Physicians' Academy for Cardiovascular Education

Dabigatran 110 mg in VKA-naive patients with AF safe on the short term

Literature - Sørensen R, Gislason G, Torp-Pedersen C, et al. - BMJ Open. 2013 May 3;3(5)


Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study.

 
Sørensen R, Gislason G, Torp-Pedersen C, et al.
BMJ Open. 2013 May 3;3(5). doi: 10.1136/bmjopen-2013-002758
 

Background

The novel oral anticoagulant dabigatran has been studied in a large phase 3 randomised trial in patients with non-valvular atrium fibrillation (AF) and has been shown to be non-inferior to vitamin K antagonists (VKA) with a comparable or lower risk of strokes and a more favourable side-effects profile concerning bleeding [1]. Dabigatran has fewer interactions with food or other drugs and does not need monitoring of its anticoagulant effect, like is the case for VKA [2]. In addition, dabigatran 150 mg twice daily was superior to VKA in preventing stroke, and decreased mortality without increasing bleeding risk [1].
The approval of dabigatran for patients with non-valvular AF was followed by concerns about serious bleedings [3,4] and poor adherence to therapy [5]. Only preliminary real-life postapproval data on the use of dabigatran have been published.
This is a nationwide study aimed to describe use, comparative effectiveness and safety of treatment with dabigatran 110 and 150 mg twice daily among patients with AF, as compared to patients receiving VKA, during the initial 4 months after approval. Data were obtained from several individually linked Danish administrative registers. 52366 AF patients claimed a prescription for oral anticoagulation and were included in the study. 1612 (3.1%) and 1114 (2.1%) patients received dabigatran 110 and 150 mg twice daily respectively, and the rest was treated with VKA.
 

Main results

  • In comparison with people receiving VKA and dabigatran 110 mg, patients who were treated with dabigatran 150 mg were younger and had fewer comorbidities. 782 (48.5%) of the dabigatran 110 mg and 349 (31.3%) of the 150 mg group had previously used VKA.
  • 90.3% of patients treated with dabigatran 110 mg fulfilled the labelled recommendations by EMA. 55.5% of users of 150 mg fulfilled recommendations.
  • The adjusted risk of thromboembolism was higher among users of dabigatran as compared to warfarin, although when stratified by previous use of VKA, the increased risk of thromboembolism was only seen among previous VKA users (for both 110 and 150 mg). The adjusted risk of bleeding was increased among users of dabigatran 110 mg as compared to warfarin, which only persisted in previous users of VKA after stratification.
 

Conclusion

In 4 months after approval, already 5% of AF patients receives dabigatran for anticoagulant treatment. Off-label use with dabigatran 150 mg was common in this cohort.
The adjusted risk of thromboembolism in VKA naive dabigatran users was comparable to that seen in VKA users, but higher in dabigatran 110 mg users who previously used VKA. The adjusted bleeding risk in dabigatran  110 mg users who are VKA naive was comparable to VKA, but increased among patients who previously used VKA.
Although the short follow-up time and low number of events warrants cautious interpretation, dabigatran use in VKA naive patients seems a safe option, without increased risk of thromboembolic or bleeding events. These findings point at the need for a cautious approach when shifting high-risk patients from VKA to dabigatran treatment. Further real-life follow-up data of dabigatran use are needed.
 

References

1. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139–51.
2. Blech S, Ebner T, Ludwig-Schwellinger E, et al. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008;36:386–99.
3. Garber ST, Sivakumar W, Schmidt RH. Neurosurgical complications of direct thrombin inhibitors—catastrophic hemorrhage after mild traumatic brain injury in a patient receiving dabigatran. J Neurosurg
2012;116:1093–6.
4. Kernan L, Ito S, Shirazi F, et al. Fatal gastrointestinal hemorrhage after a single dose of dabigatran. Clin Toxicol 2012;50:571–3.
5. Salmela B, Joutsi-Korhonen L, Armstrong E, et al. Active online assessment of patients using new oral anticoagulants: bleeding risk, compliance, and coagulation analysis. Semin Thromb Hemost 2012;38:23–30.
 

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