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

Abstract

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.

Methods: 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).

Results: 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).

Conclusions: 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.

Figure 1. Kaplan-Meier curves for the primary efficacy outcome of any stroke

Kaplan-Meier curves showing the time to the primary efficacy outcome event (any stroke) in patients with and without ICAS, treated with clopidogrel plus aspirin, or placebo plus aspirin. ICAS = intracranial arterial stenosis.

Figure 2. Forest plot for intention-to-treat analyses of the efficacy outcomes at 90 days

Intention-to-treat analyses showed no statistically significant treatment by presence of ICAS interaction on the effects of clopidogrel plus aspirin vs aspirin alone in the primary outcome of any stroke at 90 days (interaction p = 0.522), or other efficacy outcomes. Composite efficacy outcome indicated any new clinical vascular events including ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death. CI = confidence interval; HR = hazard ratio; ICAS = intracranial arterial stenosis; NA = not applicable.

Figure 3. Forest plot for on-treatment analyses of safety outcomes at 90 days

On-treatment analyses showed no statistically significant treatment by presence of ICAS interaction on the effects of clopidogrel plus aspirin vs aspirin alone on the safety outcome of any bleeding at 90 days (interaction p = 0.277), or other safety outcomes. CI = confidence interval; GUSTO = Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries; HR = hazard ratio; ICAS = intracranial arterial stenosis; NA = not applicable.