10:43pm Sunday 31 May 2020

Better dosage of common drug after genetic testing

Warfarin is the main anticoagulant taken orally in Sweden and many other parts of the world. In Sweden almost 2 percent of the population is treated. Warfarin is used to reduce the risk of complications in patients with atrial fibrillation and to treat deep vein thrombosis, and lung and heart problems caused by blood clots. Warfarin is extremely useful but difficult to prescribe in the most efficient way.  The treatment needs to be monitored frequently, especially when it is initiated.
–       In international comparison, warfarin dosing is handled well in Sweden, but our study shows that it can be improved further. With the help of rapid genotype testing we can give the patient a tailored dose from the start, says Mia Wadelius, chief physician and lecturer in clinical pharmacology at Uppsala University and lead author.

In a recently completed randomised clinical trial funded by EU FP7, the effect of a tailored initiation of warfarin was compared with standard dosing. Half of the 455 patients were prescribed warfarin based on their genotype test results, age and body size, while the other half were prescribed standard doses. Further dosing was adapted to the patient’s treatment response according to established routines.

Blood clotting was measured using the prothrombin time International Normalised Ratio (INR) and the researchers were looking for the amount of time patients spent within therapeutic INR range during the first three months of treatment. The study showed that patients who received genotype based doses spent more time in the ideal INR range and achieved stable anticoagulation more quickly.

– We have previously shown that it is possible to predict what dose a patient needs with the aid of clinical and genetic factors, says Niclas Eriksson, biostatistician at the Uppsala Clinical Research Center – UCR.  We have now shown in a clinical trial that genetic testing leads to greater precision in the treatment.

– The possible advantages of genetically tailored dosing have been debated, and progress has been slow, says Mia Wadelius. We have now been able to show that personalising warfarin treatment to the patient, based on their genes, age and body size, can help set the right dose when compared with standard treatment. This could have implications for the use of a drug that is taken by millions of people with serious conditions every year.

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