Results of the EmbraceAC Trial: A Head-to-Head Comparison of Warfarin with Tecarfarin, A New Anticoagulant.

Abstract 3135

Poster Board III-72

EmbraceAC was conducted to evaluate whether tecarfarin (T) is superior to optimized warfarin (W) as measured by interpolated time in therapeutic range (TTR). T is a novel vitamin K antagonist free of CYP-based metabolism.

EmbraceAC was a 6-9 month randomized, double-blind, multicenter study of optimized W vs. T using a dose control center (DCC) and prospective genotyping in oral anticoagulation patients. Data from weekly INR monitoring was analyzed on an ITT basis. A total of 612 patients from 47 sites (94.3% warfarin experienced; 74.5% treated for AF, 15.7% for DVT/PE, 14.2% for cardiomyopathy/MI, and 15.5% for heart valve) were randomized (305 to W, 307 to T). Mean interpolated TTR was 73.2% for W and 74.0% for T (p, 0.51). Pre-specified subgroup analyses of warfarin experienced patients, wild-type CYP2C9 patients, and on-treatment analysis all showed statistically significant superiority of T over W. For the 31% of patients taking drugs that inhibit CYP2C9, the observed TTR for W decreased, whereas the TTR for T remained steady. There was no significant difference in the composite of clinical outcomes (death, stroke, MI, DVT, PE, or major hemorrhage): 6 for W and 8 for T (p, 0.41). Tolerability was good with both treatments and there were no differences in overall AE rate. TTR for W was exceptionally high, perhaps as a result of frequent monitoring, availability of accurate and timely genotype information, close surveillance by the DCC and early dose adjustment for potential interacting drugs. Statistical superiority of T was not established in the primary end point. As hypothesized for a drug designed to avoid CYP metabolism, T showed a significant advantage over W for patients exposed to CYP2C9 inhibitors.

DG - Consultant to Bristol Meyers Squibb, CSL Behring, ARYx Therapeutics; PM, DC, DE - ARYx Therapeutics employees.