Comments on-Switching from vitamin K antagonist to dabigatran in atrial fibrillation: differences according to dose.

Abstract

We thank Vinding et al. for their evaluation of the Danish patients with atrial fibrillation, who were switched from vitamin K antagonists (VKA) to dabigatran etexilate. The authors evaluated data, from Danish national registries, for 1626 patients with atrial fibrillation who switched from VKA to dabigatran 110 mg or 150 mg, between 22 August 2011 and 31 December 2012. Among the VKA-experienced patients with atrial fibrillation, they found that one in four were switched to a dabigatran dose, contrary to the recommendations outlined in the European Society of Cardiology guidelines. There are some statements in the article that we would like to clarify. Vinding et al. state that in the RE-LY study of dabigatran 110 mg and 150 mg vs. warfarin, ‘Both doses reduced the risk of haemorrhagic stroke, but increased the risk of gastrointestinal bleedings’. They are correct that, compared with warfarin, 110 mg and 150 mg dabigatran reduced the risk of haemorrhagic stroke [relative risk (95% confidence interval (CI)) 0.31 (0.17–0.56), and 0.26 (0.14–0.49), respectively; P < 0.001 for both], and that 150 mg dabigatran increased the risk of gastrointestinal bleeding [relative risk (95% CI) 1.50 (1.19–1.89); P < 0.001]. However, the authors failed to note that 110 mg dabigatran did not increase the risk of gastrointestinal bleeding when compared with warfarin [relative risk (95% CI) 1.10 (0.86– 1.41); P = 0.43]. The authors also reported that ‘14% of patients were underdosed’. This statement is misleading, as there is no underdosing for dabigatran. The 110 mg dabigatran dose has been powerfully tested vs. warfarin, and in the RE-LY trial, showed non-inferiority for stroke prevention [relative risk (95% CI) 0.92 (0.74–1.13); P = 0.41] and superiority for the risk of major bleeding events [relative risk (95% CI) 0.80 (0.69–0.93); P = 0.003] compared with warfarin. While we acknowledge the authors’ definition of underdosing (‘patients switched to 110 mg without guideline criteria justifying this’), it would have been more accurate to have used ‘switched to a low dose incorrectly’ rather than use ‘underdosed’. We also consider that their statement ‘Since dabigatran was approved with specific guideline recommendations for dose reduction’ could be misread. We would like to clarify that the guidelines do not approve drugs, they provide recommendations on their use in clinical practice. The approval of both doses of dabigatran only occurs through regulatory and health authorities.