A study by pharmacy benefits management company Prime Therapeutics is being touted as evidence that genetic testing for warfarin is being misapplied. A press release on the study noted that physicians prescribe CYP2C9 analysis for only 4% of warfarin patients and that:
…despite its rare use, nearly two-thirds of those patients on warfarin who received a genetic test were tested inappropriately, typically those who have already been on the drug for five days or more.
The authors of the study draw the 5-day appropriate/inappropriate line based on criteria published by CMS for Medicare beneficiaries. However, the CMS standard is not a universal definition of appropriateness.
Evidence shows that pharmacogenetic testing for warfarin is relevant beyond initial dosing. In fact, it is well documented and understood that the genetic factors that influence warfarin response do so by altering the metabolic clearance of warfarin and by altering the concentration of warfarin in the blood needed for the therapeutic response. The relationships between drug clearance and target therapeutic concentration to all forms of dosing — including not just loading dosages, but also maintenance and transitional dosing — are fundamental, and may be improved by understanding of the patient’s genetics.
It is likewise a fundamental tenant of clinical pharmacology that alterations in drug clearance influenced by genetic factors dictate when response monitoring (measurement of the INR, in the case of warfarin) and interpretation of response criteria are most reliable.
So the drawing of a simple line — within 5 days of first treatment — may be important for CMS and their goals of the evidence gathering process, but the relevance of testing CYP2C9/VKOR C1 for warfarin stretches far beyond initial dosing.