Evidence mounts to RE-LY on dabigatran

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Dabigatran etecxilate is a novel anti-coagulant that acts a direct thrombin inhibitor and provides stable anticoagulation at a fixed dose without any need for a laboratory control. In the RE-LY trial (Randomised Evaluation of Long-term Anticoagulation Therapy), dabigatran was shown to reduced strokes and peripheral embolic events in patients with atrial fibrillation when compared to warfarin; this superiority was seen at higher doses, although dabigatran was non-inferior at lower doses also. This analysis aimed to look at the main trial outcomes specifically in relation to each participating centre’s mean time in the therapeutic range (cTTR) in the warfarin population, which could have influenced patient outcomes.

In the RE-LY trial, 1 8113 patients at 951 sites were randomly assigned to 110 mg or 150 mg dabigatran twice daily versus warfarin dose adjusted to INR 2-3. The cTTR was estimated by averaging TTR for individual warfarin-treated patients calculated by the Rosendaal method. The outcomes of the trail were then compared across quartiles of cTTR.

No significant interactions were seen between cTTR and prevention of stroke and systemic embolism with either low (p=0.89) or high dose (p=0.2). Similarly, no significant interactions were seen with low- or high-dose dabigatran versus warfarin with regards to intracranial bleeding. Rates of major bleeding were lower with low-dose dabigatran 110 mg than with warfarin irrespective of cTTR, however when comparing high-dose dabigatran with warfarin a significant interaction was seen between cTTR and major bleeding (p=0.03). Similar rates of the composite outcome of all cardiovascular events and total mortality were seen at high cTTR, but not at low cTTR (see figure 1).

Time to primary outcome in centres with the worst international normalised ratio control (<57.1% of the time in the target range). Republished with permission from The Lancet.
Time to primary outcome in centres with the worst international normalised ratio control (<57.1% of the time in the target range). Republished with permission from The Lancet.

Conclusions

This analysis of the data from the RE-LY trial confirms the benefits of dabigatran were consistent regardless of the participating centres’ quality of INR control, although the advantages of dabigatran were greater at sites with poor INR control.

▶ Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010. doi:10.1016/S0140-6736(10)61194-4.

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