Could Pharmacogenetic Dosing Reduce Warfarin-Related Adverse Events?

Personalizing doses of warfarin through genetic testing helped reduce the risk of combined adverse events in patients undergoing elective orthopedic surgery, according to data presented at the American College of Cardiology's 66th Annual Scientific Session.

The study, named the Genetic InFormatics Trial (GIFT) of Warfarin Therapy, aimed to quantify the benefit of pharmacogenetics dosing of warfarin on clinical events based on the premise that variants in certain genes can influence warfarin sensitivity and metabolism in patients. In the trial, genotype-guided dosing resulted in a 27% reduction in the primary endpoint — which included death, confirmed venous thromboembolism, warfarin overdose, and major bleeding.

Pharmacogenetic dosing also significantly improved INR control, which was the study’s secondary endpoint. The researchers noted that previous trials had provided mixed results in this area, but the GIFT trial was considerably larger, added another gene (CYP4F2), and recruited older patients at high risk of bleeding.

The trial included 1597 participants aged 65 years or older undergoing elective knee or hip replacement surgery. Due to the high risk of bleeding and clotting in these patients, the researchers were able to determine the effects of genotype-guided dosing on post-operative adverse events. Participants were genotyped for genetic variants that influence warfarin sensitivity, warfarin metabolism, and vitamin K recycling.

The group who underwent recommended clinical dosing of warfarin had a 14.7% rate of adverse events compared to 10.8% in the genotype-guided group. INR values ≥ 4 were reduced from 9.6% to 6.9%. However, there were no significant reductions in deep vein thrombosis, pulmonary embolism, or major bleeds.

The researchers concluded that the results could have broader implications for patients being treated with warfarin. Genetic and clinical dosing algorithms could be potentially beneficial in managing warfarin doses and preventing adverse events associated with the treatment, especially if dosing recommendations become readily accessible to providers in electronic medical records.

Reference

Genetically Guided Warfarin Dosing Lowers Risk of Some Adverse Events [news release]. ACC’s website. http://www.acc.org/about-acc/press-releases/2017/03/18/08/47/sun-1045am-genetically-guided-warfarin-dosing-lowers-risk-of-some-adverse-events?w_nav=S. Accessed Mar. 20, 2017.