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: Carlo Giansante, Nicola Fiotti, Nicola Altamura, Paola Pitacco, Lara Consoloni, Sabino Scardi, Carmine Mazzone, Gabriele Grassi, Claudio Pandullo, Andrea Di Lenarda
• Journal: Journal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 34 Issue 4 Pg. 506-12 (Nov 2012) ISSN: 1573-742X [Electronic] Netherlands
• PMID: 22592842 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Vitamin K
• Warfarin
• Mixed Function Oxygenases
• VKORC1 protein, human
• Vitamin K Epoxide Reductases

Topics

• Administration, Oral
• Aged
• Anticoagulants (administration & dosage)
• Female
• Follow-Up Studies
• Heart Valve Prosthesis
• Hemorrhage (etiology, genetics)
• Humans
• Male
• Middle Aged
• Mixed Function Oxygenases (genetics)
• Myocardial Infarction (etiology, genetics)
• Polymorphism, Genetic
• Retrospective Studies
• Stroke (etiology, genetics)
• Time Factors
• Venous Thrombosis (etiology, genetics)
• Vitamin K (antagonists & inhibitors)
• Vitamin K Epoxide Reductases
• Warfarin (administration & dosage)