Thromboembolic Events While Taking Direct Oral Anticoagulants: An Analysis of Post-market WHO Database Reports from 2012 to 2020.

BACKGROUND AND OBJECTIVE

Several cases of venous thromboembolism in patients treated with direct oral anticoagulants (DOACs) have been reported in the literature, but a quantative analysis of postmarketing reports is lacking. The objective of this study was to determine the post-marketing odds ratio (OR) and reporting odds ratio (ROR) of venous thromboembolism in patients receiving DOACs compared among each other and to vitamin K antagonists (VKAs).

METHODS

The OR and ROR were used to determine the ratio of reports for deep vein thrombosis and pulmonary embolism between 1 January, 2012 and 15 November, 2020 using the World Health Organization VigiLyze database. This was performed using all venous thromboembolism events in which a DOAC or a VKA was the suspected medication. The OR and ROR including 95% confidence intervals were calculated for each DOAC drug in comparison to all VKAs as a group.

RESULTS

The OR of deep vein thrombosis was highest for rivaroxaban compared with dabigatran and apixaban [2.63 (2.41-2.89); 1.84 (1.72-1.97)]. The OR of deep vein thrombosis was lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.44 (0.32-0.61); 0.31 (0.22-0.42); 0.17 (0.12-0.23)]. The OR of pulmonary embolism was also highest for rivaroxaban compared with dabigatran and apixaban [2.59 (2.37-2.83); 1.79 (1.68-1.92)]. The OR of pulmonary embolism was also lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.77 (0.60-0.97); 0.59 (0.41-0.67); 0.30 (0.23-0.37)]. Comparing RORs of various DOACs with VKAs, rivaroxaban had the highest RORs for deep vein thrombosis/pulmonary embolism, in comparison to apixaban, dabigatran and edoxaban.

CONCLUSIONS

Our findings may indicate a higher association between rivaroxaban therapy and venous thromboembolism as compared with apixaban, dabigatran and edoxaban. These findings are uncertain owing to the reliability of a post-marketing registration system that is negatively influenced by a high level of under-reporting. However, based on pharmacodynamics, we cannot exclude the possibility that there is a real effect that may be driven by non-adherence.