Pharmacology Update: New Study Shows Warfarin Remains Underused

In a new study, entitled "Epidemiology and Outcomes in Patients with Atrial Fibrillation in the USA," warfarin was found to be significantly underused in patients with atrial fibrillation. The study, led by Drs. Alexander Walker and Dimitri Bennett, was published in the October 2008 edition of HeartRhythm.¹ In this interview, we speak with Drs. Walker and Bennett about the study findings.

Tell us a little about warfarin therapy. What are the benefits of warfarin for atrial fibrillation (AF) patients?

Patients with atrial fibrillation often form thrombi, or blot clots, in the atrium, which is not beating effectively. These clots can break off to form emboli, causing stroke. Warfarin inhibits the clotting process, and therefore, reduces the risk of thromboembolism including stroke.

What were your reasons for doing this study analysis? Describe the study design.

The primary goal was to document how extensively and how well warfarin was being used in patients with AF. The study design included retrospective claims and lab database analysis from the Ingenix Research Data Mart between January 1, 1999 to June 30, 2005.

It's very interesting that 48% of patients had no claim to receive any anticoagulant or antiplatelet therapy. How do you explain this high percentage?

Not all patients with AF are thought to be at high risk of stroke. More importantly, warfarin is a very difficult drug to manage, so doctors often decide not to prescribe it.

Why might doctors under-prescribe or underdose warfarin? What are some of the complications or practical difficulties associated with warfarin use?

The effective dose of warfarin can change erratically in a person as a result of secondary effects of other drugs or dietary factors. Doctors may want to keep the dose relatively low so that there is less danger of a swing to over-thinning of the blood. Patient-related factors include increasing age, embolic risk, or risk for bleeding episodes.

Tell us about your analysis.

The data came from insurance and laboratory records available to UnitedHealthcare for 117,000 patients with insurance claims for atrial fibrillation and flutter. All patients were over the age of 40. Our analysis provided descriptive statistics and incidence rates of various outcomes. In addition, the risk of stroke was estimated using Poisson regression modeling.

Which patients were most likely to be prescribed warfarin or anticoagulants?

Men and patients with a history of stroke, hypertension and diabetes were more likely to receive warfarin. Patients under the age of 60 were less likely.

What comparisons were made between male and female patients in this study?

We did not examine the question of an effect of gender on tolerance of warfarin. Among treated persons, and after accounting for INR and other factors, men were at less risk for stroke than were women.

Only 19% of patients spent their time within the therapeutic INR range. Explain the risks associated with subtherapeutic and supratherapeutic INR. Do the risks associated with INR outside the therapeutic range outweigh the benefits of warfarin? How might INR be better managed?

If patients did not receive warfarin, they would uniformly have the high risks associated with subtherapeutic doses. Even at the suboptimal levels of treatment that we observed, treatment is much better than nontreatment. Management of INR requires dedicated resources, but even so is unlikely ever to achieve a state where all patients spend the great majority of their time within therapeutic range. Eventually there will be oral anticoagulants whose performance is superior to warfarin.

Why are these study findings significant?

These findings provide confirmation that difficulties in managing warfarin, which have been noted before, are still a very important part of the contemporary U.S. medicine.

For more information, please visit: www.hrsonline.org