Antiplatelet Treatment After Transient Ischemic Attack and Ischemic Stroke in Patients With Cerebral Microbleeds in 2 Large Cohorts and an Updated Systematic Review

Abstract

Background and purpose: In patients with transient ischemic attack/ischemic stroke, microbleed burden predicts intracerebral hemorrhage (ICH), and ischemic stroke, but implications for antiplatelet treatment are uncertain. Previous cohort studies have had insufficient follow-up to assess the time course of risks, have not stratified risks by antithrombotic use, and have not reported extracranial bleeds or functional outcome of ICH versus ischemic stroke.

Methods: In 2 independent prospective cohorts with transient ischemic attack/ischemic stroke (Oxford Vascular Study/mainly white; University of Hong Kong/mainly Chinese), antiplatelet treatment was started routinely irrespective of microbleed burden. Risks, time course and outcome of ICH, extracranial bleeds, and recurrent ischemic events were determined and stratified by microbleed burden (0 versus 1, 2-4, and ≥5), adjusting for age, sex, and vascular risk factors.

Results: Microbleeds were more frequent in the Chinese cohort (450 of 1003 versus 165 of 1080; P<0.0001), but risk associations were similar during 7433 patient-years of follow-up. Among 1811 patients on antiplatelet drugs, risk of major extracranial bleeds was unrelated to microbleed burden (P_trend=0.87), but the 5-year risk of ICH was steeply related (P_trend<0.0001), with 11 of 15 (73%) of ICH in 140 of 1811 (7.7%) patients with ≥5 microbleeds. However, risk of ischemic stroke also increased with microbleed burden (P_trend=0.013), such that risk of ischemic stroke and coronary events exceeded ICH and major extracranial bleeds during the first year, even among patients with ≥5 microbleeds (11.6% versus 3.9%). However, this ratio changed over time, with risk of hemorrhage (11.2%) matching that of ischemic events (12.0%) after 1 year. Moreover, whereas the association between microbleed burden and risk of ischemic stroke was due mainly to nondisabling events (P_trend=0.007), the association with ICH was accounted for (P_trend<0.0001) by disabling/fatal events (≥5 microbleeds: 82% disabling/fatal ICH versus 40% disabling/fatal ischemic stroke; P=0.035).

Conclusions: In white and Chinese patients with ≥5 microbleeds, withholding antiplatelet drugs during the first year after transient ischemic attack/ischemic stroke may be inappropriate. However, the risk of ICH may outweigh any benefit thereafter.

Keywords: cerebral small vessel disease; magnetic resonance imaging; stroke; transient ischemic attack.

Figure 1.

Risk of recurrent stroke (A), recurrent ischemic stroke (B), intracerebral hemorrhage (C), and intracerebral hemorrhage and major extracranial bleeding (D) among patients with transient ischemic attack/ischemic stroke on antiplatelets.

Figure 2.

Risk of disabling or fatal (A) and nondisabling (B) ischemic stroke and intracerebral hemorrhage by microbleed burden in patients with transient ischemic attack/ischemic stroke on antiplatelets.

Figure 3.

Risk of ischemic and hemorrhagic events in transient ischemic attack/ischemic stroke patients with <5 and ≥5 microbleeds on antiplatelets, within 1 year of index event and between 1 and 5 years after index event. ICH indicates intracerebral hemorrhage.

Figure 4.

Pooled analyses of relative risk estimates from the current and previous studies showing risk of recurrent ischemic stroke (A) and of intracerebral hemorrhage (B) among patients with transient ischemic attack/ischemic stroke on antiplatelet agents with microbleeds vs those without, stratified by geographical origin, magnetic resonance imaging (MRI) scanner magnet strength, MRI sequence, and number of microbleeds. CI indicates confidence interval; GRE, gradient-recalled echo; HKU, University of Hong Kong; OXVASC, Oxford Vascular Study; RR, relative risk; and SWI, susceptibility weighted imaging.