Safety first – Direct oral anticoagulants versus warfarin

By Carolin Beuker, MD, and Antje Schmidt-Pogoda, MD, Department of Neurology, Münster University Hospital

Oral anticoagulation is key to prevent stoke in patients with atrial fibrillation and systemic embolic events after for example hip or knee surgery in elderly patients. In the last years the new class of direct acting oral anticoagulants (DOACs) including dabigatran, rivaroxaban, edoxaban and apixaban, have become the “first-choice” over warfarin for many doctors.

Large randomized controlled trials of anticoagulants have shown the non-inferiority of DOACs compared with warfarin. Up until recently, there have been no antidotes for DOACs, and bleeding risk is therefore an ongoing safety concern. Idarucizumab is an approved antidote specific for dabigatran, but evidence from use in clinical practice is scarce.

In a paper recently published in the British Medical Journal, Vonpgradova reported findings from a prospective open-cohort study investigating the correlation between DOACs and risks of bleeding as compared with the relationship between warfarin and the same endpoints. Using data from two large United Kingdom primary care databases, between 2011 and 2016 a total of 196,061 anticoagulant users who had no anticoagulant prescriptions in the year prior to study entry were identified. Of these, 132,231 patients were taking warfarin, 7,744 dabigatran, 37,863 rivaroxaban, and 18,223 apixaban. All participants were subgrouped into 103,270 patients with AF (53%) and 92,791 without AF (47%). Edoxaban was excluded from the study because it was not licensed in the United Kingdom until the end of 2015.

The study outcomes were defined as major bleedings leading to hospital admission or death, ischemic stroke, venous thromboembolism, and all-cause mortality.

According to the results of this study, apixaban was associated with a decreased risk of major (particularly intracranial and gastrointestinal) bleeding events in patients with and without AF, both versus warfarin and versus rivaroxaban.

Rivaroxaban was associated with a decreased risk of intracranial bleeding in patients without AF compared with warfarin. Furthermore, the results of the study show that the use of dabigatran was associated with a lower risk of brain bleedings in patients with AF.

In contrast, rivaroxaban and low dose apixaban were both found to be associated with an increased all-cause mortality risk in patients with and without AF compared to warfarin. The authors suspect that this may reflect the closer monitoring of patients undergoing treatment with warfarin or may be related to unmeasured confounding due to prescribing choices related to underlying comorbidities.

The present study provides data indicating that in comparison to warfarin, DOACs are a reasonable choice with better safety profiles in both patients with and without AF. Therefore, the present data will be important in guiding physicians in considering DOACs as the preferred anticoagulant option. Further research is needed to identify patient groups that may not benefit from DOACs. Furthermore, new agents reversing anticoagulant effects of novel oral anticoagulants need to be developed.

Altogether, the study affirms the safety of DOACs in the clinical use in a real-world setting and provides evidence to support the use of DOACs in comparison to warfarin for prevention of stroke and systemic embolism.

Original Article: Vonpgradova Y, Coupland C, Hill T and Hippisley-Cox J. “Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care.” British Medical Journal. 2018 Jul 4;362:k2505.