The influence of polymorphisms ofVKORC1andCYP2C9on major gastrointestinal bleeding risk in anticoagulated patients
| Autor: | Ramón Montes, José Hermida, José M. Zozaya, Óscar Nantes, Alvaro Alonso |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Risk medicine.medical_specialty Gastrointestinal bleeding medicine.drug_class Amiodarone Lower risk Gastroenterology Drug Administration Schedule Mixed Function Oxygenases Vitamin K Epoxide Reductases Internal medicine Odds Ratio Humans Medicine Genetic Predisposition to Disease International Normalized Ratio CYP2C9 Aged Cytochrome P-450 CYP2C9 Aged 80 and over Acenocoumarol Aspirin Polymorphism Genetic business.industry Anti-Inflammatory Agents Non-Steroidal Anticoagulant Anticoagulants Hematology Odds ratio medicine.disease Vitamin-K-epoxide reductase (warfarin-sensitive) Surgery Case-Control Studies Female Aryl Hydrocarbon Hydroxylases Hydroxymethylglutaryl-CoA Reductase Inhibitors Gastrointestinal Hemorrhage business Anti-Arrhythmia Agents medicine.drug |
| Zdroj: | British Journal of Haematology. 143:727-733 |
| ISSN: | 1365-2141 0007-1048 |
| Popis: | Summary The VKORC1 c.−1639G>A and CYP2C9 c.430C>T and c.1075A>C polymorphisms have been associated with increased sensitivity to oral anticoagulants. However, their role in gastrointestinal bleeding is unknown. We studied the risk of gastrointestinal bleeding associated with these polymorphisms, and how this risk was influenced by the anticoagulant dose and the use of common drugs. Eighty-nine patients with gastrointestinal bleeding during acenocoumarol therapy and 177 patients free of bleeding during acenocoumarol therapy were studied. None of the three polymorphisms constituted a serious gastrointestinal bleeding risk factor. However, patients bearing at least one of these polymorphisms were at high risk, when they simultaneously met one of the following conditions: a weekly dose of acenocoumarol higher than 15 mg [adjusted Odds Ratio (OR) (95% confidence interval (CI) = 4·19 (1·59–11·04)]; amiodarone use [adjusted OR (95% CI) = 9·97 (1·75–56·89)]; or aspirin use [adjusted OR (95% CI) = 8·97 (1·66–48·34)]. The consumption of statins was associated with a lower risk of gastrointestinal bleeding [adjusted OR = 0·50 (0·26–0·99)]. The risk of gastrointestinal bleeding during acenocoumarol therapy in carriers of any of the studied polymorphisms is severely increased with exposure to weekly doses of acenocoumarol higher than 15 mg or the use of amiodarone or aspirin. |
| Databáze: | OpenAIRE |
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