Long-term Risk of Bleeding Events in Patients Taking Antithrombotic Agents for Cerebrovascular or Cardiovascular Disease.
Antithrombotic agents are essential for preventing cerebrovascular and cardiovascular diseases; however, bleeding complications remain a major concern, particularly among elderly patients and those receiving combination therapy.
We designed the Bleeding with Antithrombotic Therapy 2 (BAT2) Study, a prospective multicenter registry involving hospitals from a clinical research network in Japan, to clarify the risk of bleeding events in patients taking antithrombotic agents for cerebrovascular and cardiovascular diseases in recent clinical settings.
This prospective, multicenter, observational study followed bleeding and ischemic events for up to 2 years in patients with cerebrovascular and cardiovascular diseases. The primary outcome was major bleeding, and secondary outcomes included intracranial hemorrhage (ICH).
The 5,250 patients enrolled comprised 3,134 (70±11 years old; male, 66.6%; HASBLED ≥3, 32.8%) treated with single antiplatelet therapy (SAPT), 551 (71±11 years; 25.8%; 40.8%, respectively) with dual antiplatelet therapy (DAPT), 870 (75±10 years; 37.1%; 39.8%, respectively) with direct oral anticoagulant (DOAC) alone, 433 (72±12 years; 34.2%; 41.4%, respectively) with warfarin alone, 143 (76±8 years; 16.8%; 42.7%, respectively) with DOAC plus antiplatelet agents (AP); and 119 (73±12 years; 18.5%; 47.5%, respectively) with warfarin plus AP. During follow-up (median, 1.98 years), 93 patients experienced major bleeding and 55 developed ICH. Compared to the SAPT group (37 events, 0.63%/year), the DOAC (18 events, 1.12%/year; adjusted hazard ratio [aHR] 1.94, 95% confidence interval [CI] 1.09-3.46), warfarin (16 events, 2.02%/year; 3.44, 1.90-6.23), and DOAC plus AP groups (6 events, 2.24%/year; 3.07, 1.28-7.35) exhibited significantly higher risks of major bleeding after multivariable adjustment. DAPT (aHR 2.47, 95%CI 1.11-5.48), warfarin (5.38, 2.65-10.92), and DOAC plus AP (3.86, 1.30-11.47) had significantly higher risks of ICH than SAPT. The DAPT (2.28, 95%CI 1.65-3.14), DOAC plus AP (1.96, 1.08-3.56) and warfarin plus AP (2.83, 1.62-4.92) groups showed significantly higher risks of ischemic events compared to the SAPT group.
Oral anticoagulant alone and DOAC with antiplatelet therapy were associated with higher risks of major bleeding events than SAPT in long-term follow-up for patients with stroke and cardiovascular disease.Data access statement:The dataset of the BAT2 study is available to the investigators who participated in this study group upon submission of a reasonable study plan.
ClinicalTrials.gov (NCT02889653) and the University Hospital Medical Information Network clinical trial registry in Japan (UMIN 000023669).
We designed the Bleeding with Antithrombotic Therapy 2 (BAT2) Study, a prospective multicenter registry involving hospitals from a clinical research network in Japan, to clarify the risk of bleeding events in patients taking antithrombotic agents for cerebrovascular and cardiovascular diseases in recent clinical settings.
This prospective, multicenter, observational study followed bleeding and ischemic events for up to 2 years in patients with cerebrovascular and cardiovascular diseases. The primary outcome was major bleeding, and secondary outcomes included intracranial hemorrhage (ICH).
The 5,250 patients enrolled comprised 3,134 (70±11 years old; male, 66.6%; HASBLED ≥3, 32.8%) treated with single antiplatelet therapy (SAPT), 551 (71±11 years; 25.8%; 40.8%, respectively) with dual antiplatelet therapy (DAPT), 870 (75±10 years; 37.1%; 39.8%, respectively) with direct oral anticoagulant (DOAC) alone, 433 (72±12 years; 34.2%; 41.4%, respectively) with warfarin alone, 143 (76±8 years; 16.8%; 42.7%, respectively) with DOAC plus antiplatelet agents (AP); and 119 (73±12 years; 18.5%; 47.5%, respectively) with warfarin plus AP. During follow-up (median, 1.98 years), 93 patients experienced major bleeding and 55 developed ICH. Compared to the SAPT group (37 events, 0.63%/year), the DOAC (18 events, 1.12%/year; adjusted hazard ratio [aHR] 1.94, 95% confidence interval [CI] 1.09-3.46), warfarin (16 events, 2.02%/year; 3.44, 1.90-6.23), and DOAC plus AP groups (6 events, 2.24%/year; 3.07, 1.28-7.35) exhibited significantly higher risks of major bleeding after multivariable adjustment. DAPT (aHR 2.47, 95%CI 1.11-5.48), warfarin (5.38, 2.65-10.92), and DOAC plus AP (3.86, 1.30-11.47) had significantly higher risks of ICH than SAPT. The DAPT (2.28, 95%CI 1.65-3.14), DOAC plus AP (1.96, 1.08-3.56) and warfarin plus AP (2.83, 1.62-4.92) groups showed significantly higher risks of ischemic events compared to the SAPT group.
Oral anticoagulant alone and DOAC with antiplatelet therapy were associated with higher risks of major bleeding events than SAPT in long-term follow-up for patients with stroke and cardiovascular disease.Data access statement:The dataset of the BAT2 study is available to the investigators who participated in this study group upon submission of a reasonable study plan.
ClinicalTrials.gov (NCT02889653) and the University Hospital Medical Information Network clinical trial registry in Japan (UMIN 000023669).
Authors
Yoshimura Yoshimura, Miwa Miwa, Koga Koga, Tanaka Tanaka, Yagita Yagita, Nagakane Nagakane, Hoshino Hoshino, Terasaki Terasaki, Shiozawa Shiozawa, Iguchi Iguchi, Arakawa Arakawa, Fujimoto Fujimoto, Okada Okada, Ihara Ihara, Takahashi Takahashi, Doijiri Doijiri, Sasaki Sasaki, Yakushiji Yakushiji, Hirano Hirano, Toyoda Toyoda
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