Most long-term warfarin patients won’t retain stable blood levels

Data from 3,749 patients show that 66% of patients with stable warfarin levels did not maintain stability after 18 months of warfarin treatment.

Blood cells in an artery

Only a third of patients taking warfarin will retain stable blood levels in the long term, a new study published in JAMA
has revealed (online, 9 August 2016).

In a study of 3,749 patients taking the blood thinning drug warfarin, 26% had stable levels in their blood for six months. But only 34% of these maintained stable warfarin levels for another year. In addition, 36% of previously stable patients recorded either a very high or very low level of warfarin in their blood over the subsequent year.

Warfarin is often used to prevent stroke in patients with atrial fibrillation, but it needs to be carefully monitored to ensure that the amount in the blood is both safe and effective. This is done by calculating the international normalised ratio (INR), a standardised measure of the patient’s prothrombin time, a test that shows how fast the blood clots in patients receiving oral anticoagulant medication.

New oral anticoagulants that do not require monitoring and dose adjustment, such as dabigatran, rivaroxaban and apixaban, have become available in the past five to eight years but it has been suggested that stable warfarin patients would not necessarily benefit from switching to one of the new, arguably more convenient, alternatives[2]

The researchers from Duke University in North Carolina say their findings challenge this view. “This analysis suggests warfarin stability is difficult to predict and challenges the notion that patients who have done well taking warfarin should maintain taking warfarin.”

The authors used data collected from the ‘Outcomes registry for better informed treatment of atrial fibrillation’, which includes patients enrolled at 176 different clinics across the United States whose INR was tested at least every other month. The average age of the patients in the study was 75 years old, 43% were women and 91% were white. Patients not taking warfarin or who did not have regular monitoring were excluded. Of the regularly monitored warfarin patients, 37% were also taking aspirin and 5% were also taking clopidogrel.

The researchers classed patients with an INR between 2.0 and 3.0 in more than 80% of tests as having stable warfarin levels.

However, Naomi Ratcliffe, clinical pharmacy manager at Hampshire Hospitals NHS Trust who has a specialist interest in cardiovascular pharmacy, comments: “In clinical practice, slightly wider variation in INR may be appropriate for some patients after considering individual risk of bleeding versus thrombosis.”

She adds that information about the patients’ targeted INR was not recorded in the study, “potentially increasing the [actual] numbers in ‘therapeutic range’”.

Ratcliffe also points out that, in practice, patients are classed as stable when their INR is in the correct range more than 65% of the time, not the 80% mark used in the study.

She concludes that the finding that previous stability does not indicate future stability “reinforces the message that continuous review of warfarin suitability is required alongside continuous INR monitoring”.


[1] Pokorney SD, Simon DN, Thomas L et al. Stability of international normalized ratios in patients taking long-term warfarin therapy. JAMA 2016;316:661-663. doi: 10.1001/jama.2016.9356 

[2] Lip GY, Laroche C, Ioachim PM et al. Prognosis and treatment of atrial fibrillation patients by European cardiologists. Eur Heart J 2014;35:3365-3376. doi: 10.1093/eurheartj/ehu374

Last updated
The Pharmaceutical Journal, Most long-term warfarin patients won’t retain stable blood levels;Online:DOI:10.1211/PJ.2016.20201559

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