19 March 2010
The use of genetic testing to predict how different individuals will respond to particular drugs is one of the major areas where genomics is expected to yield enormous clinical benefits across a range of diseases (see previous news). Understanding how an individual’s response to medication may be affected by their genetic sequence (pharmacogenetics) could improve dosing, reduce adverse drug reactions and allow targeting of drugs.
One of the first drugs where pharmacogenetic information could be useful for judging the best dosage to prescribe to patients is warfarin, the world’s most popular anti-coagulant, which in addition to preventing blood clots may also cause serious bleeding events in a large number of patients. Common variants in just two genes (CYP2C9 and VKORC1) explain most of the variation in drug response, so it has been suggested that genetic testing could be used to determine whether an individual is a slow or fast metaboliser and hence help physicians decide what dosage to prescribe . However, to date, although there is good evidence for the clinical validity for this test, evidence of improved clinical outcomes as a result of testing has been lacking (see previous news).
The results of a trial designed to test whether genotyping reduced the chance of warfarin patients being hospitalised were announced this week at the American College of Cardiology annual Meeting. The hospitalisation rates of nearly 900 new warfarin patients with genotyping results were compared with rates for a historical control group of similar patients without genotyping. The results suggest that genotyping warfarin patients resulted in a 30% reduction in hospitalisations. Dr Robert Epstein of the Medco Research Institute in New Jersey, said, "Our study shows that genetic testing is a tool clinicians can use to more accurately predict the best warfarin dose early on. Patients may get to a stable dose more quickly and therefore have a lower risk of negative outcomes" (reported in The Heart).
Comment: This study provides strong evidence of clinical utility for using genetic testing to determine the best dosage of warfarin. If it also proves to be cost-effective versus using traditional clinical methods for adjusting warfarin dosage, the UK NHS may have to follow the US FDA’s lead in recommending (see previous news) and ultimately implementing genotyping for new warfarin patients.