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Risk of Major Bleeding Associated with Concomitant Direct-Acting Oral Anticoagulant and Clopidogrel Use: A
Y Joseph Hwang1,2, Hsien-Yen Chang3,4, Thomas Metkus5
1Center for Drug Safety and Effectiveness, Johns Hopkins University, Baltimore, MD, USA. yhwang19@jhmi.edu.
Insights
Rivaroxaban and apixaban combined with clopidogrel showed similar major bleeding risks in US adults. Prior direct oral anticoagulant (DOAC) or clopidogrel monotherapy did not impact bleeding outcomes.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Research
Background:
- Combined anticoagulant-antiplatelet therapy is crucial for cardiovascular disease, atrial fibrillation, and venous thromboembolism.
- Assessing bleeding risks between rivaroxaban and apixaban when used with clopidogrel is essential for patient safety.
Purpose of the Study:
- To compare the risk of major bleeding between rivaroxaban plus clopidogrel and apixaban plus clopidogrel in US adults.
Main Methods:
- Retrospective cohort study of commercially insured US adults (2015-2018).
- Used propensity score-based inverse probability of treatment weighting (IPTW) to balance groups.
- Weighted Cox proportional hazards regression analyzed major bleeding risk.
Main Results:
- The study included 2895 rivaroxaban+clopidogrel users and 3628 apixaban+clopidogrel users.
- Rivaroxaban+clopidogrel had a similar risk of major bleeding compared to apixaban+clopidogrel (IPTW HR 1.13).
- Prior direct oral anticoagulant (DOAC) or clopidogrel monotherapy did not influence major bleeding risk.
Conclusions:
- Concomitant use of rivaroxaban+clopidogrel and apixaban+clopidogrel demonstrated a similar risk of major bleeding.
- The choice of DOAC or clopidogrel monotherapy prior to combined therapy did not affect bleeding risk.
Background And Aim:
Combined anticoagulant-antiplatelet therapy is often indicated in adults with cardiovascular disease and atrial fibrillation or venous thromboembolism. The study aim was to assess the comparative risk of bleeding between rivaroxaban and apixaban when combined with clopidogrel.
Methods:
We conducted a retrospective cohort study of commercially insured US adults newly treated with a combination of rivaroxaban+clopidogrel or apixaban+clopidogrel (2015-2018) using Merative™ Marketscan Research Databases. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the treatment groups. Weighted Cox proportional hazards regression was used to estimate the risk of major bleeding.
Results:
The study cohort included 2895 rivaroxaban+clopidogrel users and 3628 apixaban+clopidogrel users. The median (range) duration of follow up was 61 (73) days. Rivaroxaban+clopidogrel users had a similar risk of major bleeding compared with apixaban+clopidogrel users (IPTW incidence rate per 100 person-years 7.96 vs 7.38; IPTW hazard ratio [HR] 1.13 [95% CI 0.78-1.63]). In the subcohort of adults who were treated with DOAC or clopidogrel monotherapy prior to the combined therapy, the risk of major bleeding did not differ by the drug of monotherapy (IPTW HR for rivaroxaban+clopidogrel group: 0.66 [95% CI 0.33-1.32]; IPTW HR for apixaban+clopidogrel group: 1.10 [95% CI 0.55-2.23]) CONCLUSIONS: In our study of commercially insured US adults, the concomitant use of rivaroxaban+clopidogrel and apixaban+clopidogrel conferred a similar risk of major bleeding. DOAC versus clopidogrel monotherapy prior to the concomitant therapy did not influence the risk of major bleeding.
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