Continuing oral anticoagulants (OACs) in unprovoked venous thromboembolism (VTE) beyond the 90-day mark provides substantial protection against VTE recurrence and lowers mortality, benefits that outweigh an increased bleeding risk.

That’s the conclusion of a large target-trial emulation using data from more than 60,000 US patients in Medicare and commercial insurance databases. After propensity score matching, individuals who continued OACs had far fewer recurrent events and lower all-cause mortality than those who stopped, even when treatment was extended well beyond the traditional 3- to 6-month window.

“These results reflect the average effect of continuing OACs and should help inform decisions on continuation of treatment, which should be individualized for each patient with an unprovoked VTE,” investigators led by Kueiyu Joshua Lin, MD, Brigham and Women’s Hospital, Harvard Medical School, Boston, wrote.

The findings were published online on November 12 in The BMJ.

‘Greater Net Clinical Benefit’

Current guidelines recommend at least 3-6 months of anticoagulation for VTE and longer treatment for unprovoked events, but uncertainty about long-term bleeding risk has persisted. In practice, many clinicians have traditionally stopped therapy after that 3- to 6-month window because earlier trials were too small to define long-term safety and largely excluded frail, real-world patients, leaving the true balance of benefit and harm unclear.

Although earlier randomized trials showed that extended therapy reduced recurrent VTE, the investigators noted that these studies were underpowered to detect differences in major bleeding and lacked the follow-up needed to define a true risk-benefit profile. These trials also enrolled highly selected populations, raising questions about how well their findings applied to frail, real-world patients — one reason many clinicians have continued to stop anticoagulation after the traditional 3- to 6-month window.

The current cohort study included data from two US nationally representative databases — Medicare and Optum Clinformatics Data Mart — for 30,554 propensity score-matched pairs (mean age, 74 years; 57% women) who had initiated warfarin or direct OACs within 30 days of hospital admission for a first unprovoked VTE and continued treatment for at least 90 days.

The investigators applied the principles of randomized trials to observational data in a target trial emulation design to compare the participants who extended OAC use after the initial 90-day period (average treatment duration, 357 days) with those who discontinued use soon after (average treatment duration, 105 days).

The co-primary outcomes were hospital admission for recurrent VTE, to measure treatment effectiveness, and major bleeding events. Secondary outcomes included recurrent VTE plus bleeding (net clinical benefit) and mortality.

Results showed that participants who continued OACs beyond the initial 90-day course had significantly lower rates of recurrent VTE than those who discontinued (adjusted hazard ratio [aHR], 0.19; adjusted rate difference, -25.5 per 1000 person-years). Most recurrent events were pulmonary emboli (74%) and the remainder deep vein thromboses.

The continuing OAC group also had higher rates of major bleeding (aHR, 1.75; adjusted rate difference, 4.78), lower rates of mortality (aHR, 0.74; adjusted rate difference, -14.31), and greater net clinical benefit (aHR, 0.39; adjusted rate difference, -21.01).

“The greater net clinical benefit was consistent across OAC types and length of initial OAC treatment,” even beyond 1080 days, the investigators wrote.

Shared Decision-Making

In an accompanying editorial, Miriam Kimpton, MD, and Tzu-Fei Wang, MD, both from the University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada, noted that the study provides “further real-world data” to help determine risk and benefit from indefinite anticoagulation in this patient population — and applauded its long-term follow-up data.

“The results from this study are consistent with previous studies on this topic and do support the use of continued oral anticoagulation,” Kimpton and Wang wrote.

Still, they also cited several study limitations, including the use of retrospective databases and that the risk-benefit calculations may not translate to a better quality of life for patients, consider their preferences, or determine the cost-benefit ratio to healthcare systems.

“Such perspectives are beyond the scope of this study but can be important for further investigations,” they wrote.

The editorialists emphasized that discussions with patients about preferences for treatment duration and even type of anticoagulant are paramount for clinicians.

“We should have been engaging with patients in the decision-making all along,” Wang, who is an associate professor in the Division of Hematology at The Ottawa Hospital, told Medscape Medical News.

“Certainly, every individual is different and may have different medical conditions and social situations that could be important, such as whether they can afford these medications,” she said.

She added that because every patient has a different perspective, “it’s our job to provide them data and then make decisions together.”

The study was funded by a National Institute on Aging grant and by investigator support from the Eliot B. and Edith C. Shoolman Fund of the Massachusetts General Hospital and a Patient-Centered Outcomes Research Institute Project Program Reward. The other investigators and editorialists reported having no relevant financial relationships.