Dual Antiplatelet Therapy in Transient Ischemic Attack and Minor Stroke With Different Infarction Patterns: Subgroup Analysis of the CHANCE Randomized Clinical Trial

Abstract

Importance: Infarction patterns may serve as important imaging markers to assess the probability of stroke recurrence in transient ischemic attack (TIA) and minor stroke. However, it is unclear whether patients with different infarction patterns benefit differently from dual antiplatelet therapy.

Objectives: To investigate whether infarction patterns can stratify the risk of recurrent stroke and whether the efficacy and safety of clopidogrel plus aspirin vs aspirin alone are consistent in different infarction patterns after TIA or minor stroke.

Design, setting, and participants: In this prespecified imaging substudy of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) randomized clinical trial, a total of 1342 patients with noncardioembolic TIA or minor stroke at 45 sites of CHANCE from October 1, 2009, to July 30, 2012, were included in this substudy. The final analysis was conducted on July 30, 2016, and included 1089 patients with required magnetic resonance imaging sequences. Infarction patterns were grouped into multiple acute infarctions (MAIs), single acute infarction (SAI), and no acute infarction (NAI) according to diffusion-weighted imaging.

Main outcomes and measures: Primary and secondary efficacy outcomes were stroke recurrence and new clinical vascular event after 3 months, respectively. The safety outcome was moderate to severe bleeding risk after 3 months.

Results: Among 1089 patients, the mean (SD) age was 63.1 (10.7) years and 731 patients (65%) were men. Patients with MAIs (hazard ratio [HR], 5.8; 95% CI, 2.2-15.1; P < .001) and SAI (HR, 3.9; 95% CI, 1.5-10.5; P = .007) had higher risk of recurrent stroke than those with NAI after adjustment for potential confounders at 3-month follow-up. Stroke recurrence occurred in 15 (10.1%) and 25 (18.8%) of patients with MAIs administered clopidogrel plus aspirin and placebo plus aspirin, respectively (HR, 0.5; 95% CI, 0.3-0.96; P = .04), 24 (8.9%) and 24 (8.5%) of patients with SAI administered clopidogrel plus aspirin and placebo plus aspirin, respectively (HR, 1.1; 95% CI, 0.6-2.0; P = .71), and 3 (2.6%) and 2 (1.4%) of patients with NAI administered clopidogrel plus aspirin and placebo plus aspirin, respectively (HR, 1.7; 95% CI, 0.3-11.1; P = .56), with P = .04 for treatment × infarction pattern interaction effect. Clopidogrel plus aspirin did not increase moderate to severe bleeding risk.

Conclusions and relevance: Infarction patterns can efficiently stratify the risk of recurrent stroke within 3 months of noncardioembolic TIA or minor ischemic stroke. Patients with MAIs received the most pronounced clinical benefit from dual antiplatelet therapy without increasing the risk of moderate to severe bleeding. However, even if after dual antiplatelet treatment, patients with MAIs still had a risk of stroke recurrence as high as those with SAI.

Trial registration: clinicaltrials.gov Identifier: NCT00979589.

Figure 1.. Infarction Patterns of Multiple Acute Infarctions and Single Acute Infarction

Figure 2.. Stroke Recurrence Rates in Different Infarction Patterns for Patients With Transient Ischemic Attack and Minor Stroke

A, Kaplan-Meier curves showing the time to event for the primary efficacy outcome according to various infarction patterns (multiple acute infarctions [MAIs], single acute infarction [SAI], and no acute infarction [NAI]); B-D, Kaplan-Meier curves showing the time to event for the primary efficacy outcome in various antiplatelet therapy groups among distinct infarction patterns (MAIs, SAI, and NAI).