Graphical Abstract
The balance of shared decision-making in determining the optimal duration of anticoagulation after venous thrombo-embolism.
Study the past, if you would divine the future.
Confucius
The discussion of extended duration anticoagulation for prevention of recurrent venous thrombo-embolism (VTE) has become increasingly complicated over the past decade. First, the algorithmic approach of dichotomizing patients with VTE into categories of provoked and unprovoked has been called into question.[1] Evidence-based clinical practice guidelines now recommend consideration of the circumstances surrounding the VTE as well as enduring risk factors in the decision-making process regarding secondary prevention.[2,3] A shift in anticoagulation preference from vitamin K antagonists to direct oral anticoagulants (DOACs), including low-intensity regimens (such as apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily) with a reduced risk of major bleeding, has further changed the risk–benefit calculation for secondary prevention of VTE. Finally, a greater medical community embrace of shared decision-making, with recognition of patient preferences, long-term risk of bleeding, lifestyle and occupational implications, and the financial burden of extended duration anticoagulation, demands individualized treatment plans.
Current recommendations for determining the optimal duration of anticoagulation categorize patients by risk of VTE recurrence into three categories: low, intermediate, and high.[3] Low-risk patients are distinguished by major provoking factors and a <3% per year risk of recurrence, and receive short-term anticoagulation (typically a minimum of 3 months). In contrast, high-risk patients are characterized by factors associated with a substantially increased risk of recurrence (>8% per year) and frequently receive antithrombotic therapy without a pre-determined end date. Intermediate risk for VTE recurrence (3–8% per year) is a broad category including patients with minor transient provoking factors who may or may not have comorbid conditions contributing to some amount of enduring risk. The optimal duration of anticoagulation remains unclear in many patients who fall into this category, for which there is clinical equipoise regarding stopping or extending antithrombotic therapy. The EINSTEIN (Continued Treatment Study) and EINSTEIN CHOICE trials focused on such patients and demonstrated a net clinical benefit with extended anticoagulation.[4,5] Optimal antithrombotic regimens and durations for patients with enduring risk factors, such as obesity and chronic inflammatory diseases, as well as of those with minor transient risk factors, including long-haul travel, hormonal contraceptive therapy, and acute infectious illness without immobility, remain a focus of intense clinical investigation.[6]
In addition to research focused on optimal intensity and duration of anticoagulation, an emphasis on shared decision-making has also become paramount because of the myriad implications of long-term antithrombotic therapy.[7] While DOACs offer effective and safe options for extended duration anticoagulation for secondary prevention of recurrent VTE,[4,5,8,9] bleeding can still be an important clinical concern.[10] Furthermore, DOACs are not the preferred therapy in certain circumstances, such as antiphospholipid antibody syndrome.[11] Importantly, interactions between medically necessary medications, such as antiplatelet therapy and non-steroidal anti-inflammatory medication, may heighten the risk of bleeding. In addition, patients prioritize outcomes differently, with some more concerned about VTE recurrence and others about major or life-threatening bleeding. Implications of extended duration anticoagulation need to be considered as well. Antithrombotic therapy without a pre-determined end date can have important consequences for lifestyle and employment by precluding certain sports or recreational activities, such as skiing, and careers, such as law enforcement, respectively. Finally, cost remains a critical concern because many patients, especially the elderly and the socioeconomically disadvantaged, may not be able to bear the financial burden of the cost of a lifetime of antithrombotic therapy, especially with a DOAC.[12] Weighing all of these considerations within the confines of increasingly busy clinic schedules frequently forces clinicians into a delicate balancing act.
In this issue of the European Heart Journal, de Winter and colleagues describe the development and validation of the VTE-PREDICT risk score for prediction of 5-year risks of recurrence and bleeding in patients with VTE who have completed at least 3 months of anticoagulation.[13] Using the wealth of individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15 141 patients), the investigators derived the VTE-PREDICT risk score. Validity was then tested in the Danish VTE Cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257). The VTE-PREDICT risk score demonstrated agreement between predicted and observed 5-year risks, with C-statistics up to 0.71 for VTE recurrence and 0.68 for bleeding. The VTE-PREDICT risk score compared favourably with other existing risk stratification tools but offers the advantage of risk assessment for both VTE recurrence and bleeding. Finally, when tested in the large Danish VTE Cohort, the VTE-PREDICT risk score demonstrated that the absolute predicted risk reduction for recurrent VTE exceeded the increase in bleeding risk for 77% of patients, suggesting that extended duration anticoagulation may be the dominant strategy for most patients.
While the C-statistics for recurrent VTE and bleeding are modest for the VTE-PREDICT risk score, clinically useful risk assessment tools typically demonstrate correlation of ≥0.7, as was the case with this model. The ability of the VTE-PREDICT risk score to assess the hazards of both VTE recurrence and bleeding uniquely positions it to assist clinicians and patients in the shared decision-making discussion surrounding extended duration anticoagulation. Integration of both long-term hazards in the risk score supports a greater shift in the literature, including the evidence-based clinical practice guidelines, to acknowledge bleeding as an important consideration when contemplating anticoagulation without a pre-determined end date for secondary prevention of VTE.[14] While the greater safety and convenience of DOAC-based regimens have increased the population of patients in whom extended duration anticoagulation for VTE is feasible, antithrombotic therapy without a pre-determined end date should not be wielded lightly nor prescribed without careful consideration of bleeding, patient preference, and cost.
The VTE-PREDICT Study Group should be commended not only for providing a tool to facilitate shared decision-making around duration of anticoagulation after VTE but also for the method by which this risk score was derived and tested. By using a rich collection of clinical trial and observational cohort studies, the investigators have incorporated an inclusive and rigorous group of datasets that have helped to shape the field of VTE treatment over the past decade. With the VTE-PREDICT risk score, clinicians can now be better prepared to enter into a more balanced shared decision-making discussion that prioritizes patient safety and preferences (Graphical Abstract). Because the VTE-PREDICT Study Group studied the past, we now have a tool that enables us to look to a brighter future—one in which we can more precisely individualize long-term prevention pathways for our patients with VTE.
Data availability
No new data were generated or analysed in support of this research.
Eur Heart J. 2023;44(14):1245-1247. © 2023 Oxford University Press
Copyright 2007 European Society of Cardiology. Published by Oxford University Press. All rights reserved.
