title: Oral anticoagulation and VKORC1 polymorphism in patients with a mechanical heart prosthesis: a 6-year follow-up.
abstract: Therapy with Vitamin K antagonists (VKA) effectively reduces the thrombosis risk in many clinical conditions. Genetic variants of vitamin K epoxide reductase (VKORC-1) are associated with increased VKA effect and bleeding risk. It is unknown whether these variants could also affect the long-term outcome in patients with high-dosage oral anticoagulation and/or more difficult adherence to the therapeutic INR range. Hundred and twenty-four patients with mechanical heart valve replacement assuming VKA were genotyped for VKORC-1 -1639G>A (Rs9923231) polymorphism. Hemorrhage, venous thrombosis and atherothrombotic events were retrospectively assessed for a 6-year period. Furthermore, stability of their INR in relationship with the VKORC-1 genotype was investigated day-by-day for 3 months. No differences were observed in hemorrhage and venous thrombosis events according to rs 9923231. GG genotype carriers (n = 41) had no atherothrombotic events, while 4 strokes, 4 TIA and 3 AMI were diagnosed in A carriers (n = 83; P = 0.0008). During the daily observation period, A allele carriers had lower VKA requirements (4.7, 3.7, 2.2 mg/day for GG/GA/AA genotype respectively; P = 0.00001), higher mean INR (2.7, 2.8, 2.9; P = 0.05) and a higher number of examinations above the therapeutic range than GG carriers (17 % vs. 0 % in GG genotype, P = 0.036). Conversely, patients with GG genotype had a more stable dosage of VKA (P = 0.006) and a higher percentage of examinations under the therapeutic range (51, 43 and 36 % in GG, GA and AA genotype, respectively, P = 0.040). In patients with high dosage VKA, VKORC-1 polymorphism is associated to a different warfarin dosage, anticoagulation level, time spent outside the therapeutic range and, in the long-term, a different incidence of atherothrombotic events.
authors.affiliation: S.C. Clinica Medica Generale e Terapia Medica, Department of Scienze Mediche, Chirurgiche e della Salute, University of Trieste, Ospedale di Cattinara, Strada di Fiume, 447, 34149, Trieste, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Giansante
authors.forename: Nicola
authors.initials: N
authors.lastname: Fiotti
authors.forename: Nicola
authors.initials: N
authors.lastname: Altamura
authors.forename: Paola
authors.initials: P
authors.lastname: Pitacco
authors.forename: Lara
authors.initials: L
authors.lastname: Consoloni
authors.forename: Sabino
authors.initials: S
authors.lastname: Scardi
authors.forename: Carmine
authors.initials: C
authors.lastname: Mazzone
authors.forename: Gabriele
authors.initials: G
authors.lastname: Grassi
authors.forename: Claudio
authors.initials: C
authors.lastname: Pandullo
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Lenarda
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006350:Heart Valve Prosthesis; D006470:Hemorrhage / Q000209:etiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D020521:Stroke / Q000209:etiology / Q000235:genetics; D013997:Time Factors; D020246:Venous Thrombosis / Q000209:etiology / Q000235:genetics; D014812:Vitamin K / Q000037:antagonists & inhibitors; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases