Dabigatran superior to warfarin irrespective of INR control
MedWire News: Patients with atrial fibrillation (AF) have fewer strokes and bleeding events when taking dabigatran than when treated with warfarin, even if their international normalized ratios (INRs) are strictly controlled, shows further analysis of the RE-LY study.
The RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) study, which included 18,113 AF patients, originally found that twice-daily dabigatran 150 mg prevented more strokes than did warfarin and had a similar safety profile, whereas the 110 mg dose was noninferior in terms of stroke prevention but had a better safety profile.
However, control of INR varied widely among the 951 study centers, with the average time their patients spent within the therapeutic range of 2.0-3.0 (TTR) ranging from 44% to 77%.
Higher individual TTRs were associated with lower rates of stroke and systemic embolism, major bleeding, and total mortality. The major independent predictor of individual TTRs was the average TTR for the relevant study center.
Overall, the finding of superior stroke and embolism prevention with dabigatran 150 mg and noninferior prevention with the 110-mg dose versus warfarin remained consistent after accounting for centers' average TTR, Lars Wallentin (Uppsala University, Sweden) and team report in The Lancet.
TTR also did not interact with the relationship of intracranial bleeding with dabigatran versus warfarin.
But TTR did influence the relationship of major bleeding with treatment allocation, with event rates similar for patients given dabigatran 150 mg and those given warfarin by a center that maintained a high average TTR, but higher among warfarin-treated patients from centers with poor TTR maintenance (bottom quartile; TTR <57·1%).
Major bleeding rates were lower with dabigatran 110 mg than warfarin regardless of TTR.
"These findings support the lower bleeding risk of 110 mg dabigatran compared with warfarin irrespective of the centers' quality of INR control and a lower bleeding risk of the higher dabigatran dose at sites with poor INR control," say Wallentin et al.
They add that the results "show that local standards of care affect the benefits of use of new treatment alternatives."
In a commentary accompanying the research paper Deirdre Lane and Gregory Lip (University of Birmingham, UK) said the analysis shows that "dabigatran is not simply superior or noninferior to warfarin because of poor INR control."
They said that the findings reinforce the importance of good INR control for preventing adverse embolic and bleeding events, but noted that "either dose of dabigatran was associated with fewer adverse events than was warfarin."
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By Eleanor McDermid