October 23, 2017

Genetic Testing Helps Determine Safest Dose of Warfarin for Patients Undergoing Hip, Knee Arthroplasty

SALT LAKE CITY, Utah -- October 23, 2017 -- A new 5-year study of nearly 1,600 patients finds that genetic testing can help determine the safest dose of warfarin, with fewer side effects, in patients undergoing joint replacement surgery.

The study, published in JAMA, showed that when physicians dose according to a patient’s genetic makeup when prescribing warfarin, the numbers of adverse side effects like haemorrhage are significantly decreased.

Compared with patients who received a standard dose, patients who received genetically-dosed warfarin had a 27% reduction in complications.

Specifically, their major bleeding was reduced by 75%, the incidence of excessive international normalised ratios was reduced by about 30%, and blood clots occurred 15% less often. No patients died during the study.

The randomised clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty.

“In 2017, what I think GIFT shows us is that when we give warfarin based on an individual’s genes, we can reduce their risk for adverse outcomes compared to using a standardised approach,” said Scott Woller, MD, Intermountain Medical Center, Salt Lake City, Utah. “What's uncertain now is how that observation can be pragmatically adopted clinically to provide cost-effective care.”

Brian F. Gage, MD, Washington University, Seattle, Washington, played a significant role with other researchers in creating an algorithm that uses an individual’s genetics to prescribe a more precise personalised dose of warfarin. The algorithm weighs individual patient characteristics, such as gender, weight, age and race, as well as one’s genetics.

Dr. Woller said it’s important to understand that the dose that will put a patient in the 2-3 international normalised ratio therapeutic range can vary greatly. Some patients require just 0.5 mg of warfarin a day, while others might require 15 to 20 mg a day.

“If we can identify the person who requires 0.5 mg, we’ll start by giving them a low dose and it’s less likely we’ll overshoot,” he said. “Likewise for the patient who requires 20 mg, we'll avoid lower dosing initially. Rather, we'd start by giving them significantly more because we know their stable warfarin dose will be higher.”

“The challenge has always been cost-effectiveness, because you need to do genotyping on an individual and historically that hasn't been cheap,” said Dr. Woller. “The day may come when patients go to the doctor, have their blood pressure taken, and then a cheek swab is used to genotype their whole genome. The information would be available in the future, if they needed warfarin to protect against blood clots or to guide the dosing of antibiotics dependent on genetics for metabolism, for example, or to assess personal risk for breast cancer.”

Reference: DOI: 10.1001/jama.2017.11469

SOURCE: Intermountain Medical Center

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