Oral anticoagulation and VKORC1 polymorphism in patients with a mechanical heart prosthesis: a 6-year follow-up

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• 作者：Carlo Giansante (1)
  Nicola Fiotti (1) fiotti@units.it
  Nicola Altamura (1)
  Paola Pitacco (1)
  Lara Consoloni (1)
  Sabino Scardi (2)
  Carmine Mazzone (2)
  Gabriele Grassi (3)
  Claudio Pandullo (2)
  Andrea Di Lenarda (2)
• 关键词：Oral anticoagulation – ; VKORC1 – ; Polymorphisms – ; Mechanical heart valve prosthesis
• 刊名：Journal of Thrombosis and Thrombolysis
• 出版年：2012
• 出版时间：November 2012
• 年：2012
• 卷：34
• 期：4
• 页码：506-512
• 全文大小：203.4 KB
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• 作者单位：1. S.C. Clinica Medica Generale e Terapia Medica, Department of 鈥淪cienze Mediche, Chirurgiche e della Salute鈥? University of Trieste, Ospedale di Cattinara, Strada di Fiume, 447, 34149 Trieste, Italy2. Centro Cardiologia Sociale, Azienda Sanitaria Territoriale n 1 鈥淭riestina鈥?Via Farneto 3, 34142 Trieste, Italy3. Department of Life Sciences, University of Trieste C/O, Department of 鈥淪cienze Mediche, Tecnologiche e Traslazionali鈥? University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy
• ISSN：1573-742X

文摘

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.