ABSTRACT
BACKGROUND: During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. METHODS AND RESULTS: Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. CONCLUSIONS: During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.
Subject(s)
Antithrombins/administration & dosage , Atrial Fibrillation/drug therapy , Benzimidazoles/administration & dosage , Embolism/prevention & control , Stroke/prevention & control , beta-Alanine/analogs & derivatives , Aged , Aged, 80 and over , Antithrombins/adverse effects , Atrial Fibrillation/mortality , Benzimidazoles/adverse effects , Dabigatran , Dose-Response Relationship, Drug , Embolism/mortality , Female , Follow-Up Studies , Hemorrhage/chemically induced , Hemorrhage/mortality , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Stroke/mortality , Treatment Outcome , beta-Alanine/administration & dosage , beta-Alanine/adverse effectsABSTRACT
OBJECTIVES: To examine the impact of prognostic factors on the outcome of treatment with warfarin or aspirin after acute myocardial infarction. METHODS: Patients from the Warfarin Aspirin Re-Infarction Study, assigned to treatment with warfarin (n = 1,216) or aspirin (n = 1,206) after myocardial infarction, were stratified according to important prognostic factors. Survival from the composite endpoint of death, myocardial infarction and thromboembolic stroke was estimated within each stratum by odds ratios (OR). The effect of therapy was then tested for heterogeneity across the two groups. Unadjusted analyses were complemented with regression analyses. RESULTS: In diabetics the OR was 1.54 (95% CI 0.80-2.94) compared to 0.75 (95% CI 0.60-0.93) in nondiabetic patients. The latter difference was statistically significant when testing for heterogeneity, suggesting effect modification of warfarin by diabetes. After adjusting for confounders, diabetic patients who received warfarin had a 56% excess risk of an endpoint as compared with those receiving aspirin. By contrast, nondiabetic patients on warfarin had a 22% lower risk of an endpoint than those allocated to aspirin. CONCLUSIONS: The present data suggest less benefit from warfarin as compared to aspirin in diabetics. The mechanisms behind this remain in question.
