ORLANDO — Patients with atrial fibrillation who are treated with warfarin must be in their target anticoagulation range at least 50% of the time to get a net benefit from treatment.
The longer a patient stays in the target anticoagulation range the better, but when target anticoagulation is reached less than half the time, a patient gets no net benefit from treatment and actually fares worse than getting no treatment at all, Dr. Alan S. Go said at the annual scientific sessions of the American Heart Association.
The standard, target anticoagulant range for patients with atrial fibrillation treated with warfarin is an international normalized ratio (INR) of 2.0–3.0. The results from Dr. Go's analysis confirmed this range yields the best outcomes. Additional results showed the range to be ideal for all patients, even those at age 80 years or older.
A warfarin regimen that keeps a patient in the INR target range less than half the time may harm patients by causing an excess of thromboembolic events or intracranial hemorrhages, said Dr. Go, assistant director for clinical research at Kaiser Permanente of Northern California in Oakland.
If patients on warfarin have trouble staying at an INR of 2.0–3.0, the problem may be caused by diet, alcohol use, use of other medications that interact with warfarin, or noncompliance, he said in an interview. If a patient can't stay in the target range most of the time, one might need to reconsider whether the patient should remain on the drug because it may be causing more harm than good.
Keeping patients in their target anticoagulation range more than half the time seems to depend on managing patients in an anticoagulation service. Kaiser Permanente of Northern California operates 21 anticoagulation clinics even though the service loses money, at least in terms of its direct costs.
In the 13,559 patients with atrial fibrillation who were on warfarin in Kaiser during July 1996-September 2003, 58% were kept at their target INR range 60% or more of the time; 75% were kept in their target range at least 50% of the time. During a median follow-up of 6 years, the entire group of atrial fibrillation patients on warfarin had 1,041 thromboembolic events and 279 intracranial hemorrhages.
When the target INR was reached 50% of the time or less, patients had an excess incidence of thromboembolic events and intracranial hemorrhages. When it was maintained 50% of the time, the rate was neutral, and in patients who maintained the target INR more than half the time, there was a direct relationship between the time spent in the target range and a reduced rate of adverse events. Patients maintained at their target INR at least 70% of the time had the lowest rate of adverse events.
Additional analyses showed that all of the Kaiser atrial fibrillation patients were kept in their target INR range for an average of about 65% of the time regardless of their age, including patients younger than 60 years, and patients age 80 years or older. And keeping patients at an INR of 2.0–3.0 led to lower rates of thromboembolic events and intracranial hemorrhages, regardless of age. In fact, because the rate of adverse events in patients who were not treated with warfarin was highest in patients aged 80 years or older, the net clinical benefit from warfarin treatment maintained in the optimal INR range was greatest in patients aged 80 or older, Dr. Go said.