Dabigatran: Better for New Starts

Switching patients with atrial fibrillation (AFib) to dabigatran, instead of continuing warfarin, may increase their risk of myocardial infarction (MI) in the first 2 months of treatment, say researchers from Aalborg University in Aalborg and the Danish Health and Medicines Authority in Copenhagen, both in Denmark; and City Hospital in Birmingham, United Kingdom.

Using 3 nationwide Danish databases, the researchers identified 4,818 patients who were taking dabigatran for the first time (2,124 taking 110 mg, 2,694 taking 150 mg), and 8,133 patients taking warfarin for the first time. They also studied a second cohort of vitamin K antagonist (VKA)–experienced patients, of whom 1,554 were switched to dabigatran 110 mg and 1,825 switched to 150 mg, compared with 49,868 patients who continued on warfarin. Warfarin users were the highest-risk group in the VKA-naïve cohort, but the lowest-risk group in the VKA-experienced cohort. Mean follow-up time was 16 months.

Among the “new starters,” the analysis showed a nonsignificant trend to lower rates of MI with dabigatran for both doses, compared with warfarin. However, among the “switchers,” overall MI rates increased moderately for both dabigatran doses, and within 60 days of switching, an increased rate was “clearly significant,” the researchers say. In adjusted analyses, the early follow-up crude annual event rate was 3.19% among the 110-mg group and 2.01% among the 150-mg group, vs 0.82% among the warfarin group (110 mg hazard ratio [HR] 3.01, 95% confidence interval [CI], 1.48-6.10; 150 mg HR 2.97, 95% CI, 1.31-6.73).

In the sensitivity analysis, the 110-mg dose had a greater effect on the rate of MIs when patients with previous MIs were excluded. The researchers say this raises the possibility that dabigatran could be less protective against MI compared with warfarin, which may be explained by its weaker attenuation of thrombin generation.

In “real world” practice, the researchers note, clinicians may be more likely to switch problematic warfarin patients, such as those with poor adherence, difficulties in maintaining a high time in therapeutic range, or poor attendance at warfarin clinics, to one of the novel oral anticoagulants. (In this study, 79% of dabigatran users in the VKA-naïve cohort persisted with treatment after 3 months, compared with 89% of warfarin users. Similar numbers were seen in the VKA-experienced cohort.) Older patients with more comorbidity, the researchers add, may find it more difficult to attend for warfarin monitoring. The potential impact on MI in switchers needs to be balanced against the magnitude of benefit from stroke prevention, reduced intracranial hemorrhage, and lower vascular mortality. Still, they advise caution, especially when switching VKA-experienced patients with AFib.

Source
Larsen TB, Rasmussen LH, Gorst-Rasmussen A, et al. Am J Med. 2014;127(4):329-336.e4.
doi: 10.1016/j.amjmed.2013.12.005.