Mechanical heart valve recipients: anticoagulation in patients with genetic variations of phenprocoumon metabolism

OBJECTIVES: Oral anticoagulation in mechanical heart valve recipients remains crucial, and vitamin K antagonists (VKA) are still the gold standard. Polymorphisms of vitamin K epoxide oxidase reductase (VKORC) and cytochrome p450 (CYP2C9) were recently found to influence VKA metabolism. We retrospectively investigated the prevalence of these genotypes and associated anticoagulation-related complications in our patients. METHODS: Between August 1998 and August 2008, 563 patients received mechanical heart valve replacement in our institution. Of these, 179 completed a questionnaire on anticoagulation-related complications and consented to genetic analysis. We analysed polymorphisms of VKORC (−1639 G>A; 1173 C>T) and of CYP2C9 (*2, 144 C>T; *3, 359 A>C) by PCR and restriction analysis. RESULTS :F or VKORC −1639/1173 alleles, there were 62 (35%) patients with the combination GG/CC, 91 (51%) with GA/CT, 25 (14%) with AA/TT and 1 (1%) with AA/CT. Phenprocoumon (PC) dosage was related to VKORC polymorphism (P 1.5 was associated with severe bleeding complications (P =0 .025) and GA/CT patients were predisposed to INR variations >1.5 (P =0. 028). No influence of CYP2C9 polymorphism on PC dosage and anticoagulation-related complications was found. CONCLUSIONS: VKORC polymorphism affects PC dosage and anticoagulation-related complication rates in mechanical heart valve recipients. Genotyping may help to identify patients at particular risk of anticoagulation-related complications.