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Identifying Risk Factors of Lower Extremity Venous Thromboembolism, Why DOACs Should be Considered for Anticoagulation

November 11, 2020

By Julie Gould

greg piazzaAccording to new research published online in JAMA, when there is greater recognition of lower extremity venous thromboembolism (VTE), along with advances in anticoagulation, there are improved clinical evaluations and treatment methods for patients with deep vein thrombosis (DVT). However, according to the researchers, in regards to efficacy, direct oral anticoagulants (DOAC) are noninferior to warfarin and lower rates of bleeding. Although, the costs of DOACs often limit patients from utilizing this therapy option.  

“Incidence rates for lower extremity DVT range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from 20% to 36% during the 10 years after an initial event,” the study authors wrote. “This review provides an evidence-based update of the diagnosis and therapy of lower extremity DVT.”

To better understand the findings of the study with spoke with study author Gregory Piazza, MD, MS, director, Vascular Medicine Section, Brigham and Women’s Hospital. Dr Piazza explains that there is growing list of risk factors for venous thromboembolism, such as atherosclerotic cardiovascular disease, and explains why there is an emphasis on the consideration of DOACs for anticoagulation in lower extremity venous thromboembolism.  

What existing data led you and your co-investigators to conduct this research?

The care of patients with venous thromboembolism, including lower extremity deep vein thrombosis, has changed substantially over the last 5-10 years.  The direct oral anticoagulants, or DOACs as they are often called, have become the mainstay of therapy for venous thromboembolism because of the comparable efficacy to warfarin but enhanced safety.  Because DOACs provide clinicians with a greater safety margin than warfarin and because they offer different levels of anticoagulant intensity, anticoagulation can be tailored to a wider population of patients of those with venous thromboembolism.  We wanted to provide an updated “roadmap” for the general clinician regarding the evaluation and management of deep vein thrombosis in this new era of anticoagulation.

Please briefly describe your study and its findings. Were any of the outcomes particularly surprising? 

In our clinical review, we describe the growing list of risk factors for venous thromboembolism, such as atherosclerotic cardiovascular disease.  We highlight the importance of integrating an assessment of these risk factors and pretest probability with laboratory testing, like the D-dimer test, and imaging when appropriate.  Once the diagnosis of deep vein thrombosis is made, we reviewed the approach to anticoagulation, starting with an assessment of risk for adverse outcomes and consideration of those patients who may be treated without hospitalization.  DOACs have emerged as the preferred agent for immediate anticoagulation, as long as cost does not impose undue burden on the patient.  Finally we explore the advancing understanding of risk of recurrence after a venous thromboembolism and discuss the approach to identifying patients who should receive long-term secondary prevention anticoagulation. 

What are the possible real-world applications of these findings in clinical practice? 

We hope that this clinical review will provide clinicians with a real-world approach to the rapid evaluation of patients with suspected deep vein thrombosis, including how to interpret D-dimer results and when to order a venous ultrasound.  We emphasize the consideration of DOACs for anticoagulation in lower extremity venous thromboembolism because of the great safety.  Finally, we hope that our discussion of optimal duration of anticoagulation enables readers to abandon the classification of recurrence risk according to the dichotomy of provoked and unprovoked venous thromboembolism in favor of a more individualized risk assessment. 

Do you and your co-investigators intend to expand upon this research? 

We are conducting further research in long-term secondary prevention for patients with what has traditionally been called provoked venous thrombosis, episodes following an identifiable trigger like surgery or hospitalization for medical illness.  We are conducting the HI-PRO trial which is set to evaluate low-intensity anticoagulation with a DOAC versus placebo in patients with a provoked venous thromboembolic event and at least one enduring predisposing factor (NCT04168203). 

About Gregory Piazza, MD, MS

Dr. Piazza’s research interests include the epidemiology, pathophysiology, diagnosis, treatment, and prevention of venous thromboembolism, thrombophilia-associated infertility, computerized decision support to improve cardiovascular outcomes, as well as stroke prevention in atrial fibrillation. 


Chopard R, Albertsen IE, Piazza G. Diagnosis and Treatment of Lower Extremity Venous Thromboembolism: A Review. JAMA. 2020;324(17):1765-1776. doi:10.1001/jama.2020.17272

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