Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management studyBMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j1065 (Published 17 March 2017) Cite this as: BMJ 2017;356:j1065
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Re: Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study
I thank Dr. Middeldorp and Dr. Iorio for drawing attention to the important issue of classification of venous thromboembolism (VTE).
In the REVERSE I study we chose to include women with estrogen associated VTE in the derivation of our clinical decision rule to identify patients at low risk of recurrent VTE who could safely discontinue anticoagulants because exogenous estrogen use is a weak risk factor for VTE (1).
To classify estrogen associated VTE as "provoked", as suggested by Middeldorp and Iorio, would imply that women with estrogen associated clots can’t be further stratified into low (<5% at 1 year off of anticoagulants) and high risk groups (>5% at 1year off of anticoagulants). In other words, there is no point in trying to risk stratify women with estrogen associated VTE because they are all "low risk" (i.e. safe to discontinue anticoagulants). This is not the case.
In Reverse I, we showed that HERDOO2 was able to importantly further stratify women with estrogen associated VTE into low risk (1.3% (0.2-2.4%) annualized risk of recurrent VTE) and high risk groups (10.4% (6.2-14.5%) annualized risk of recurrent VTE) (1).
In Reverse II, 74/397 (19%) women with estrogen associated VTE were high risk by HERDOO2 (65/74 (88%) continued anticoagulants) (2).
Identifying these high risk women who had estrogen associated VTE is important so that they may be given the option of continuing anticoagulants.
Marc Rodger MD MSc (Epidemiology)
Professor and Chief, Division of Hematology, Ottawa Blood Disease Center, Department of Medicine, The Ottawa Hospital, University of Ottawa
University of Ottawa Chair in Venous Thrombosis and Thrombophilia
Heart and Stroke Foundation of Ontario Career Scientist
Senior Scientist, Clinical Epidemiology Program, Ottawa Hospital Research Institute
1812-E Box 201, 501 Smyth Rd, Ottawa, Ontario, CANADA, K1H 8L6
1. Rodger MA, Kahn SR, Wells PS, et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008;179(5):417-26.
Competing interests: No competing interests
Should women with VTE related to oral contraceptive use be regarded as having unprovoked VTE? Questioning the HERDOO2 inclusion criteria.
Decisions on whether to stop or continue anticoagulation in patients with venous thromboembolism pose a day to day challenge for doctors and patients. We read with interest the validation study of the HERDOO2 , in which “low-risk women” based on this algorithm discontinued oral anticoagulants.1 We would like to congratulate the authors with their persistence to complete this management study. However, we would like to question the definition of unprovoked VTE.
For the HERDOO2 algorithm, women with hormone use-related VTE are considered to have unprovoked VTE.1 We are of opinion that oral contraceptive use at the time of VTE should be regarded as (removable) provoking factor. In the HERDOO2 study, women below 50 years of age who had a hormone use-related first VTE had a recurrence rate of 1.4% (0.4-3.7), which was not different from the 3.1% (0.8-7.9) in women who did not have a hormonal provoking risk factor. Also, in the REVERSE study the risk of recurrent VTE in oral contraceptive users or non-users was not found to be statistically different (RR 0.6; 95%CI 0.1 to 2.8).2 It is important to note that these point estimates are in line with an individual patient data meta-analysis3 and with a recent large data linkage observational study4; these larger studies found significantly lower risk of recurrence for women not restarting oral contraceptives after the first event (HR of 0.5, 95% CI 0.3-0.8, and adjusted HR of 0.71; 95%CI 0.58–0.88, respectively). Hence, we would not consider these women to have an unprovoked VTE, but a removable provoking risk factor, and would advise them to seek alternative contraceptive methods prior to discontinuing anticoagulant therapy after 3 months.
1. Rodger MA, Le Gal G, Anderson DR, et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study. Bmj. 2017;j1065.
2. Le Gal G, Kovacs MJ, Carrier M, et al. Risk of recurrent venous thromboembolism after a first oestrogen-associated episode. Data from the REVERSE cohort study. Thromb. Haemost. 2010;104(3):498–503.
3. Douketis J, Tosetto A, Marcucci M, et al. Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis. BMJ. 2011;342:d813.
4. Kiconco S, Abdul Sultan A, Grainge MJ. Recurrence risk of venous thromboembolism and hormone use in women from England: a cohort study using clinical practice research datalink. Br. J. Haematol. 2017; Jan 20. doi: 10.1111/bjh.14516. [Epub ahead of print]
Competing interests: No competing interests