Weekly Dose: Warfarin, the blood-thinner that's still used as a rat killer

Warfarin is a blood thinner that has been used for more than 60 years to prevent the formation of clots and strokes. It is most commonly prescribed for people with atrial fibrillation, deep vein thrombosis, pulmonary embolism and prosthetic heart valves.

Atrial fibrillation – an abnormal heart beat or arrhythmia – affects around 1-2% of the population and is a strong independent risk factor for stroke, a condition where a blood clot blocks the flow of blood to the brain.

Warfarin is an effective therapy as it can reduce the annual risk of stroke by two-thirds, from 4.2% to 1.4%. Patients prescribed warfarin for atrial fibrillation will most likely be on the medication for the rest of their lives.

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History

Warfarin is derived from coumarin, a sweet-smelling anticoagulant (blood-clotting) chemical found naturally in sweet clover and many other plants.

Sweet clover plant. Anita Gould/Flickr, CC BY-NC

In 1954, warfarin was approved for clinical use and has remained a popular anticoagulant ever since. Today warfarin is one of the most widely prescribed oral anticoagulant drugs with around 1-2% of adults in the developed world prescribed the medication.

Prior to its clinical application in the early 1950s, warfarin was used as a pesticide to kill rats and mice. It is still used for this purpose today.

Despite its evolution, patients are all too aware of and concerned about warfarin’s origins.

How it’s used

In Australia, warfarin is only available in two commercial preparations: Coumadin® and Marevan®.

These are not interchangeable, as the tablets are provided in different strengths and colours. Doctors recommend patients use the same brand of warfarin to reduce any confusion that could occur due the different coloured tablets and their respective doses.

Warfarin is administered once daily and must be taken at around the same time each day in order to eliminate fluctuations of drug concentration in the body.

The dose of warfarin differs with each patient, as their characteristics vary. While some patients require no more than 0.5mg of warfarin per day, others may need 30mg or more per day for effective anticoagulation. The average dose is 4.5mg a day.

Serious problems can occur when blood is too thin or too thick. To prevent this, doctors routinely monitor patients on warfarin via frequent blood tests (at least monthly) and adjust their dose according to the action required.

How much it costs

Warfarin is covered by the Pharmaceutical Benefits Schedule, which means the government subsidises the cost. Consumers pay A$9-12 (or around A$5.20 for concession card holders). In 2001, the cost of subsidising warfarin totalled A$8.3 million. It is now likely to now be much higher.

The blood tests to monitor the use of warfarin (called the International Normalised Ratio or INR) cost the government A$22.52 each, which amounts to more than A$100 million a year.

The dose of warfarin differs with each patient, as their characteristics vary. Richard Brunton/Flickr, CC BY-NC-ND

How it works

Blood clots are formed in the body through a complex process that uses substances called clotting factors. In order to make these clotting factors, the body needs vitamin K, which you can get from many foods including leafy green vegetables.

Warfarin reduces your body’s ability to use vitamin K to make these clotting factors. This results in Vitamin K and warfarin working against each other. Vitamin K is therefore a good, easy antidote for patients whose blood is too thin.

Balancing the benefits versus harms

Warfarin is renowned for its rate of complications and is a common cause of illness and death. Studies based on medical record reviews show that around 11% of drug complications in hospitalised patients result from anticoagulant therapy. Errors due to anticoagulants are more likely to cause permanent disability (32%) than other mistakes.

Warfarin’s main side effect is that it increases the risk of bleeding events, especially among those aged over 65. As a result, you may bruise more readily or experience nosebleeds. It also means that if you cut or injure yourself, you may bleed more than usual.

The rate of minor bleeding among patients with atrial fibrillation is as high as 16% per year.

More serious bleeding events such as a hemorrhagic stroke, where a blood vessel bursts or weakens and bleeds into the brain, are life-threatening. The annual risk of major bleeding (in the brain or bleeding requiring transfusion or hospitalisation) has ranged between 1.2 to 7.0 episodes per 100 patients.

Identifying factors for bleeding risk is key to preventing complications with warfarin. This includes demographic characteristics but also clinical factors such as being aware of warfarin’s interaction with other medications you are taking, particularly antibiotics.

Behavioural and lifestyle factors can also play a role, as you need to monitor your diet for vitamin K and alcohol intake. Psychological and social factors, such as low mood and poor warfarin education – together with how your warfarin is monitored, managed and administered – can increase your risk.

This makes warfarin a very complex medication. On one hand, warfarin usage in Australia has been steadily increasing at a rate of 9% per year due to its effectiveness in preventing a stroke.

On the other, these known risk factors can influence warfarin stability and have resulted in under-use of warfarin in those most at risk of stroke, the elderly.

Warfarin alternatives

In recent years a number of novel oral anticoagulants (NOACs) have been developed – dabigatran, rivaroxaban and apixaban – which promise to be as or more effective in preventing strokes while also being safer and easier to administer because they don’t require regular blood tests.

But these anticoagulants come with their own challenges. There is no quick and easy antidote and there are concerns about their management and effectiveness within a complex and ageing population in long-term therapy.

In the light of this choice, doctors will need to select the appropriate blood-thinning therapy not only based on the individual drug but, more importantly, on the patient’s suitability and the services and supports available to the patient after treatment is initiated.