Hospitalizations Reduced With Warfarin Sensitivity Testing

Hospitalizations are reduced by the upfront use of a genetic test for "warfarin sensitivity," according to new results from a comparative-effectiveness study. The Medco- and Mayo-sponsored trial of the anticoagulant (the dosing of which has caused more than one headache in physicians and patients during the last 70 years) compared hospitalization rates among warfarin-treated subjects who underwent genetic testing and those who didn't. The trial results were presented this morning at the ongoing meeting of the American College of Cardiology in Atlanta; data are also available at the company's web site.

In the study, the dose of newly initiated warfarin therapy in nearly 900 adult patients* was adjusted on the basis of Medco's genetic test (performed on blood or cheek swabs). During a 6-month period, the hospitalization rate in this group was 31% lower than that of a historical control group (N = 2688) who had not undergone genetic testing (ITT analysis: ~18% vs ~25%). The hospitalization rate for bleeding or thromboembolism was 28% lower in the genotyped group.

Results from the per-protocol analysis were even more impressive. The rate of all-cause hospitalization and the rate of hospitalization for bleeding or thromboembolism were 33% and 43% lower, respectively, in the genotyped group.

The genetic test, which is available from several companies,** assesses the function of 2 genes, CYP2DC and VKORC1. The former encodes a well-known P450 enzyme that metabolizes warfarin; the latter encodes an enzyme that activates vitamin K (which counteracts the anticoagulant properties of warfarin). The cost of a warfarin sensitivity test is quoted in the press at a range of $250-$400. The FDA first approved use of the genetic test (Verigene; Nanosphere) to inform warfarin dosing in 2007.

According to Medco, about 30 million warfarin prescriptions are written and 2 million patients start warfarin treatment each year. Warfarin is the leading cause of ED visits, hospitalizations, and drug-related deaths. One third of the variability in response to the drug is ascribed to the genetically determined function of CYP2C9 and VKORC1.

Last week, the FDA added a boxed warning to the PI for the antiplatelet drug clopidogrel (Plavix; BMS/sanofi), which may be less effective in patients with reduced function of the CYP2C19 enzyme. (To become active, clopidogrel, a prodrug, must be converted by CYP2C19.) The FDA advised that 2%-14% of Americans are "poor metabolizers" of clopidogrel. CYP2C19 testing is also commercially available through a number of companies.

ITT = intent to treat; PI = package insert.

* Patients were recruited through 29 Medco-managed prescription benefit plans.

** For example, Ambry Diagnostics and Arup Laboratories.

Image of warfarin (Coumadin) bottles from NIGMS/NIH.