Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran.
Vitamin K antagonists (VKAs) are effective for stroke prevention in patients with atrial fibrillation (AF) but are difficult to use. Dabigatran etexilate is a prodrug that is rapidly converted to the active direct thrombin inhibitor dabigatran. It is administered in a fixed dose without laboratory monitoring and is being compared with warfarin (international normalized ratio 2-3) in the RE-LY trial. Two doses of dabigatran (110 and 150 mg BID) are being evaluated. RE-LY is a phase 3, prospective, randomized, open-label multinational (44 countries) trial of patients with nonvalvular AF and at least 1 risk factor for stroke. Recruitment concluded with a total of 18,113 patients. Patients who were VKA-naive and experienced are included in balanced proportions. The primary outcome is stroke (including hemorrhagic) or systemic embolism. Safety outcomes are bleeding, liver function abnormalities, and other adverse events. Adjudication of end points is blinded to drug assignment. The trial is expected to accrue a minimum of 450 events with a minimum 1-year of follow-up. RE-LY is the largest AF stroke prevention trial yet undertaken. It is unique because it includes equal numbers of VKA-experienced and naive patients and evaluates 2 different dosages of dabigatran, which may allow tailoring of dosing to individual patient needs. The worldwide site distribution and broad range of stroke risk further increase the general applicability of the trial. Results are expected in 2009.
Lankenau Institute for Medical Research and The Heart Center, Wynnewood, PA, USA. Ezekowitzm@mlhs.org
Michael D
MD
Ezekowitz
Stuart
S
Connolly
Amit
A
Parekh
Paul A
PA
Reilly
Jeanne
J
Varrone
Susan
S
Wang
Jonas
J
Oldgren
Ellison
E
Themeles
Lars
L
Wallentin
Salim
S
Yusuf
D000284:Administration, Oral; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000628:therapy; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017548:Echocardiography, Transesophageal; D004554:Electric Countershock / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D020767:Intracranial Thrombosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012107:Research Design; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D001562:Benzimidazoles; D011725:Pyridines; D014859:Warfarin; D000069604:Dabigatran