September 1, 2017Journal of Internal Medicine99 citationsOpen Access
Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study
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Key Result
Standard and reduced dose NOACs showed similar stroke risks in AF patients, but standard-dose rivaroxaban had a higher major bleeding risk (2.78%) compared to dabigatran (ARD -0.93%).
Key Points
- This research aims to compare the effectiveness and safety of standard and reduced doses of NOACs in patients with atrial fibrillation.
- Used Danish nationwide registries to include all oral anticoagulant-naïve AF patients initiating NOAC treatment from 2012 to 2016.
- Applied multiple Cox regressions to analyze stroke and bleeding risks.
- Calculated average treatment effects as 1-year standardized differences.
- 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% for standard doses and 2.51-2.78% for reduced doses.
- Rivaroxaban had a major bleeding risk of 2.78% (95% CI 2.42-3.17%) compared to dabigatran (-0.93%, 95% CI -1.45% to -0.38%) and apixaban (-0.54%, 95% CI -0.99% to -0.05%).
- Dabigatran showed a lower intracranial bleeding risk compared to rivaroxaban and apixaban.
Study Design
Type
Cohort (n=31,522)
Multicenter
Yes
Structured PICO
Does the choice of NOAC (dabigatran, rivaroxaban, apixaban) at standard or reduced doses affect the risk of stroke/thromboembolism and bleeding in oral anticoagulant-naïve patients with atrial fibrillation?
P
Population
31,522 oral anticoagulant-naïve patients with atrial fibrillation initiating NOAC treatment, evaluated for 1-year stroke and bleeding risks.
E
Exposure
Dabigatran, rivaroxaban, or apixaban at standard or reduced doses
C
Comparator
Direct comparisons between dabigatran, rivaroxaban, and apixaban at corresponding standard and reduced doses
O
Outcome
1-year standardized absolute risks of stroke/thromboembolism, major bleeding, and intracranial bleedinghard clinical
In a nationwide cohort of AF patients, standard and reduced doses of dabigatran, rivaroxaban, and apixaban showed similar effectiveness for stroke prevention, but rivaroxaban was associated with higher major bleeding risk.
Main Result
Absolute Risk Reduction: -0.93 (95% CI -1.45–-0.38)
Absolute Risk Reduction: -0.93%
Abstract
BACKGROUND: Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF). OBJECTIVE: We compared effectiveness and safety of standard and reduced dose NOAC in AF patients. METHODS: Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula). RESULTS: Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%). CONCLUSIONS: Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.
Cite This Study
Stærk et al. (2017) conducted a cohort in Atrial fibrillation (n=31,522). Non-vitamin K antagonist oral anticoagulants (dabigatran, rivaroxaban, apixaban) vs. Active comparators (head-to-head NOAC comparisons) was evaluated on Major bleeding (dabigatran vs rivaroxaban standard dose) (Absolute risk difference -0.93%, 95% CI -1.45 to -0.38). Standard and reduced dose NOACs showed similar stroke risks in AF patients, but standard-dose rivaroxaban had a higher major bleeding risk (2.78%) compared to dabigatran (ARD -0.93%).