Kevin O’Connor, MD
Oral anticoagulation is indicated for atrial fibrillation (AF) following cardioembolic stroke. When cerebral microbleeds (CMBs) are present, anticoagulated patients may have an increased risk of intracerebral hemorrhage (ICH). Choi et al. explored the impact of CMBs on the risk of major adverse cerebrovascular and cardiovascular events (MACCE) in ischemic stroke patients with AF on oral anticoagulation. They also examined the impact of choice of oral anticoagulant (OAC), whether vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC).
Among the 1742 patients with ischemic stroke and AF on oral anticoagulation, 393 (22.6%) had at least one CMB on admission gradient echo imaging. Patients were stratified by CMB presence, burden (1 [n=187], 2-4 [n=150], and ≥5 [n=56]), and location (lobar vs deep/mixed). Although the presence of a CMB increased risk of a MACCE (HR, 1.89 [95% CI, 1.23–2.88]; P=0.003), there was no significant increased risk when only one CMB was present (HR, 1.27 [95% CI, 0.66-2.44]; P=0.461). As the burden of CMBs increased, however, the risk of MACCE also increased for patients with 2-4 CMBs (HR, 2.08 [95% CI, 1.17-3.70]; P=0.012) and ≥ 5 CMBs (HR, 3.31 [95% CI, 1.62-6.78]; P=0.001). Risk of recurrent ischemic stroke was not significant unless there were ≥ 5 CMBs (HR, 2.97 [95% CI, 1.14-7.71]). The risk of ICH was significantly greater with at least 2 CMBs (HR, 8.07 [95% CI, 2.59-25.07]). There was no significant difference in the rate of MACCE based on CMB location, but strictly lobar CMBs had a higher risk of ICH (HR, 6.11 [95% CI, 2.07-18.03]).
Subjects on VKAs with CMBs had a higher risk of MACCE (adjusted HR, 2.12 [95% CI, 1.32–3.43]; P=0.002) compared to patients on a DOAC (adjusted HR, 1.42 [95% CI, 0.49–4.10]; P=0.517). The risk of recurrent ischemic stroke, ICH, and myocardial infarction were all significantly higher in patients receiving a VKA compared to patients receiving a DOAC. Analyses were adjusted for confounders including age, sex, hypertension, dyslipidemia, diabetes mellitus, current smoking, prior history of stroke or transient ischemic attack, initial NIHSS scores, reperfusion therapies, type of OACs, medication adherence, type of AF, diagnosis time of AF, and prior OAC therapy.
Although the study showed a correlation between increasing CMB burden and risk of MACCE, there was no difference based on location. CMB location, however, was only considered to be lobar or deep/mixed, and further study might elucidate a difference between lobar, deep, and mixed locations. While DOACs were associated with lower risk of MACCE, particular agents were not identified. Despite the risk of ICH in the setting of CMBs, use of oral anticoagulation remains indicated for AF following ischemic stroke as the risk of recurrent ischemic stroke would outweigh the risk of hemorrhage.
