White matter hyperintensities and 90-day outcomes in patients with mild ischaemic stroke or high-risk TIA

BACKGROUND: Patients with large-artery atherosclerotic ischaemic stroke or high-risk transient ischaemic attack (TIA) often exhibit varying degrees of white matter hyperintensities (WMH), but the impact of WMH on the risk of stroke recurrence remains uncertain. We explored whether the burden of WMH increases the risk of bleeding and affects the efficacy of antiplatelet therapies in individuals experiencing mild ischaemic stroke or high-risk TIA. METHODS: This was a post hoc analysis of the intensive statin and antiplatelet therapy for high-risk intracranial or extracranial atherosclerosis trial, which was a double-blind, placebo-controlled, 2×2 factorial, and randomised clinical trial conducted at 222 centres in China. Patients were randomised to receive clopidogrel with aspirin or placebo. We rated WMH on baseline brain MRI Fazekas scores: mild WMH (Fazekas grade 0-2), moderate WMH (Fazekas grade 3-4) and severe WMH (Fazekas grade 5-6). The primary efficacy and safety outcomes were new stroke and moderate-to-severe bleeding within 90 days. RESULTS: We included 5454 patients (mean age: 64.0 years (SD, 9.5); 36.3% female), including 2681 with mild WMH, 1829 with moderate WMH and 944 with severe WMH. At 90 days, the rate of moderate-to-severe bleeding in patients with severe WMH was 1.6% (adjusted HR (aHR), 3.46 (95% CI 1.50 to 8.02)), compared with 0.5% in those with mild WMH (p=0.004). Haemorrhagic stroke occurred in 1% of patients with severe WMH (aHR, 5.95 (95% CI 1.72 to 20.62), p=0.005). However, we found no significant association with new stroke, and no interactions were observed between WMH severity and antiplatelet therapy. CONCLUSIONS: Severe WMH was associated with haemorrhagic stroke and bleeding events in patients with acute mild ischaemic stroke or high-risk TIA, with low absolute event rates and imprecise effect estimates; no evidence of interaction with antiplatelet therapy was observed. TRIAL REGISTRATION NUMBER: NCT03635749.