. Such patients often have a high risk of recurrence or deterioration. It is still not clear whether dual antiplatelet therapy reduce the risk of stroke recurrence. The aim of this subgroup analysis is to discuss whether dual antiplatelet therapy could decrease the one year stroke recurrence more effectively for minor stroke patients with watershed infarcts. Methods: Patients enrolled in Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial and have magnetic resonance (MR) imaging data were included in this study. Diffusion-weighted imaging was obtained for detection of watershed infarcts. We assessed the interaction of the treatment effects of clopidogrel plus aspirin versus aspirin alone among patients with watershed infarcts or not. Results: Of the 1089 patients with MR imaging data enrolled in the CHANCE trial, 831 (76.3%) patients with acute infarcts. Among patients with acute infarcts, 93 (11.19%) were watershed infarcts, 55 (59.14%) received dual antiplatelet therapy. Patients with watershed infarcts had higher rates of recurrent stroke (17.20% vs 10.70%, p=0.063) at 1 year. For patients with watershed infarcts, one-year stroke recurrence was 6 (10.91%) in clopidogrel plus aspirin group and 10 (26.32%) in placebo plus aspirin group. There was interaction between antiplatelet therapy and presence of watershed infarcts on the primary outcome of any stroke (p=0.0933). (Kaplan-Meier curves were showed in the figure). Conclusions: For minor stroke patients with watershed infarcts, clopidogrel with aspirin may be more effective in decreasing 1-year stroke recurrence attributed to its potential mechanism of microembolism. Studies in other populations and subsequent analysis with adequate power are warranted to further verify such findings.

Abstract 1: Dual Antiplatelet Therapy is More Effective for Multiple Acute Infarcts: Subgroup Analysis of Chance

Background and Purpose: TIAregistry.org project showed that TIA and minor stroke patients with multiple acute infarctions (MAIs), which represent mechanisms of embolism, are at higher risk of recurrent stroke as compared to those with none or single acute infarction (SAI). We hypothesis that patient with MAIs may be more susceptible to dual antiplatelet therapy. Methods: We compared clopidogrel plus aspirin with aspirin alone with regard to their effectiveness and safety for prevention of stroke recurrence among non-cardiac TIA and minor ischemic stroke patients with different infarction patterns (no acute infarction, SAI, or MAIs) in the imaging subgroup from the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. The efficacy and safety outcome were stroke recurrence and moderate-to-severe bleeding event at 90 days respectively. Results: Overall, 1089 patients at 45 centers in CHANCE trial were included. The rate of recurrent stroke was 14.2%, 8.7%, and 2.0% in patients with MAIs, SAI and no infarction respectively at 90 days. Increased risk of stroke recurrence was observed in patients with MAIs (HR, 5.9; 95% CI, 2.3-15.2) and SAI (HR, 4.1; 95% CI, 1.6-10.7) (Figure A) as compared to those without infarction. The dual antiplatelet treatment was superior to aspirin alone for reducing the risk of recurrent stroke in patients with MAIs (HR 0.48; 95% CI, 0.25- 0.92; P = 0.03) but not in patients with SAI and without acute infarction with P=0.046 for interaction (Figure B-D). The effect of treatment assignment on bleeding did not vary among groups with different infarction patterns ( P &gt;0.05 for all). Conclusions: Patients with MAIs had the highest risk for stroke recurrence among patients with different infarction patterns. Patients with MAIs may benefit the most clinically from dual antiplatelet therapy and dual antiplatelet therapy does not increase the risk of hemorrhage among any groups.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack.

Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel. To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack. Three CYP2C19 major alleles (*2, *3, *17) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) randomized trial conducted from January 2, 2010, to March 20, 2012. Patients with acute minor ischemic stroke or transient ischemic attack in the trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. The primary efficacy outcome was new stroke. The secondary efficacy outcome was a composite of new composite vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death). Bleeding was the safety outcome. Among 2933 patients, 1948 (66.4%) were men, with a mean age of 62.4 years. Overall, 1207 patients (41.2%) were noncarriers and 1726 patients (58.8%) were carriers of loss-of-function alleles (*2, *3). After day 90 follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles (P = .02 for interaction; events among noncarriers, 41 [6.7%] with clopidogrel-aspirin vs 74 [12.4%] with aspirin; hazard ratio [HR], 0.51 [95% CI, 0.35-0.75]; events among carriers, 80 [9.4%] with clopidogrel-aspirin vs 94 [10.8%] with aspirin; HR, 0.93 [95% CI, 0.69 to 1.26]). Similar results were observed for the secondary composite efficacy outcome (noncarriers: 41 [6.7%] with clopidogrel-aspirin vs 75 [12.5%] with aspirin; HR, 0.50 [95% CI, 0.34-0.74]; carriers: 80 [9.4%] with clopidogrel-aspirin vs 95 [10.9%] with aspirin; HR, 0.92 [95% CI, 0.68-1.24]; P = .02 for interaction). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles (2.3% for carriers and 2.5% for noncarriers in the clopidogrel-aspirin group vs 1.4% for carriers and 1.7% for noncarriers in the aspirin only group; P = .78 for interaction). Among patients with minor ischemic stroke or transient ischemic attack, the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles. These findings support a role of CYP2C19 genotype in the efficacy of this treatment. clinicaltrials.gov Identifier: NCT00979589.

High-Sensitive C-Reactive Protein Predicts Recurrent Stroke and Poor Functional Outcome: Subanalysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events Trial.

Minor stroke and transient ischemic attack are common disorders with high rate of subsequent disabling stroke. We aim to investigate the role of high-sensitive C-reactive protein (hsCRP) in predicting recurrent stroke and poor functional outcome. In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, 3044 (59%) consecutive patients from 73 (64%) prespecified centers had hsCRP levels measured. The primary outcome was any stroke within 90 days. The secondary outcome included combined vascular events and dependence or death defined as modified Rankin Scale score of 2 to 6 at 90 days and a new vascular event during 1-year follow-up. The associations of hsCRP with recurrent stroke and functional outcome were analyzed by using Cox proportional hazards and logistic regression models. Elevated hsCRP (>3.0 mg/L) was observed in 32% of the study population. Patients with hsCRP >3 mg/L had an increased risk of recurrent stroke (adjusted hazard ratio, 1.46; 95% confidence interval, 1.08-1.98; P=0.039), ischemic stroke and combined vascular events, and poor functional outcome (adjusted odds ratio, 1.68; 95% confidence interval, 1.22-2.32; P=0.002) compared with those with hsCRP <1 mg/L within 90-day follow-up period. High hsCRP levels also independently predicted recurrent stroke during 1-year follow-up. There was no interaction of hsCRP levels with randomized antiplatelet therapy. High hsCRP levels predict recurrent stroke and poor functional outcome in acute patients with minor stroke or transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

Abstract 6: Treatment Effect of Clopidogrel Plus Aspirin Within 12 Hours of Acute Minor Stroke or TIA

Background and Purpose: The aim of this study was to analyze the benefits and safety associated with the combination therapy of clopidogrel and aspirin within 12 hours. Methods: This was a subanalysis of the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial, mainly limited to the prespecified group of patients presenting within 12 hours to either the combination of clopidogrel plus aspirin or aspirin alone. The primary outcome was ischemic stroke during 90-day follow-up. Results: Among 2573 patients randomized within 12 hours, 282 (10.96%) patients had ischemic stroke events. Among them, 113 (40.07%) occurred within 24 hours of symptom onset. Randomization within 12 hours was an independent predictor of ischemic stroke events (P=0.02). One hundred and fifty-eight (12.34%) of 1280 patients on aspirin experienced ischemic stroke compared to 124 (9.59%) of 1293 patients on clopidogrel-aspirin (P=0.02). The dual antiplatelet was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke (6.57% vs. 8.91%, P=0.03), but not progressive ischemic stroke (3.02% vs. 3.43%, P=0.28) (Table 1). There was no significant difference in hemorrhagic events (P=0.39). Conclusions: Among patients treated within 12 hours, the combination of clopidogrel and aspirin was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke during the 90-day follow-up and did not increase the hemorrhagic risk. The higher ischemic stroke rate in the initial hours after stroke supports early more aggressive antiplatelet therapy. Clinical Trial Registration-URL: http//www.clinicaltrials.gov . Unique identifier: NCT00979589.

Abstract WP347: Clopidogrel Plus Aspirin in Patients With Different Types of Single Small Subcortical Infarction_Subgroup Analysis of CHANCE Trial

Objective: We aim to investigate the effects and safety of clopidogrel plus aspirin in patients with different types of single small subcortical infarction(SSSI) in the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Methods: In this subgroup analysis, SSSI was defined as single DWI lesion of ≤2.0 cm and SSSI with stenosis of any degree of the parent artery was regarded as a SSSI+PAD. We assessed the interaction of the treatment effects of clopidogrel plus aspirin versus aspirin alone among patients with and without PAD. Efficacy was assessed by intention to treat analysis and safety was assessed in the on-treatment population. Results: A total of 338 patients with SSSI were included in the final analysis,105 with SSSI+PAD and 233 SSSI-PAD. In SSSI+PAD patients, 10.9% (5/46) had recurrent stroke in the clopidogrel-aspirin group as compared to 13.6% (8/59) in the aspirin group (adjusted hazard ratio, 0.66; 95% confidence interval, 0.20-2.20; P=0.50). In SSSI-PAD patients, 8.9% (11/124) had recurrent stroke in the clopidogrel-aspirin group as compared 7.3% (8/109) in the aspirin group (adjusted hazard ratio, 1.64; 95% confidence interval, 0.61- 4.38; P=0.32). The number of bleeding events was similar between the clopidogrel-aspirin group and aspirin group regardless of SSSI+PAD or SSSI-PAD. Conclusions: Although dual antiplatelet therapy did not significantly reduce the risk of recurrent stroke than aspirin alone in patients with SSSI. It was potentially beneficial to the patients with SSSI+PAD. Dual antiplatelet treatment did not increase the risk of bleeding in patients with any kind of SSSI.

Antithrombotic Therapy.

Symptomatic cerebral atherosclerosis including intracranial atherosclerosis (ICAS) is associated with a high risk of recurrent stroke. Antithrombotic agents are the mainstay of therapy in these patients. Several studies have found anticoagulation (warfarin) to increase the risk of bleeding events and have an efficacy no better than that of aspirin. Therefore, anticoagulants are not widely used unless patients develop recurrent ischemic symptoms despite receiving antiplatelet therapy. Because ICAS progression is not uncommon and the risk of stroke recurrence is high when aspirin monotherapy is used, dual antiplatelet agents may be needed at least in the early disease stage. The Trial of Cilostazol in Symptomatic Intracranial Stenosis (TOSS) found that aspirin plus cilostazol was significantly better than aspirin monotherapy in preventing progression (6.7 vs. 28.8%, p = 0.008). The TOSS II trial that compared aspirin plus cilostazol with aspirin plus clopidogrel found no significant difference in the progression rate (9.3% vs. 15.5%, p = 0.092). However, the overall changes in stenosis were more favorable (i.e., less progression and more regression) in the cilostazol group (p = 0.049). TOSS studies have limitations in that the end points were changes in magnetic resonance angiography results rather than clinical outcomes. Based on the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial results, and the fair outcome found in patients enrolled in the SAMMPRIS (Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis) trial, aspirin plus clopidogrel has been recommended in the early stage of symptomatic ICAS. However, the combination of aspirin and clopidogrel did not show superiority over aspirin monotherapy in ICAS patients in a recent CHANCE substudy. Considering that ICAS is the major pathology leading to stroke worldwide, further studies are needed to identify the best medication strategy in ICAS patients. Until then, physicians may choose appropriate antiplatelet agents after careful consideration of the characteristics of both the patients (i.e., degree of stenosis, stroke mechanism, risk of stroke, and risk of bleeding) and the antiplatelet agent (e.g., side effect, cost).

Dual antiplatelet therapy in stroke and ICAS: Subgroup analysis of CHANCE.

AB OBJECTIVE: We aimed to investigate whether the efficacy and safety of clopidogrel plus aspirin vs aspirin alone were consistent between patients with and without intracranial arterial stenosis (ICAS), in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the interaction of the treatment effects of the 2 antiplatelet therapies among patients with and without ICAS, identified by magnetic resonance angiography (MRA) in CHANCE (ClinicalTrials.gov identifier NCT00979589). Overall, 1,089 patients with MRA images available in CHANCE were included in this subanalysis, 608 patients (55.8%) with ICAS and 481 (44.2%) without. Patients with ICAS had higher rates of recurrent stroke (12.5% vs 5.4%; p<0.0001) at 90 days than those without. But there was no statistically significant treatment by presence of ICAS interaction on either the primary outcome of any stroke (hazard ratio for clopidogrel plus aspirin vs aspirin alone: 0.79 [0.47-1.32] vs 1.12 [0.56-2.25]; interaction p=0.522) or the safety outcome of any bleeding event (interaction p=0.277). The results indicated higher rate of recurrent stroke in minor stroke or high-risk TIA patients with ICAS than in those without. However, there was no significant difference in the response to the 2 antiplatelet therapies between patients with and without ICAS in the CHANCE trial. Classification of evidence: This study provides Class II evidence that for patients with acute minor stroke or TIA with and without ICAS identified by MRA, clopidogrel plus aspirin is not significantly different than aspirin alone in preventing recurrent stroke.

Association of Lp-PLA2-A and early recurrence of vascular events after TIA and minor stroke.

To determine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) measured in the acute period and the short-term risk of recurrent vascular events in patients with TIA or minor stroke. We measured Lp-PLA2 activity (Lp-PLA2-A) in a subset of 3,201 participants enrolled in the CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) trial. Participants with TIA or minor stroke were enrolled within 24 hours of symptom onset and randomized to single or dual antiplatelet therapy. In the current analysis, the primary outcome was defined as the composite of ischemic stroke, myocardial infarction, or death within 90 days. The composite endpoint occurred in 299 of 3,021 participants (9.9%). The population average Lp-PLA2-A level was 209 ± 59 nmol/min/mL (95% confidence interval [CI] 207-211). Older age, male sex, and current smoking were associated with higher Lp-PLA2-A levels. Lp-PLA2-A was significantly associated with the primary endpoint (adjusted hazard ratio 1.07, 95% CI 1.01-1.13 for every 30 nmol/min/mL increase). Similar results were seen for ischemic stroke alone. Adjustment for low-density lipoprotein cholesterol attenuated the association between Lp-PLA2-A and the primary endpoint (adjusted hazard ratio 1.04, 95% CI 0.97-1.11 for every 30 nmol/min/mL increase). Higher levels of Lp-PLA2-A in the acute period are associated with increased short-term risk of recurrent vascular events.

Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) Trial: One-Year Outcomes.

The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone, but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days). The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year follow-up. Differences in outcomes between groups were assessed by using the Cox proportional hazards model. Stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.006). Moderate or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin group and in 9 (0.4%) patients in the aspirin group (P=0.44). The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

Soluble CD40L Is a Useful Marker to Predict Future Strokes in Patients With Minor Stroke and Transient Ischemic Attack.

Elevated soluble CD40 ligand (sCD40L) was shown to be related to cardiovascular events, but the role of sCD40L in predicting recurrent stroke remains unclear. Baseline sCD40L levels were measured in 3044 consecutive patients with acute minor stroke and transient ischemic attack, who had previously been enrolled in the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Cox proportional-hazards model was used to assess the association of sCD40L with recurrent stroke. Patients in the top tertile of sCD40L levels had increased risk of recurrent stroke comparing with those in the bottom tertile, after adjusted for conventional confounding factors (hazard ratio, 1.49; 95% confidence interval, 1.11-2.00; P=0.008). The patients with elevated levels of both sCD40L and high-sensitive C-reactive protein also had increased risk of recurrent stroke (hazard ratio, 1.81; 95% confidence interval, 1.23-2.68; P=0.003). Elevated sCD40L levels independently predict recurrent stroke in patients with minor stroke and transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

Comment: TIA response to antiplatelets stratified by glycated albumin.

In the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) study of TIA, short-term combination therapy with clopidogrel and aspirin reduced recurrent stroke.1 Whether all TIAs benefit equally from this treatment remains unclear. Given that dual antiplatelet therapy also promotes hemorrhage, identifying which TIAs derive the greatest benefit would be clinically useful.

Recurrent stroke was associated with poor quality of life in patients with transient ischemic attack or minor stroke: finding from the CHANCE trial.

To examine the health-related quality of life (HRQOL) in patients with transient ischemic attack (TIA) or minor stroke and assess the impact of recurrent stroke on HRQOL. Health-related quality of life data on patients participated in the Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial were analyzed. The available 90-day EuroQoL data (EQ-5D) were used to calculate EQ-5D index score. Poor HRQOL was defined as an EQ-5D index score ≤0.5. The characteristics of HRQOL and factors predicting poor HRQOL in these patients were then explored. Among the total 5170 patients enrolled, 90-day HRQOL data were obtained from 5104 patients for analysis. The mean EQ-5D index score at day 90 was 0.88 ± 0.21 for all patients, but only 0.42 ± 0.35 for those with recurrent strokes. Poor 90-day HRQOL was found in 294 (5.8%) patients. Patients with poor HRQOL had more strokes during follow-up than patients with good HRQOL (94.9 vs. 4.7%, P < 0.001). Age, history of hypertension and diabetes, and NIHSS at baseline were independent risk factors for predicting poor HRQOL. Stroke recurrence, NIHSS at baseline, age, and minor stroke on admission became independent risk factors once stroke recurrence was added into the model. Stroke recurrence was associated with poor HRQOL in patients with TIA or minor strokes. Interventions focusing on controlling risk factors and prevention of worsening of neurological function may prevent poor HRQOL in these patients.

CHANCE Trial

The Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial tested the effect of early dual antiplatelet treatment for the prevention of secondary stroke within the first 90 days following a qualifying transient ischemic attack (TIA) or minor stroke in 5170 Chinese patients. The trial showed a significant reduction in secondary stroke in patients treated with dual antiplatelet therapy (hazard ratio, 0.68; 95% confidence interval, 0.57–0.81; P <0.001). There was no difference in the rate of moderate or severe hemorrhages (0.3% in both groups; P =0.73).1 CHANCE is critical support for early-onset and short-term intervention of antiplatelet therapy in patients with TIAs and mild strokes. The trial builds on knowledge gained during the past decade, beginning with observations that the risks of stroke early after a TIA or minor stroke are substantial,2–4 with a 2-day risk of stroke following TIA of ≈5%.2,4 Greater attention has since been paid to early evaluation, identification, and treatment of modifiable risk factors and the initiation of antiplatelet treatment for noncardioembolic events within 48 hours of the initial event.5 Previous lysis and recanalization studies have shown the importance of immediate medical management following ischemic events. More recently, studies have addressed the use of antiplatelet agents in an earlier time window, seeking to address the period of highest stroke recurrence risk. The Fast Assessment of Stroke and Transient Ischaemic Attack to Prevent Early Recurrence (FASTER) pilot trial randomized 392 patients with TIA/stroke presenting within 24 hours to aspirin plus clopidogrel or aspirin plus placebo. There was a reduction of stroke within 90 days seen with dual therapy (absolute risk reduction, 3.8%; 95% confidence interval, −9.4 to 1.9; P =0.19) and no significant difference in bleeding events between treatment arms.5 …

Combination Aspirin and Clopidogrel for Secondary Prevention of Ischemic Stroke

Though antiplatelet agents are the mainstay of antithrombotic therapy for secondary prevention of noncardioembolic cerebral ischemic events, the efficacy of combination aspirin and clopidogrel has yet to be clarified by clinical trials. Current evidence suggests that there is no role for long-term combination of aspirin/clopidogrel for secondary stroke prevention. Recent preliminary data from the CHANCE (Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events) trial suggests that stroke recurrence at 90days is reduced by a short course (21days) of combination aspirin/clopidogrel initiated within 24hours of minor stroke or TIA (Transient Ischemic Attack) compared with aspirin alone [1••] (Table1). Other ongoing trials, which are also investigating the role of short-term combination antiplatelet therapy initiated immediately after minor stroke and TIA, will determine if these findings will be replicated.