A study from the International Warfarin Pharmacogenetics Consortium (IWPC) confirms that using a patient’s genetic information can make it easier to get the warfarin dose right.
“If the warfarin dose is too high, patients are at risk of hemorrhage, and if it’s too low, they risk blood clots that can lead to stroke, heart attack or even death,” says Brian F Gage, associate professor of medicine at the Washington University School of Medicine in St Louis, USA, and director of the outpatient Anticoagulation Service at Barnes-Jewish Hospital. “Unfortunately, getting the warfarin dose right is like walking a tightrope – it’s very easy to give too little or too much.”
Recently, Gage, Charles Eby, associate professor of pathology and immunology, and colleagues at the School of Medicine developed improved dosing formulas. They calculate the warfarin dose by taking into account the effect of two genes involved in warfarin sensitivity and metabolism. Their research demonstrated that gene-based dosing could more quickly and accurately estimate the appropriate dose of warfarin.
The current study, published in the February 19, 2009, issue of the New England Journal of Medicine, gave gene-based dosing a rigorous test in an international collaboration that included more than 5,000 patients. The patients had been prescribed warfarin in the past and had achieved a stable effective dose.
For the study, the researchers calculated a warfarin dose for each of these patients with the gene-based dosing algorithm and with a formula based only on clinical data. Both formulas incorporate data such as age, body size, medications and race to estimate appropriate warfarin dose, but only the gene-based formula includes genetic information.
Using both formulas, the IWPC researchers checked how closely the calculated dose matched the dose actually used for each patient. In 60% of the patients, the gene-based formula got closer to the actual dose than did the clinical formula.
Almost half of the patients studied had either low or high warfarin dose requirements. Patients in these categories would be at high risk if given the wrong dose. The researchers showed that the gene-based formula was better than the clinical formula at identifying the patients at the low and high ends of the dosing spectrum. It provided significantly fewer overestimations in the low-dose group and significantly fewer underestimations in the high-dose group.
“This research study has made an important advance toward personalising medicine – it uses data from countries around the world to develop a gene-based strategy for warfarin dosing that could benefit a wide range of patients,” said Dr Jeremy M Berg, director of the National Institute of General Medical Sciences, which partially funded the study.