Couma-Gen: Implications for future randomized trials of pharmacogenetic-based warfarin therapy

Lawrence J. Lesko, Brian F. Gage

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Warfarin is an effective oral anticoagulant used to treat or prevent thromboembolic disorders in millions.of patients worldwide. Even with conscientious International Normalized Ratio (INR) monitoring, warfarin initiation carries a high risk of hemorrhage. Pharmacogenetic studies have determined that variants in the CYP2C9 and VKORC1 genes help to predict the therapeutic warfarin dose. Whether using this information prospectively will,prevent under- and over-dosing of warfarin is unknown. To answer this question, the CoumaGen investigators randomized half of a 200-patient cohort beginning warfarin therapy to clinical dosing and half to pharmacogenetic dosing. Overall, pharmacogenetic dosing slightly increased time in the therapeutic INR range (p = not significant) and decreased the number of INR tests required. The trial has important implications for the new NIH-funded multicentered trial. Here, we discuss the Couma-Gen study and its implications for the design, randomization, blinding and end point definition of future studies.

Original languageEnglish
Pages (from-to)163-168
Number of pages6
JournalPersonalized Medicine
Issue number2
StatePublished - Mar 1 2008


  • Adverse event
  • Algorithm
  • CYP2C9
  • Hemorrhage
  • Pharmacogenetics
  • Study design
  • Treatment outcome
  • VKORC1
  • Warfarin

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