RELY.ppt-ClinicalTrialResults.ppt

Randomized Evaluation of Long-term anticoagulant therapY Dabigatran Compared to Warfarin in 18,113 Patients with Atrial Fibrillation at Risk of Stroke Sponsored by Boehringer-Ingelheim Atrial Fibrillation and Stroke AF responsible for 1/6 of all strokes Warfarin reduces stroke in AF by 64% significant increase in intracranial and other hemorrhage Difficult to use Only 50% of eligible patients receive warfarin An alternative treatment is needed Dabigatran Dabigatran Etexilate, a pro-drug, is rapidly converted to dabigatran 6.5% bioavailability, 80% excreted by kidney Half-life of 12-17 hours Phase 2 data identified 110 mg BID and 150 mg BID as viable doses RE-LY: A Non-inferiority Trial Atrial fibrillation ≥1 Risk Factor Absence of contra-indications 951 centers in 44 countries R Warfarin adjusted (INR 2.0-3.0) N=6000 Dabigatran Etexilate 110 mg BID N=6000 Dabigatran Etexilate 150 mg BID N=6000 Blinded Event Adjudication. Open Blinded Trial Execution Performed December 2005-March 2009 Median Follow up 2.0 years Follow up 99.9% complete Mean TTR = 64% (patients on warfarin) Baseline Characteristics Characteristic Dabigatran 110 mg Dabigatran 150 mg Warfarin Randomized 6015 6076 6022 Mean age (years) 71.4 71.5 71.6 Male (%) 64.3 63.2 63.3 CHADS2 score (mean) 0-1 (%) 2 (%) 3+ (%) 2.1 32.6 34.7 32.7 2.2 32.2 35.2 32.6 2.1 30.9 37.0 32.1 Prior stroke/TIA (%) 19.9 20.3 19.8 Prior MI (%) 16.8 16.9 16.1 CHF (%) 32.2 31.8 31.9 Baseline ASA (%) 40.0 38.7 40.6 Warfarin Na?ve (%) 49.9 49.8 51.4 Stroke or Systemic Embolism 0.50 0.75 1.00 1.25 1.50 Dabigatran 110 vs. Warfarin Dabigatran 150 vs. Warfarin Non-inferiority p-value 0.001 0.001 Superiority p-value 0.34 0.001 Margin = 1.46 HR (95% CI) Warfarin better Dabigatran better 10 Outcome: Superiority Analysis D 110mg D 150mg warfarin D 110mg vs. Warfarin D 150mg vs. Warfarin Annual rate Annual rate Annual rate RR 95% CI P* RR 95% CI P Stroke or systemic Embolism 1.5 % 1.1 % 1.7 % 0.