Optimal candidates for a switch from vitamin K antagonists (VKAs) like warfarin to direct oral anticoagulants (DOACs) have long been identified by a single statistic—time-in-therapeutic range (TTR)—but a recent Danish analysis of anticoagulants in atrial fibrillation patients suggests the marker might be less insightful than previously thought.
The study, published in the September issue of the Journal of the American College of Cardiology and led by first author Anders Nissen Bonde, of Copenhagen University Hospital Herlev and Gentofte in Hellerup, Denmark, sought to evaluate the stability of TTR in a nearly 5,000-strong population of AFib patients enrolled in Danish national registries. Bonde and his team correlated the clinical outcomes of these patients, all of whom were taking warfarin, with the quality of anticoagulation control achieved during their first six months of treatment.
In an editorial comment linked to the study, Antonio Raviele, MD, said the question of whether to switch AFib patients who are optimally anticoagulated on warfarin to DOACs is one that persists in the medical community. While VKAs like warfarin can cut a patient’s risk of future stroke or mortality, they can also be unpredictable, have a limited therapeutic window and carry a host of food-drug and drug-drug interactions.
“Moreover, it requires routine coagulation monitoring and frequent dose adjustments, resulting in substantial risk and inconvenience,” Raviele, of the Alliance to Fight Atrial Fibrillation in Mestre-Venice, Italy, wrote. “This explains the low use and the high discontinuation rate of warfarin in the real world, as well as the inadequate level of anticoagulation reached in many patients."
DOACs, on the other hand, are much newer and typically come with fewer intracranial hemorrhages, more predictable responses and fewer adverse drug reactions. Those factors allow DOACs to be administered in fixed doses, without the need for routine coagulation monitoring.
Bonde and his team analyzed a total of 4,772 Danish patients, 35.4 percent of whom had good initial anticoagulation control and 64.6 percent of whom had poor control. The former group was defined by a TTR of 70 percent or greater.
During the first year of follow-up, the researchers found that just more than half of patients in the “good control” cohort continued to have a TTR of greater than 70 percent, and those patients’ risk of stroke and major bleeding remained around the same as those with less optimal anticoagulation control. Those with lower TTR values tended to be female, younger than 60 years old, abuse alcohol and have heart failure or peripheral artery disease.
“These results are interesting and have several important clinical limitations,” Raviele wrote. “They show that the optimal management of VKAs for stroke prevention is still a challenge in daily clinical practice.”
They also confirm recently reported data that INR instability is common during follow-up of AFib patients with previously adequate anticoagulation control, he said, and show for the first time that a high TTR value of greater than 70 percent during the first six months of VKA isn’t actually associated with a decreased risk of stroke or bleeding.
Raviele said the results could be explained in part by the way researchers calculate TTR, using an approach known as the Rosendaal method. That method assumes INR values change linearly between successive checks, producing estimated TTRs that are likely “falsely low.”
“Should we abandon the common practice of using a high TTR value to identify patients with atrial fibrillation who will do well on VKAs and do not need to switch to a DOAC, as recommended by current guidelines?” he wrote. “The paper by Bonde et al. seems to suggest that we should. However, it is likely that better patient education, more frequent INR monitoring, prompt VKA dose adjustment and the accurate selection of appropriate candidates for VKA therapy on the basis of TTR predictors would yield a better outcome than that found in the Danish study.”
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.