#VisualAbstract: Microbleeds associated with increased risk of stroke

1. Microbleeds increase risk of intracerebral hemorrhage, ischemic stroke, recurrent stroke, and mortality.

2. Microbleeds do not appear to influence the effects of rivaroxaban treatment.

Evidence Rating Level: 2 (Good)

Cerebral microbleeds are known to be associated with intracerebral hemorrhage and recurrent. Questions have been raised related to antithrombitic treatment for those with a history of microbleeds and stroke. This international, double-blind, randomized, event-driven phase 3 clinical trial sought to investigate microbleeds in embolic strokes of undetermined source (ESUS) and how these relationships are impacted in the context of daily treatment with anticoagulant rivaroxaban 15mg compared to aspirin 100mg. This study included 459 stroke centers across 31 countries, including patients over the age of 50 years with imaging-confirmed ESUS between seven days and six months prior to screening. A total of 395 of the 3,699 participants had microbleeds on MRI (11%) and were included in subsequent analyses (M [SD] age = 69.5 [9.4] years, 39% female, 51% White). Several variables were independently associated with microbleeds, including occult intracerebral hemorrhage (OR = 5.23, 95% CI 2.76 to 9.90), hypertension (OR = 2.20, 95% CI 1.54 to 3.15), multiterritorial infarcts (OR = 1.95, 95% CI 1.42 to 2.67), chronic infarcts (OR = 1.78, 95% CI 1.42 to 2.23), East Asian race (OR = 1.57, 95% CI 1.04 to 2.37), and advancing age (OR = 1.03, 95% CI 1.01 to 1.04). Microbleed presence was associated with a four-fold risk of intracerebral hemorrhage (HR = 4.2, 95% CI 1.3 to 13.9) and 1.5-fold risk of recurrent stroke (HR = 1.5, 95% CI 1.0 to 2.3). Lobar-specific microbleeds were associated with a 2.5-fold risk of ischemic stroke (HR = 2.3, 95% CI 1.3 to 4.3) and all-cause mortality was increased by 200% (HR = 2.1, 95% CI 1.1 to 4.3). No evidence was found for interactions between microbleeds and treatment type for ischemic stroke, recurrent stroke, or all-cause mortality. Further, HRs of intracerebral hemorrhage on rivaroxaban were not significantly different between those with microbleeds (HR = 3.1, 95% CI 0.3 to 30.0) and those without (HR = 3.0, 95% CI 0.6 to 14.7, p>.99). This study demonstrates that microbleeds increase the risk of intracerebral hemorrhage, ischemic stroke, recurrent stroke, and mortality. However, microbleeds do not influence the effects of rivaroxaban treatment in the context of ESUS.

Click to read the study in JAMA Neurology

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