The Increasing Bleeding Risk from Drug-drug Interactions in Patients with Direct Oral Anticoagulants

S.-M. Bang¹, J.Y. Lee¹, I.-Y. Oh¹, J.-H. Lee¹, S.-Y. Kim², S.-S. Kwon², H.-J. Yang², Y.-K. Kim²

¹Seoul National University Bundang Hospital, Department of Internal Medicine, Gyeonggi-do, Korea, Republic of, ²Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Department of Internal Medicine, Seoul, Korea, Republic of

Abstract Number: PB2456

Meeting: ISTH 2020 Congress

Theme: Venous Thromboembolism and Cardioembolism » VTE Treatment

Background: Drug-drug interactions (DDIs) are a concern for patients and providers, as polypharmacy is becoming more common in managing complex diseases or comorbidities. Direct oral anticoagulants (DOACs) have the potential for DDIs linked to increased bleeding.

Aims: This study evaluated the bleeding risk when the drugs of potential DDIs were simultaneously prescribed with DOACs.

Methods: From January 2014 to December 2016, We included new users of DOACs in patients with non-valvular atrial fibrillation (AF) and venous thromboembolism (VTE) and analyzed the actual rate of bleeding according to the number of drugs with potential DDIs. CHA₂DS₂-VASc score and Charlson Comorbidity Index (CCI) were assessed as covariates.

Results: Among 115,362 patient with AF or VTE who were newly administered DOACs (median age, 73 years [range,19-108]; men, 53.0%; AF, 81.9%; DOAC exposure: rivaroxaban, 48.7%; dabigatran 24.5%; apixaban 21.2%, and edoxaban,5.6%). A total of 7001 any bleeding (16.5%) and 2283 major bleeding (2.0%) events occurred with DOAC prescriptions. In multivariable logistic regression analysis showed that CHA₂DS₂-VASc score, CCI, and number of DDIs were significantly associated with bleeding events: as the score increased. In major bleeding events, CHA₂DS₂-VASc scores 4 or more (OR =2.35; 95% CI, 1.86-2.97, P < 0.0001], and number of DDIs with 2 or more prescribed medicines (OR = 3.73; 95% CI, 3.36-4.15, P < 0.000) were associated with significant increase in risk of major bleeding. The rates of exposure to DDI drugs in any bleeding and major bleeding were 56.7% and 66.1%, respectively. The most common drugs of DDIs showed the similar distributions; non-steroidal anti-inflammatory drugs, antiplatelet agents, diltiazem, amiodarone, and selective serotonin reuptake inhibitors were frequently prescribed.

Conclusions: Physicians prescribing DOAC medications for AF or VTE need to know the increasing bleeding risks associated with the number of DDIs drugs regardless of comorbidities.

To cite this abstract in AMA style:

Bang S-, Lee JY, Oh I-, Lee J-, Kim S-, Kwon S-, Yang H-, Kim Y-. The Increasing Bleeding Risk from Drug-drug Interactions in Patients with Direct Oral Anticoagulants [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-increasing-bleeding-risk-from-drug-drug-interactions-in-patients-with-direct-oral-anticoagulants/. Accessed October 1, 2023.

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