Key result
In a pharmacovigilance analysis, warfarin was associated with an increased probability of reporting haemorrhagic events compared to DOACs (ROR 2.85), while apixaban was associated with central nervous system haemorrhages (ROR 2.50).
Why the study?
Post-marketing data on DOAC risks are conflicting with few head-to-head comparisons, prompting evaluation of correspondence analysis as a pharmacovigilance tool to define the safety profiles of individual DOACs and warfarin.
Do direct oral anticoagulants and warfarin have different hemorrhagic safety profiles in patients reported to a pharmacovigilance database?
Observational (n=1,161)
Do direct oral anticoagulants and warfarin have different hemorrhagic safety profiles in patients reported to a pharmacovigilance database?
Effect estimate: ROR 2.85 (95% CI 2.18-3.73)
p-value: p=<0.05
In a real-world pharmacovigilance analysis, DOACs demonstrated distinct safety profiles, with apixaban unexpectedly showing a higher reporting odds ratio for central nervous system hemorrhages compared to other oral anticoagulants.
Introduction: Post-marketing data on the risks associated with direct oral anticoagulants (DOACs) are conflicting and only few studies evaluated a comparison between each different DOAC. Real-world data from pharmacovigilance databases can help to better define the safety profile of each DOAC and warfarin. However, Correspondence Analysis (CA) could represent a useful tool in this context. Objective: In the attempt to assess the usefulness of CA as a signal detection pharmacovigilance tool, we applied this method to the Italian Pharmacovigilance Database (RNF, Rete Nazionale di Farmacovigilanza ), by comparing with disproportionality analysis on warfarin and DOACs. Methods: Study based on AEs sent to RNF by Campania Region from 2008 to 2021, in which warfarin, dabigatran, apixaban, edoxaban or rivaroxaban were reported as suspected drug. AEs were clustered into three Standardized MedDRA Queries (SMQs): Central Nervous System Haemorrhages and Conditions (CNSH), GastroIntestinal Perforation, Ulceration, Obstruction or Haemorrhages (GIPUOH) and other Haemorrhages (HH). Non-haemorrhagic AEs were included in a fourth cluster (nHH). Results: We retrieved 1,161 reports: 41.5% are associated to warfarin, 21.0% to dabigatran, 17.8% to rivaroxaban, 13.9% to apixaban and 5.8% to edoxaban. No significant differences in age distribution were observed. Results of CA showed that dabigatran and warfarin have the highest contribution (44.910 and 47.656, respectively) to the inertia of Dimension 1 as well as apixaban and dabigatran to the inertia of Dimension 2 (53.768 and 30.488, respectively). Edoxaban and rivaroxaban showed a negligible total contribution. CA biplot showed positive associations between warfarin and HH, apixaban and CNSH and dabigatran and nHH. Conclusion: Results seem to confirm that DOACs are not interchangeable. Apixaban was surprisingly associated with a higher risk of cerebral haemorrhage. As expected, our data support the better safety profile of DOACs than warfarin in terms of skin and respiratory tract hemorrhagic risks. Finally, we showed how CA could play a complementary role in analyzing data from pharmacovigilance databases.
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Gaio et al. (2021) conducted an observational in Adverse events associated with oral anticoagulants (n=1,161). Direct Oral Anticoagulants (DOACs) vs. Warfarin was evaluated on Haemorrhage (HH) events (Warfarin vs DOACs) (ROR 2.85, 95% CI 2.18-3.73, p=<0.05). In a pharmacovigilance analysis, warfarin was associated with an increased probability of reporting haemorrhagic events compared to DOACs (ROR 2.85), while apixaban was associated with central nervous system haemorrhages (ROR 2.50).
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