A study found that patients with AF who initiate therapy with standard dose dabigatran are at low risk of stroke and bleeding. Insights here.
A Danish study recently shed light on how novel oral anticoagulants (NOACs) are being used in clinical practice. The study, led by Jonas Bjerring Olesen, MD, of Copenhagen University (Denmark), was published in Thrombosis Research.1 The findings suggest that patients with atrial fibrillation (AF) who initiate therapy with standard dose dabigatran are at low risk of stroke and bleeding, and that doctors may be prescribing the drug in these relatively low-risk patients due to concerns over bleeding.
The advent of the NOACs dabigatran, rivaroxaban, apixaban, and edoxaban means that patients with AF now have more treatment options. Studies have shown that these agents are about as safe and as effective as the vitamin K antagonist, warfarin. However, few studies have evaluated how they’re being used in real world settings outside of clinical trials.
Researchers explored the issue by analyzing data from Danish national registries. The study included data from 53,860 patients with AF who initiated therapy at guideline-recommended doses with vitamin K antagonists (37.7%), dabigatran (24.4%), rivaroxaban (16.9%), or apixaban (21%) between 2011 and 2016. To evaluate trends over time, researchers used 2 scoring instruments: the CHA2DS2-VASc (to estimate stroke risk), and HAS-BLED (to estimate bleeding risk).
Results showed that, during most study years, patients who started on standard dose dabigatran (150 mg), had the lowest risk of stroke and bleeding. Moreover, the frequency of dabigatran initiators with past bleeding decreased over time. The authors suggest that these results might reflect concerns over bleeding in clinical practice, which could be related to findings from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Findings from the RE-LY trial suggest that standard dose dabigatran had higher rates of GI bleeding than warfarin.2
The study also found that reduced dosages of dabigatran (110 mg), rivaroxaban (15 mg), and apixaban (2.5 mg) were used preferentially in patients with higher risk of stroke and bleeding, compared with Vitamin K antagonists or standard dose NOACs. Patients prescribed reduced dose NOACs also appeared to have more comorbidities. Thus, the findings seemed to be consistent with Danish guidelines that recommend reduced dose NOACs in older patients with impaired kidney function.
In addition, results showed that patients who started on reduced dose apixaban were generally the oldest (mean age 75.1 years), and had the highest frequency of past stroke. While their risk of stroke was generally stable throughout the study, in 2016 they had the highest predicted risk of stroke.
The authors explained that these findings could have been influenced by the results and related marketing efforts from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, which found that apixaban was better than warfarin in preventing stroke and major bleeding.3
Finally, results showed that the risk of bleeding was similarly high for apixaban and rivaroxaban from 2013 through 2016.
The authors mentioned several limitations of the study. Because edoxaban had only been on the market for a short time when the study was started, the number of patients started on this drug was too small and they were not included in the analysis. Also, the study did not include AF patients treated solely by general practitioners, so the results may not generalize to these patients.
Take Home Points
• Danish registry study found that patients with AF who initiate therapy with standard dose dabigatran are at low risk of stroke and bleeding, and that doctors may be prescribing the drug in these relatively low-risk patients due to concerns over bleeding
• Reduced dosages of dabigatran, rivaroxaban, and apixaban were used preferentially in patients with higher risk of stroke and bleeding, compared to VKAs or standard dose NOACs, suggesting guideline-consistent care
• Patients who started on reduced dose apixaban were generally the oldest, and had the highest frequency of past stroke, suggesting doctors may be using this drug because of research suggesting superiority over warfarin in stroke prevention
1. Dukanovic A, Staerk L, FosbÃ¸l EL, et al. Predicted risk of stroke and bleeding and use of oral anticoagulants in atrial fibrillation: Danish nationwide temporal trends 2011-2016. Thromb Res. 2017;160:19-26.
2. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-1151.
3. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.