• Thrombotic Disorders
• Cerebrovascular Disease
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• Cardiology Clinical Trials

Previously, the Randomized Evaluation of Long-Term Anticoagulation Therapy [RE-LY] trial evaluated two doses of dabigatran (110 and 150 mg BID; open dabigatran but blinded dose) versus warfarin (open-label) in patients with nonvalvular atrial fibrillation and at least 1 risk factor for stroke [Flaker et al. J Am Coll Cardiol 2012]. The goal of the RELY-ABLE extension study [NCT00808067] presented by Stuart J. Connolly, MD, McMaster University, Hamilton, Ontario, Canada, was to describe the long-term efficacy and safety of ongoing dabigatran therapy after the RE-LY trial.

Patients who had been randomized to dabigatran and were still taking it at then end of the the blinded dose of dabigatran taken in RE-LY trial were eligible for the was continued in the RELY-ABLE extension study. Patients continued on the same dose of dabigatran (the dose of dabigatran remained blinded) trial for a mean of 2.3 years. In the RE-LY trial, patients were randomized to dabigatran 110 mg (n=6015) or dabigatran 150 mg (n=6076) in a blinded fashion, or open-label warfarin (n=6022). Among these, 4492 (75%) in the 110-mg arm and 4519 (75%) in the 150-mg arm completed RE-LY and were still receiving dabigatran. Of these, 3395 (76%) in the 110-mg arm and 3397 (75%) in the 150-mg arm were beeing followed at a site participating in RELY-ABLE.

A total of 2914 patients receiving dabigatran 110 mg and 2937 patients receiving dabigatran 150 mg were enrolled in RELY-ABLE, and 2511 and 2508 patients, respectively, completed the study, representing 86% and 85% of the patients.

During 2.3 years of additional dabigatran treatment after RE-LY (total mean follow up of 4.3 years), rates of stroke and major bleeding remained low and comparisons of the 2 doses were consistent with those observed during the main RE-LY trial. The rates of stroke and myocardial infarction (MI) from the RELY-ABLE and RELY trials are compared in Table 1.

At a mean follow-up of 2.3 years, the cumulative risk of stroke or systemic embolism was 1.46%/year with 150 mg dabigatran versus 1.60%/year with dabigatran 110 mg (HR, 0.91; 95% CI, 0.69 to 1.20). Other endpoint results at 2.3 years were stroke, 1.24%/year with dabigatran 150 mg versus 1.38%/year with dabigatran 110 mg (HR, 0.89; 95% CI, 0.66 to 1.21); ischemic stroke, 1.15%/year versus 1.24%/year (HR, 0.92; 95% CI, 0.67 to 1.27); hemorrhagic stroke, 0.13%/year versus 0.14%/year (HR, 0.89; 95% CI, 0.34 to 2.30); MI, 0.69%/year versus 0.72%/year (HR, 0.96; 95% CI, 0.63 to 1.45); and pulmonary embolism, 0.13%/year versus 0.11%/year (HR, 1.14; 95% CI, 0.41 to 3.15).

Stroke and systemic embolism results for patients in the RELY-ABLE study who received 150 mg versus 110 mg dabigatran at a mean follow-up of 4.25 years (were 0.89%/year versus 1.05%/year at a mean follow-up of 4.25 years,) and 1.25%/year versus 1.54%/year in all dabigatran patients (RE-LY and RELY-ABLE) at a mean follow-up of 3 years. (1.25%/year vs 1.54%/year).

Patients treated with dabigatran 150 mg had higher rates of major bleeding (3.74%/year) compared with dabigatran 110 mg (2.99%/year) at 2.3 years in the RELY-ABLE extension study. Life-threatening, intracranial, and extracranial bleeding were higher with 150 mg versus 110 mg dabigatran, whereas GI and fatal bleeding were similar in both groups. Total mortality in the RELY-ABLE study at 2.3 years follow up with 150 mg versus 110 mg dabigatran was 3.02%/year and 3.10%/year.

Patients in both dabigatran dose groups had very low rates of hemorrhagic stroke over more than 4 years. Patients who continued in RELY-ABLE treated with 150 mg compared with 110 mg of dabigatran had low ischemic stroke/systemic emboli rates (1.46%/year and 1.60%/year, respectively) but higher major bleeding rates (3.74%/year and 2.99%/year, respectively). These two doses of dabigatran were associated with similar mortality rates. Whether the trade-off between the yearly risk of stroke/embolism protection and major bleeding changes over time, and whether a break-even point exists when that trade-off becomes equivalent or even unfavorable, deserves further study.

• © 2012 MD Conference Express®