Vitamin K Antagonists and Atrial Fibrillation: Time in Therapeutic Range

Researchers evaluated more than 2 decades of evidence on atrial fibrillation patients taking vitamin K antagonists.

When heart rate or rhythm problems lead to atrial fibrillation (AF), medication, medical procedures, and lifestyle changes are 3 lifesaving interventions. Since AF causes blood to pool in the heart's atria (increasing the chances that a blood clot will form, travel to the brain, and cause a stroke), anticoagulation is critical. Globally, the selection of anticoagulants has expanded to allow some choice, but many patients continue to use the older vitamin K antagonists (VKAs). Sometimes, they are accustomed to VKAs and remain on them out of habit. Other times, cost is an issue; although the international normalized ratio (INR)-monitoring required with VKAs is costly, many patients are more concerned with the expense of the insurance copayment for medication. And, a select subgroup of patients—those with metal prosthetic valves—must remain on warfarin. VKA anticoagulation prevents thromboembolic events, but increases hemorrhage risk.

In an article in the July 2014 issue of Thrombosis Journal, researchers from the University of Connecticut examined 23 years of medical research surrounding VKAs (warfarin, the sole option in the United States; acenocoumarol; tecarfarin; phenprocoumon; and fenprocoumon). Their goal was to determine patients’ time spent in therapeutic range (TTR), proportion of INR measurements in range (PINRR), adverse events in relation to INR, and predictors of INR control in AF patients using VKAs.

VKA-treated patients’ INRs were in therapeutic range 61% of the time, and PINRR assessments were within range a mere 56% of the time. During periods patients were outside the therapeutic range, they were more likely to be below range. Thus, thrombosis risk increased. Patients at greatest risk were those treated as community-based outpatients. Patients treated through anticoagulation clinics or in trial settings were better controlled and spent less time outside of the therapeutic range.

VKA-naïve patients who were new to treatment were at greater risk of poor control than patients with longer histories of anticoagulation with VKAs.

All patients experienced thromboembolic and hemorrhagic events, even if their levels were within normal limits. Patients whose INR fell below 2, however, experienced more than half of all thromboembolic events. More than 40% of all hemorrhagic events happened at an INR >3.

North American patients spent significantly less time in the therapeutic range than European or British patients. The authors attribute this to North America’s reliance on warfarin; other VKAs available in Europe have been shown to offer improved TTR.

The authors conclude that VKAs’ efficacy and safety are closely related to the level of INR control achieved, and VKA-treated AF patients often have INRs outside the therapeutic range.