Abstract
The increasing use of antithrombotic drugs in an aging population [including anticoagulants to prevent future ischemic stroke in individuals with atrial fibrillation (AF)] has been associated with a dramatic increase in the incidence of intracerebral hemorrhage (ICH) in users of antithrombotic drugs. Several lines of evidence suggest that cerebral small vessel disease (particularly sporadic cerebral amyloid angiopathy) is a risk factor for this rare but devastating complication of these commonly used treatments. Cerebral microbleeds (CMBs) have emerged as a key MRI marker of small vessel disease and a potentially powerful marker of future ICH risk, but adequately powered, high quality prospective studies of CMBs and ICH risk on anticoagulation are not available. Further data are urgently needed to determine how neuroimaging and other biomarkers may contribute to individualized risk prediction to make anticoagulation as safe and effective as possible. In this review we discuss the available evidence on cerebral small vessel disease and CMBs in the context of antithrombotic treatments, especially regarding their role as a predictor of future ICH risk after ischemic stroke, where risk-benefit judgments can be a major challenge for physicians. We will focus on patients with AF because these are frequently treated with anticoagulation. We briefly describe the rationale and design of a new prospective observational inception cohort study (Clinical Relevance of Microbleeds in Stroke; CROMIS-2) which investigates the value of MRI markers of small vessel disease (including CMBs) and genetic factors in assessing the risk of oral anticoagulation-associated ICH.
Highlights
AND SCOPE Over the last decade, increasing use of oral anticoagulants to prevent cardioembolic stroke due to atrial fibrillation (AF) in an aging population, has been associated with a fivefold increase in the incidence of anticoagulation-associated intracerebral hemorrhage (ICH; Flaherty et al, 2007) – a rare, but unpredictable and catastrophic complication
We focus on patients anticoagulated after ischemic stroke associated with AF, and describe the methods and rationale of a new prospective observational inception cohort study (CROMIS21) investigating the value of Magnetic resonance imaging (MRI) markers of small vessel disease and genetic factors, in assessing the risk of oral anticoagulation-associated ICH
RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) study was a non-inferiority trial of dabigatran versus warfarin; while the ICH rate was around 50–70% lower compared to warfarin, it is worth remembering that 50% of the participants were already taking warfarin (“warfarin survivors”) and patients with a recent ischemic stroke or TIA were excluded (Connolly et al, 2009)
Summary
AND SCOPE Over the last decade, increasing use of oral anticoagulants to prevent cardioembolic stroke due to atrial fibrillation (AF) in an aging population, has been associated with a fivefold increase in the incidence of anticoagulation-associated intracerebral hemorrhage (ICH; Flaherty et al, 2007) – a rare, but unpredictable and catastrophic complication. We focus on patients anticoagulated after ischemic stroke associated with AF, and describe the methods and rationale of a new prospective observational inception cohort study (CROMIS21) investigating the value of MRI markers of small vessel disease (including CMBs) and genetic factors, in assessing the risk of oral anticoagulation-associated ICH. RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) study was a non-inferiority trial of dabigatran versus warfarin (unlike earlier trials that established the superiority of warfarin over placebo); while the ICH rate was around 50–70% lower compared to warfarin, it is worth remembering that 50% of the participants were already taking warfarin (“warfarin survivors”) and patients with a recent ischemic stroke or TIA (within 14 days of randomization) were excluded (Connolly et al, 2009) These factors might have had an effect on the lower risk of anticoagulation-associated ICH observed. During follow-up, it was found that the risk of ICH increased significantly with the burden of CMBs: 0.6% in patients with no CMB, 1.9% in patients with one CMB, www.frontiersin.org
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