Extending anti-clotting treatment linked to lower rates of new clots

Extending anti-clotting drugs beyond the initial treatment period of at least 90 days after a first blood clot is linked to lower rates of new clots developing compared with stopping treatment, finds a US study published by The BMJ.

Extended treatment was also linked to higher rates of major bleeding (a common side effect of anti-clotting drugs) but the authors say continued use results in an overall “net clinical benefit.”

Guidelines recommend anti-clotting treatment for at least three to six months for patients with venous thromboembolism (VTE) and extended treatment if the VTE has no obvious underlying cause. But there is limited evidence on optimal treatment duration and the long term risk of bleeding is unclear.

Study methods and design

To address this, researchers drew on information from two national US claims databases for 30,554 patients (average age 74 years; 57% women) taking anti-clotting drugs for a first unprovoked VTE (with no obvious underlying cause or reversible risk factors) for at least 90 days.

Using a technique called target trial emulation, which applies the design principles of randomized trials to observational data, they compared rates of hospital admission for recurrent VTE and major bleeding in patients who continued and discontinued treatment.

The average treatment duration was 357 days in the continued group and 105 days in the discontinued group. Other factors, such as existing conditions and medication use, were also taken into account.

Key findings on risks and benefits

After initial anticoagulation of at least 90 days, compared with patients who discontinued treatment, those who continued treatment had markedly lower (81%) rates of recurrent VTE (equivalent to 26 fewer events per 1,000 person-years) and lower death rates (26%), but higher rates of major bleeding (75%).

Continuing treatment was also associated with a greater net clinical benefit (a combined measure of recurrent VTE and major bleeding) regardless of treatment duration, which persisted among those using anti-clotting drugs for at least three years after VTE.

Study limitations and clinical implications

The authors acknowledge some limitations. For example, the data lacked information on over-the-counter drug use, socioeconomic status, laboratory test results, and reasons for discontinuing anti-clotting drugs, which may have introduced bias.

However, they say this is a large study that used rigorous analytical methods and the results are consistent with previous studies on this topic, which “should help inform decisions on continuation of treatment, which should be individualized for each patient with an unprovoked VTE.”

While this study provides clinicians and patients with good insight into the effectiveness and safety of long-term oral anticoagulation treatment, patient preferences are key to weighing the benefits and risks of indefinite treatment, say researchers from Canada in a linked editorial.

They point out that some uncertainty remains, and say additional research to better identify patients who can benefit from continuing oral anticoagulation treatment after a first unprovoked VTE “will help clinicians counsel and support patients who are faced with the prospect of indefinite anticoagulation treatment.”