Comparison of the effectiveness and safety of direct oral anticoagulants: a nationwide propensity score–weighted study

Arnar B. Ingason; Jóhann P. Hreinsson; Arnar S Ágústsson; Sigrún H. Lund; Edward Rumba; Daníel A. Pálsson; Indriði E. Reynisson; Brynja R. Guðmundsdóttir; Páll T. Önundarson; Einar S. Björnsson

doi:10.1182/bloodadvances.2022009099

December 23, 2022Blood AdvancesOpen Access

Comparison of the effectiveness and safety of direct oral anticoagulants: a nationwide propensity score–weighted study

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Why the study?

Randomized trials directly comparing different DOACs are nonexistent and previous observational studies have yielded conflicting results.

Does the choice of direct oral anticoagulant (apixaban, dabigatran, or rivaroxaban) affect the rates of stroke/systemic embolism and major bleeding in patients with atrial fibrillation?

Structured PICO

Does the choice of direct oral anticoagulant (apixaban, dabigatran, or rivaroxaban) affect the rates of stroke/systemic embolism and major bleeding in patients with atrial fibrillation?

P

Population

Patients with atrial fibrillation who are new users of apixaban, dabigatran, or rivaroxaban from 2014 to 2019 in a nationwide cohort.

I

Intervention

Direct oral anticoagulants (apixaban, dabigatran, or rivaroxaban)

C

Comparator

Active comparison among the three direct oral anticoagulants (apixaban, dabigatran, and rivaroxaban)

O

Outcome

Rates of any stroke or systemic embolism (stroke/SE) and major bleedinghard clinical

In patients with atrial fibrillation, stroke and systemic embolism rates are similar among DOACs, but rivaroxaban is associated with a higher risk of major bleeding compared to apixaban and dabigatran.

Implication

Apixaban was associated with lower major bleeding than other DOACs; leaves open need for RCTs before guiding choice.

Abstract

In the pivotal randomized controlled trials (RCTs) for patients with atrial fibrillation, direct oral anticoagulants (DOACs) had similar or even superior efficacy and safety compared with warfarin. However, RCTs comparing different DOACs are nonexistent and previous observational studies have yielded conflicting results. In this nationwide cohort study, rates of any stroke or systemic embolism (stroke/SE) and major bleeding were compared among new users of apixaban, dabigatran, and rivaroxaban with atrial fibrillation from 2014 to 2019. Inverse probability weighting was used to yield balanced study groups, and outcomes were compared using Cox regression. Stroke/SE rates were similar in patients receiving apixaban, dabigatran, and rivaroxaban. Dabigatran was associated with twofold higher rates of myocardial infarction (MI) than rivaroxaban (1.4 events/100 person-years (py) vs 0.7 events/100-py, hazard ratio [HR] 2.21, 95% confidence interval [CI], 1.00-4.90) and apixaban (1.4 events/100-py vs 0.7 events/100-py, HR 2.26, 95% CI, 0.90-5.67), although the second comparison included the possibility of a null effect. Rivaroxaban was associated with higher major bleeding rates compared with apixaban (2.9 events/100-py vs 1.8 events/100-py, HR 1.64, 95% CI, 1.13-2.37) and dabigatran (2.9 events/100-py vs 1.4 events/100-py, HR 2.18, 95% CI, 1.21-3.93). Specifically, rivaroxaban had higher rates of major gastrointestinal bleeding and other major bleeding than apixaban. In conclusion, although stroke/SE rates were similar for DOACs, rivaroxaban was associated with higher rates of major bleeding than other DOACs and lower rates of MI than dabigatran. These results may help guide oral anticoagulant selection, especially in patients at high risk of bleeding or MI.