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Anticoagulation Control on Warfarin Weakens After 6 Months

— But patients hitting TTR target still had fewer events

Last Updated September 14, 2018
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Atrial fibrillation (Afib) patients on vitamin K antagonist (VKA) therapy often lost good coagulation control after the first 6 months, according to a Danish study aiming to assess real-world treatment.

Only 35.4% of patients who stayed on VKAs for 6 months after drug initiation during 1997-2011 had time in therapeutic range (TTR) ≥70% -- the guideline-endorsed marker of quality anticoagulation, defined as days with an international normalized ratio [INR] between 2.00 and 3.00.

Among those who met this therapeutic target at 6 months, only 55.7% maintained it while staying on VKAs for another 12 months, Anders Nissen Bonde, MD, of Copenhagen University Hospital Herlev and Gentofte, and colleagues reported in the Sept. 18 issue of the .

This means that having good TTR at first had limited long-term prognostic value, according to the investigators. Their study was based on data from several Danish registries.

The results indicate that physicians should not abstain from switching to a DOAC (direct oral anticoagulant) based only on a TTR ≥70%, contradicting what the guidelines say, according to Bonde's team.

Their study included 4,772 Afib patients with serial INR readings no more than 50 days apart. Some INR values were missing, however.

Median TTR was 66.6% among experienced VKA users, meaning that the group had overall "suboptimal anticoagulation control," the researchers said.

Yet clinicians shouldn't simply abandon the recommended practice of using TTR to identify patients with Afib who will do well on VKAs, suggested Antonio Raviele, MD, of Italy's Alliance to Fight Atrial Fibrillation, in an .

"[I]t 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," Raviele wrote.

Whether or not patients had TTR reach 70% in the first 6 months of VKA therapy did not matter in terms of risk of stroke/thromboembolism (HR 1.14 for TTR <70% versus at or above 70%, 95% CI 0.77-1.70) or major bleeding (HR 1.12, 95% CI 0.84-1.49) over the next 12 months.

However, after adjusting for changes in TTR during subsequent follow-up, TTR <70% was in fact associated with an increased risk of stroke/thromboembolism (HR 1.91, 95% CI 1.30-2.82) and major bleeding (HR 1.34, 95% CI 1.02-1.76), Bonde's group found.

"Undoubtedly, DOACs are particularly attractive for Afib patients starting anticoagulant therapy," said Raviele. He cited advantages over VKAs such as fewer intracranial hemorrhages, more predictable response, rapid onset/offset of action, and fewer drug-drug interactions.

With the high cost, however, it isn't clear that Afib patients who are well anticoagulated on warfarin should switch to a DOAC, Raviele indicated.

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    Nicole Lou is a reporter for ֱ, where she covers cardiology news and other developments in medicine.

Disclosures

Bonde and Raviele reported no conflicts of interest.

Primary Source

Journal of the American College of Cardiology

Bonde AN, et al “Outcomes among patients with atrial fibrillation and appropriate anticoagulation control” J Am Coll Cardiol 2018; DOI: 10.1016/j.jacc.2018.06.065.

Secondary Source

Journal of the American College of Cardiology

Raviele A “Should we switch patients who appear to be optimally anticoagulated on warfarin to DOACs?” J Am Coll Cardiol 2018; DOI: 10.1016/j.jacc.2018.06.068.