Prospective evaluation of a pharmacogenetics-guided warfarin loading and maintenance dose regimen for initiation of therapy.
Blood. 2011 Jul 1;
Authors: Gong IY, Tirona RG, Schwarz UI, Crown N, Dresser GK, Larue S, Langlois N, Lazo-Langner A, Zou G, Roden DM, Stein CM, Rodger M, Carrier M, Forgie M, Wells PS, Kim RB
Single nucleotide polymorphisms in genes affecting warfarin metabolism (cytochrome-P450 2C9, CYP2C9) and response (vitamin-K epoxide reductase complex 1, VKORC1) have an important influence on warfarin therapy, particularly during initiation. However, there is a lack of consensus regarding the optimal pharmacogenetics-based initiation strategy. We conducted a prospective cohort study in which patients requiring warfarin therapy for atrial-fibrillation (AF) or venous thromboembolism (VTE) were initiated using a novel pharmacogenetics-initiation protocol (WRAPID), incorporating loading and maintenance doses based on genetics, clinical variables and response (n=167, followed for 90 days), to assess the influence of genetic variations on anticoagulation responses. Application of the WRAPID algorithm resulted in negligible influence of genetic variation in VKORC1 or CYP2C9 on time to first therapeutic INR (2 - 3; P=0.52, P=0.28) and risk of over-anticoagulation (INR?4; P=0.64, P=0.96). Following adjustment of covariates, time to stable anticoagulation was not influenced by VKORC1 or CYP2C9 genotype. Importantly, time spent within or above range did not differ among VKORC1 and CYP2C9 genotype groups. Moreover, the overall time-course of anticoagulation response among the genotype groups was similar and predictable. We demonstrate the clinical utility of genetics-guided warfarin initiation with the WRAPID protocol for providing safe and optimal anticoagulation therapy for AF and VTE patients.
PMID: 21725053 [PubMed - as supplied by publisher]