DOI: 10.1002/ana.26868 ISSN: 0364-5134

Cerebral small vessel disease burden for bleeding risk during antithrombotic therapy: Bleeding with Antithrombotic Therapy 2 study

Kanta Tanaka, Kaori Miwa, Masatoshi Koga, Sohei Yoshimura, Kenji Kamiyama, Yoshiki Yagita, Yoshinari Nagakane, Haruhiko Hoshino, Tadashi Terasaki, Yasushi Okada, Yusuke Yakushiji, Shinichi Takahashi, Toshihiro Ueda, Yasuhiro Hasegawa, Masayuki Shiozawa, Makoto Sasaki, Kohsuke Kudo, Jun Tanaka, Masashi Nishihara, Yoshitaka Yamaguchi, Kyohei Fujita, Yuko Honda, Hiroyuki Kawano, Toshihiro Ide, Takeshi Yoshimoto, Masafumi Ihara, Teruyuki Hirano, Kazunori Toyoda,
  • Neurology (clinical)
  • Neurology

Objective

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 MRI acquired under prespecified conditions were 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 5250 patients (1736 women; median age, 73 years; 9933 patient‐years of follow‐up), antiplatelets and anticoagulants were administered at baseline in 3948 and 1565, respectively. Median SVD score was 2 (interquartile range, 1‐3). Incidence rate of major bleeding was 0.39 (/100 person‐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 versus 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 than 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.

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