Key result
Standard-dose DOACs are linked to ~33% lower risk of major bleeding versus phenprocoumon in AF.
Why the study?
DOACs were approved based on RCTs comparing them to warfarin, but in Germany phenprocoumon is almost exclusively used as the VKA, and RCTs with phenprocoumon are absent.
Do standard dose DOACs reduce thromboembolic events, major bleeding, and death compared to phenprocoumon in patients with atrial fibrillation?
Cohort (n=71,961)
Yes
Do standard dose DOACs reduce thromboembolic events, major bleeding, and death compared to phenprocoumon in patients with atrial fibrillation?
Hazard Ratio: 0.67 (95% CI 0.59–0.76)
Absolute Event Rate: 1.7% vs 4.05%
Absolute Risk Reduction: 1%
Number Needed to Treat: 101
p-value: p=<0.001
Standard-dose DOACs showed similar effectiveness to phenprocoumon in real-world AF patients, with lower bleeding risk for apixaban but a higher risk of death observed with rivaroxaban.
May favor standard-dose DOACs over phenprocoumon to reduce bleeding in AF; extends observational data but leaves open mortality signals.
OBJECTIVES: Direct oral anticoagulants (DOACs) were introduced based on randomised controlled trials (RCTs) comparing them to vitamin-K-antagonist (VKA) warfarin. In Germany, almost exclusively phenprocoumon is used as VKA. RCTs with phenprocoumon being absent we analysed the benefits and harms of DOACs and phenprocoumon for patients with atrial fibrillation (AF) in a real-world setting. DESIGN: In a retrospective observational cohort study, claims data covering inpatient and outpatient care from 2015 to 2019 were analysed by Cox regression and propensity score matching (PSM). SETTING: Data from a group of small-sized to medium-sized health insurance companies in Germany. PARTICIPANTS: We analysed datasets of 71 961 patients with AF and first prescription of phenprocoumon (n=20 179) or DOAC in standard dose (n=51 782). Patients with reduced dose of DOACs were excluded (n=21 724). OUTCOME MEASURES: Outcomes were thromboembolic events, major bleeding and death during a 12-month follow-up period. RESULTS: The regression analysis widely showed similarity between phenprocoumon and standard dose DOACs regarding effectiveness and safety. There were only three statistically significant differences: a lower bleeding risk with composite DOACs and apixaban (HR (95% CI) = 0.67 (0.59 to 0.76) and 0.54 (0.46 to 0.63), respectively) and a higher risk of death with rivaroxaban (1.21 (1.10 to 2.34)). The analysis after PSM was consistent with the first two results regarding composite DOACs and apixaban (number needed to treat, NNT 101 and 78) and showed a lower bleeding risk with rivaroxaban (NNT 156). Absolute differences were small. CONCLUSIONS: The small superiority or non-inferiority of DOACs over warfarin seen in the RCTs might not translate into relevant advantages of DOACs over phenprocoumon. To confirm the hypothesis, an RCT with phenprocoumon is needed. Next to the safety and effectiveness assessments other factors might also play a substantial role in the decision on the right OAC for stroke prevention.
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Warkentin et al. (2023) conducted a cohort in Atrial Fibrillation (n=71,961). Direct oral anticoagulants (DOACs) vs. Phenprocoumon was evaluated on Major bleeding (HR 0.67, 95% CI 0.59 to 0.76, p=<0.001). Standard-dose direct oral anticoagulants were associated with a significantly lower risk of major bleeding compared to phenprocoumon (HR 0.67) in patients with atrial fibrillation.
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