How to Improve Care for Blood Clots That Can End Up in the Lungs

Venous thromboembolism (VTE) is serious condition that begins with a blood clot in a vein – often in the lower leg – that makes its way to the lungs, causing a pulmonary embolism with potentially fatal consequences. VTE affects between 300,000 to 600,000 Americans every year, making it the third most common vascular diagnosis after heart attack and stroke.

The primary treatment for VTE has been giving anticoagulation therapy (blood thinners) for a period of three to six months. Current guidelines suggest extending this treatment window for some patients with VTE.

VTE treatment options include K vitamin antagonists, primarily warfarin and the more recently developed direct oral anticoagulants (DOACs), which include the direct thrombin inhibitor dabigatran and factor Xa inhibitors. Although DOACs are recommended for the initial treatment phase of VTE, less is known about which anticoagulants are preferred for extended VTE treatment.

In a study publishing August 15, 2023, in JAMA Network Open, researchers from UCSF and Kaiser Permanente, conducted a retrospective cohort study of patients with VTE whose anticoagulant treatment was extended beyond six months after acute VTE. They found that DOAC treatment was associated with a lower risk of recurrent VTE than warfarin.

The study had a total of 18,495 adults with VTE diagnosed between 2010 and 2018 and were treated with at least six months of anticoagulation therapy, of whom 2,134 received DOAC therapy and 16,361 received warfarin therapy. The researchers compared rates of recurrent VTE, hospitalizations for hemorrhage and all cause death among adults prescribed DOACs or warfarin. VTE types studied included pulmonary embolism and deep venous thromboses of the upper and lower extremities, as well as VTE of unusual sites.

Patients were followed from the end of the initial six-month treatment period until discontinuation of anticoagulation or the end of the study follow-up period. After multivariable adjustment, DOAC treatment was associated with lower risk of recurrent VTE but not lower risk for hospitalization for hemorrhage or all cause death, compared with warfarin treatment.

“Our study contributes to the growing evidence supporting the use of DOACs for both initial and extended treatment of VTE in terms of clinical outcomes as well as treatment satisfaction,” said Margaret C. Fang, MD, MPH, study first author and Medical Director of UCSF’s Anticoagulation Clinic. “Future investigation should address the comparative outcomes of reduced dose of DOACs for VTE as well as the optimal duration of treatment for individual patients.”

The researchers believe further study is warranted since patients were not randomly assigned to warfarin or DOAC treatment, so unaccounted factors may have affected the choice of anticoagulant. Because extended anticoagulation is associated with elevated bleeding risk, particularly in older patients, examining outcomes in these patients is important.

“These findings highlight the value of observational studies among large, diverse, real-world populations to complement evidence from randomized controlled trials of VTE prevention strategies in more selected individuals,” said Alan S. Go, MD, study co-author and associate director for the Kaiser Permanente Division of Research and Regional Medical Director for the Kaiser Permanente Clinical Trials Program.
 

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