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Cerebral Small Vessel Disease Burden for Bleeding Risk during Antithrombotic Therapy: Bleeding with Antithrombotic
Kanta Tanaka1, Kaori Miwa1, Masatoshi Koga1
1Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
Insights
Increased cerebral small vessel disease (SVD) burden significantly elevates the risk of major bleeding, including intracranial hemorrhage, in patients taking antithrombotic agents. SVD score predicts bleeding, guiding safer antithrombotic therapy.
Area of Science:
- Neurology
- Cardiovascular Medicine
- Radiology
Background:
- Cerebral small vessel disease (SVD) is common in patients with cerebrovascular or cardiovascular diseases.
- Antithrombotic agents are frequently prescribed for these patients, but carry a risk of bleeding.
- The relationship between SVD burden and antithrombotic-related bleeding risk requires further elucidation.
Purpose of the Study:
- To determine the excess risk of antithrombotic-related bleeding associated with cerebral small vessel disease (SVD) burden.
- To investigate the predictive value of SVD score for various bleeding events and ischemic events.
Main Methods:
- Observational, prospective cohort study involving 5,250 patients from 52 Japanese hospitals (2016-2019).
- Patients with cerebrovascular or cardiovascular diseases on oral antithrombotic agents were enrolled.
- Baseline multimodal MRI was used to calculate total SVD score; major bleeding was the primary outcome.
Main Results:
- A higher SVD score correlated with increased incidence rates of major bleeding (aHR for score 4 vs 0 = 5.47) and intracranial hemorrhage (aHR = 9.29).
- Significant increases in extracranial major bleeding (aHR = 3.43) and gastrointestinal bleeding (aHR = 2.54) were observed in patients with SVD score 4.
- Ischemic event rates also increased with higher SVD scores (aHR for score 4 vs 0 = 1.76).
Conclusions:
- Total SVD score is a significant predictor of intracranial hemorrhage and likely extracranial bleeding.
- Cerebral SVD burden is clinically relevant for assessing the safety of antithrombotic therapy.
- SVD assessment may aid in personalized antithrombotic treatment strategies to minimize bleeding risk.
Objective:
This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden.
Methods:
In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events.
Results:
Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0.
Interpretation:
Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787.
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