It has a rapid onset of action, with peak plasma concentration occurring 0. Pdf dabigatran or warfarin for the prevention of stroke. Hospital of cook county, department of internal medicine, chicago, il. Comparison of dabigatran, rivaroxaban, and apixaban for.
Dabigatran versus warfarin in patients with atrial. The primary objective of this post hoc analysis is to compare the outcomes of dabigatran at doses of 110 mg twice daily d110 and 150 mg twice daily d150 with those of warfarin in patients with and without vhd. To demonstrate noninferiority of blinded pradaxa 110 mg twice daily or 150 mg twice daily compared to openlabel warfarin inr target range 2. Dual antithrombotic therapy with dabigatran after pci in. However, the trial was terminated early when an interim analysis revealed more thromboembolic events and bleeding with dabigatran compared to warfarin. Population pharmacokinetic analysis of the oral thrombin. Results from rely and rely able key results from the rely trial the rely trial showed that dabigatran etexilate 150mg twice daily was superior to warfarin inr 23, median ttr 67%17 for stroke prevention in af. Randomized evaluation of longterm anticoagulant therapy rely. The key findings of this analysis of rely are the following. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation. Dabigatran versus warfarin in patients with atrial fibrillation re ly article in journal of the american college of cardiology 5512.
Efficacy and safety of dabigatran compared with warfarin at. Comparison of dabigatran and warfarin in patients with atrial. Nov 15, 2011 oldgren j, alings m, darius h, et al, on behalf of the rely investigators. Able patients continued to receive their originally assigned double.
Randomized evaluation of longterm anticoagulant therapy. In this noninferiority trial, we randomly assigned 18,1 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran 110 mg or 150 mg. In the rely trial, dabigatran was shown to be noninferior and then later updated showing superiority in reducing ischemic and hemorrhagic strokes relative to warfarin. Because dabigatran etexilate is a substrate of the p. Highlights of prescribing information these highlights do not include all the information needed to use pradaxa safely and effectively. Rely trial, dabigatran versus warfarin reduced both stroke and haemorrhage. In the era of the new anticoagulants, this landmark rct compared low 110 mg po bid and highdose 150 mg po bid dabigatran with doseadjusted warfarin in preventing stroke in at risk patients with atrial fibrillation. Backgroundtriple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention pci for. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation. The randomized evaluation of longterm anticoagulation therapy rely was a randomized trial designed to compare two fixed doses of dabigatran, each administered in a blinded manner. For 18 024 patients at 906 sites, the cttr was estimated by averaging ttr for individual warfarintreated patients calculated by the rosendaal method. The study should not impede other ongoing trials with direct thrombin inhibitors or factor xa inhibitors. Comparing our results with the rcts, 46 we did not find the reductions in stroke risk with dabigatran 150 mg and apixaban compared with warfarin that was shown in the rely and aristotle trials. Rely trial assessed the efficacy and safety of two fixed doses of dabigatran etexilate 110 or 150 mg twice a day, with adjusteddose warfarin targeted international normalized.
In the rely randomized evaluation of longterm anticoagulant th erapy study, a lifethreatening bleed bleeding that met one or more of the following criteria. Pradaxa dabigatran etexilate mesylate capsules, for oral use. The incidence of stroke was less with dabigatran 1. Efficacy and safety of dabigatran compared to warfarin at. Permanent discontinuation of therapy was defined as an interruption in dabigatran therapy 8 weeks.
Concomitant use of these drugs should be undertaken with caution. In the rely trial, 18 1 patients at 951 sites were randomly assigned to 110 mg or 150 mg dabigatran twice daily versus warfarin dose adjusted to inr 2030. Risks for stroke, bleeding, and death in patients with atrial. Rely was a phase iii,multicenter, prospective, randomized, openlabel,blinded, trial in 18,1 patients with nonvalvular af at risk of stroke. Apixaban vs warfarin in patients with atrial fibrillation 1. Executive summary dabigatran etexilate pradaxa has shown a consistent efficacy and safety profile in the prevention of stroke across a wide range of patients with atrial fibrillation af115 the rely trial investigated dabigatran etexilate in the prevention of stroke and systemic embolism in patients with nonvalvular af. Comparison of dabigatran and warfarin in patients with. In the randomized evaluation of longterm anticoagulant therapy rely trial, dabigatran 150 mg was shown to be superior to warfarin for. Cannon deepak l bhatt, jonas oldgren, gregory yh lip, stephen g ellis, takeshi kimura, michael maeng.
Cannon deepak l bhatt, jonas oldgren, gregory yh lip, stephen g ellis, takeshi kimura, michael maeng, bela merkely, uwe zeymer, savion gropper, matias nordaby, eva kleine, ruth harper, jenny. We aimed to investigate the primary and secondary outcomes of the rely trial in relation to each centres mean ttr cttr in the warfarin population. Methods in the rely trial, 18 1 patients at 951 sites were randomly assigned to 110 mg or 150 mg dabigatran twice. Center average ttr in the warfarin arm rosendaal method applied as a proxy for all patients in each center statistics. In a previous study of patients with af initiating warfarin or standarddose dabigatran treatment, using the same medicare database and outcome definitions as in this study, results similar to those of the rely trial were obtained, suggesting that adherence to the twicedaily dabigatran regimen by medicare beneficiaries was comparable to that. Pdf efficacy and safety of dabigatran versus warfarin. Published in 2009, the randomized evaluation of longterm anticoagulation therapy rely trial was a noninferiority study randomizing 18,000 patients with nonvalvular af and a moderatetohigh risk of thromboembolic stroke to either high or lowdose dabigatran or to warfarin. Dabigatran vs rivaroxaban for nonvalvular atrial fibrillation. Efficacy and safety of dabigatran versus warfarin from the re. Because dabigatran etexilate is a substrate of the pglycoprotein transport system, potent inhibitors or inducers are expected to alter plasma levels of dabigatran. The rely trial is a landmark study with regard to the management of patients with atrial fibrillation and thromboembolic risk.
The data from this post hoc analysis of cardioversion in the rely trial, which is the largest experience of cardioversion to date, are an important guide. The study suggests the drug is being used in a different profile of patients as that in the rely trial. Dabigatran versus warfarin in patients with atrial fibrillation 1 r. Rely was a noninferiority trial in which 18,1 patients who had atrial fibrillation and a risk of stroke were randomized to receive one of two fixed doses of dabigatran 110 mg or 150 mg twice daily, blinded or adjusteddose warfarin unblinded. The rely trial was published in the new england journal of medicine in 2009. At a median followup of 2 years, highdose dabigatran reduced the. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the chads 2 score. An analysis of the randomized evaluation of longterm anticoagulant therapy rely trial. In questioning the reliability of the rely trial results, tsang and others 1 unfortunately based their concerns on a misinterpretation of the data that were published in the original trial report. Dabigatran for stroke prevention in atrial fibrillation. Pradaxa dabigatran etexilate mesylate capsules for oral use.
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