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

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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.

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Acknowledgments

The study has been supported by a Grant to C.G. (Fondo Trieste 2006).

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Authors and Affiliations

  1. 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

    Carlo Giansante, Nicola Fiotti, Nicola Altamura, Paola Pitacco & Lara Consoloni

  2. Centro Cardiologia Sociale, Azienda Sanitaria Territoriale n 1 “Triestina” Via Farneto 3, 34142, Trieste, Italy

    Sabino Scardi, Carmine Mazzone, Claudio Pandullo & Andrea Di Lenarda

  3. Department of Life Sciences, University of Trieste C/O, Department of “Scienze Mediche, Tecnologiche e Traslazionali”, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy

    Gabriele Grassi

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  1. Carlo Giansante
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  2. Nicola Fiotti
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  3. Nicola Altamura
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  4. Paola Pitacco
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Correspondence to Nicola Fiotti.

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11239_2012_740_MOESM1_ESM.doc

Figure 1. Comparison of Bioanalyzer and sequencing results for -1639G>A polymorphism. Msp I digested amplicons were analyzed on Bioanalyzer (A, C, and E) and compared to results of direct sequencing of the reverse strand (B, D, and F). A, B= GG genotype; C, D = GA genotype; E, F = AA genotype. Supplementary material 1 (DOC 107 kb)

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Giansante, C., Fiotti, N., Altamura, N. et al. Oral anticoagulation and VKORC1 polymorphism in patients with a mechanical heart prosthesis: a 6-year follow-up. J Thromb Thrombolysis 34, 506–512 (2012). https://doi.org/10.1007/s11239-012-0740-8

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  • DOI: https://doi.org/10.1007/s11239-012-0740-8

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