Antithrombotic Users Research Articles

Abstract TP293: Antithrombotic Therapy Does Not Increase Cerebral Microbleeding.

BACKGROUND: Antithrombotic drug users are at risk of intracerebral hemorrhage (ICH). Cerebral microbleeding (MB) is also a risk factor for ICH. Therefore, it is important to clarify the relationship between antithrombotic therapy (AT) and MB in order to prevent ICH. The incidence and number of MBs were evaluated in AT users and nonusers among consecutive acute ICH cases. We attempted to gain insights into the statistical“ black box” of hemorrhagic phenomena in which AT, MB, and ICH are mutually related. METHODS: T2*-weighted magnetic resonance imaging (1.5T MRI, 25 brain slices, 2-mm thick) was performed in 273 of 384 consecutive acute ICH (mean age 69.4yrs; M:F, 166:107) to evaluate the incidence and number of MBs, excluding the low-signal intensities associated with the hematoma lesions. RESULTS: Of the 273 cases , 86 (32%) cases were users and 187(68%) were nonusers, and MBs were detected in 60 (70%) users and 116 (62%) non-users. The incidence of MBs was comparable between users and nonusers (Chi-square independence test: χ2, 2.018 ; χ2(0.95)3.842; P = 0.155; odds ratio, 0.67129). The mean number of MBs was also not significantly different between users and nonusers [13.03 (median, 7) vs. 12.46 (median 7): t test: t -0.208; t (0.95) 1.653: P = 0.582]. CONCLUSION AT did not increase MB in this study patients, suggesting that this treatment does not contribute to vascular wall fragility. Complex phenomena leading to ICH were simply categorized into 3 steps: fragility of vascular wall, breakdown of vascular wall, and extension of hemorrhage. Antithrombotic therapy affects only the 3rd step and do not affect the 1st and the 2nd step, whereas hypertension affects all 3 steps. Therefore, in order to prevent hemorrhage extension and severe brain damage, stricter blood pressure control is required in antithrombotic drug users with MBs than in nonusers with MBs.

Cerebral Microbleeds on Magnetic Resonance Imaging and Anticoagulant-Associated Intracerebral Hemorrhage Risk

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.

Blood Pressure Levels and Bleeding Events During Antithrombotic Therapy

A prospective, multicenter, observational cohort study was conducted to clarify the association between major bleeding events and blood pressure (BP) levels during follow-up before development of bleeding events in antithrombotic users. A total of 4009 patients taking oral antithrombotic agents for cardiovascular or cerebrovascular diseases (2728 men, 69+/-10 years old) were followed. Changes in systolic and diastolic BPs between entry and the last clinic visit before intracranial hemorrhage (ICH) or extracranial hemorrhage were assessed. Over a median follow-up of 19 months, ICH developed in 31 patients and extracranial hemorrhage developed in 77. Entry BP levels were similar among patients with ICH, those with extracranial hemorrhage, and those without hemorrhagic events. Both systolic BP and diastolic BP were relatively high during follow-up as compared with the levels at entry in patients with ICH, whereas they showed plateaus in patients with extracranial hemorrhage and patients without hemorrhagic events. Average systolic BP levels between 1 and 6 months (hazard ratio, 1.45; 95% CI, 1.08 to 1.92 per 10-mm Hg increase) and between 7 and 12 months (hazard ratio, 1.47; 95% CI, 1.05 to 2.01) as well as average diastolic BP levels between 7 and 12 months (hazard ratio, 2.05; 95% CI, 1.15 to 3.62) were independently associated with development of ICH after adjustment for established ICH predictors. The optimal cutoff BP level to predict impending risk of ICH was >or=130/81 mm Hg using receiver operating characteristic curve analysis. An increase in BP levels during antithrombotic medication was positively associated with development of ICH, suggesting the importance of adequate BP control for avoiding ICH. BP levels did not appear to be associated with extracranial hemorrhage.