Clopidogrel Plus Aspirin Reduces Recurrent Stroke Risk in Patients With Multiple Acute Infarctions
Findings from the CHANCE trial demonstrated the benefit of clopidogrel plus aspirin vs treatment with aspirin alone in reducing risk of recurrent stroke.
Infarction patterns represent a feasible method for stratifying risk for recurrent stroke approximately 3 months following a minor ischemic stroke or noncardioembolic transient ischemic attack (TIA), according to an imaging substudy of the randomized, double-blind Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE; ClinicalTrials.gov Identifier: NCT00979589) clinical trial published in JAMA Neurology. Additionally, patients with multiple acute infarctions (MAIs) and TIA or minor ischemic stroke who are treated with clopidogrel plus aspirin experience a greater reduction in recurrent stroke compared with patients with no acute infarction (NAI) or single acute infarctions (SAIs).
In the substudy, investigators evaluated 1089 Chinese patients with noncardioembolic TIA or minor stroke from the CHANCE trial who were randomly assigned to receive either clopidogrel plus aspirin (n=531) or placebo plus aspirin (n=558). Participants underwent MRI examinations during hospitalization, with sequences including T1-weighted imaging, T2-weighted imaging, diffusion-weighted imaging (DWI), and 3-dimensional time-of-flight magnetic resonance angiography. Based on DWI, the investigators categorized infarction patterns as MAI (n=281), SAI (n=553), or NAI (n=255). Stroke recurrence and the occurrence of a new clinical vascular event after 3 months of treatment comprised the primary and secondary efficacy outcomes.
Compared with patients with NAI, investigators observed a significantly higher risk for recurrent stroke among patients with SAI (hazard ratio [HR], 3.9; 95% CI, 1.5-10.5; P =.007) and MAI (HR, 5.8; 95% CI, 2.2-15.1; P <.001) at 3 months. A greater proportion of stroke recurrence occurred among patients with MAI administered placebo plus aspirin vs clopidogrel plus aspirin (18.8% vs 10.1%, respectively; HR, 0.5; 95% CI, 0.3-0.96; P =.04).
Although crude analysis demonstrated that patients with MAI had higher 3-month stroke recurrence compared with those with SAI (HR, 1.7; 95% CI, 1.1-2.6; P =.02), there was no significant difference between these groups following adjustment for potential confounders (ie, demographics, time to randomization, medical history, medications, and Trial of Org 10172 in Acute Stroke Treatment [TOAST] classification) (HR, 1.4; 95% CI, 0.9-2.3; P =.13).
In terms of stroke recurrence, there were no differences between patients administered clopidogrel plus aspirin or placebo plus aspirin in the SAI (8.9% vs 8.5%, respectively; HR, 1.1; 95% CI, 0.6-2.0; P =.71) or NAI arm (2.6% vs 1.4%, respectively; HR, 1.7; 95% CI, 0.3-11.1; P =.56). There was, however, a significant interaction effect of treatment x infarction patterns (P =.04). At 3-month follow-up, only 2 moderate to severe bleeding events were reported in the placebo plus aspirin group, with no increased risk of severe bleeding among the clopidogrel-plus-aspirin arm.
The limited generalizability of the findings to demographics other than Chinese patients with TIA or minor stroke represents a potential limitation of the analysis.
Based on the findings, the investigators suggest that infarction patterns could provide an efficient means of stratifying “risk of recurrent stroke within 3 months of noncardioembolic TIA or minor ischemic stroke.”
Jing J, Meng X, Zhao X, et al. Dual antiplatelet therapy in transient ischemic attack and minor stroke with different infarction patterns: subgroup analysis of CHANCE randomized clinical trial [published online March 26, 2018]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.0247