Risk of Intracerebral Hemorrhage in Patients With Arterial Versus Cardiac Origin of Cerebral Ischemia on Aspirin or Placebo

Abstract

Background and Purpose— Patients who are anticoagulated after cerebral ischemia have a 19-fold-higher risk of intracerebral hemorrhage (ICH) if they had an arterial rather than a cardiac source. To determine whether this excess risk of ICH was due to the underlying disease (cerebral ischemia of arterial versus cardiac origin) or whether it depended on the antithrombotic regimen, we studied the risk of ICH in arterial versus cardiac origin of cerebral ischemia in patients who received aspirin or no antithrombotic drugs. Methods— Individual patient data of patients who received aspirin or placebo after cerebral ischemia were obtained from 9 clinical trials. Presence of atrial fibrillation was considered evidence of a cardiac source. Otherwise, events were considered of arterial origin. Cox proportional-hazards modeling was used for univariate and multivariate analyses. Results— Fifty-four ICHs occurred in 16 625 patient-years in the aspirin-treated patients, and 7 ICHs occurred in 4317 patient-years in those on placebo. After multivariate adjustment for age, sex, current smoking, history of hypertension and diabetes, and aspirin dose (aspirin-treated patients only), the hazard ratio for ICH in patients with an arterial versus a cardiac source was 0.74 (95% confidence interval, 0.30 to 1.82) for aspirin-treated patients and 4.34 (95% confidence interval, 0.35 to 54) for placebo-randomized patients. Conclusions— Our findings do not confirm the previous finding of an excess risk of ICH in patients with cerebral ischemia of arterial origin. Therefore, it seems that having cerebral ischemia of arterial origin by itself is not associated with an increased risk of ICH, but only in combination with high-intensity anticoagulation.