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. 2023 Apr 7;44(14):1231-1244.
doi: 10.1093/eurheartj/ehac776.

Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score

Maria A de Winter  1 , Harry R Büller  2 , Marc Carrier  3 , Alexander T Cohen  4 , John-Bjarne Hansen  5 , Karin A H Kaasjager  1 , Ajay K Kakkar  6 , Saskia Middeldorp  7 , Gary E Raskob  8 , Henrik T Sørensen  9 , Frank L J Visseren  10 , Philip S Wells  3 , Jannick A N Dorresteijn  10 , Mathilde Nijkeuter  1 ; VTE-PREDICT study group
Collaborators, Affiliations

Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score

Maria A de Winter et al. Eur Heart J. .

Erratum in

Abstract

Aims: Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation.

Methods and results: Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48-0.71 (recurrence) and 0.61-0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% -19% for bleeding.

Conclusion: The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making.

Keywords: Anticoagulants; Haemorrhage; Prediction model; Recurrence; Risk; Venous thromboembolism.

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Conflict of interest statement

Conflict of Interest: Marc Carrier reports research funding from BMS, Leo Pharma, and Pfizer, and honoraria from Bayer, Sanofi, BMS, Leo Pharma, Servier and Pfizer. All fees are paid to his institution. Ander Cohen reports grants or contracts, consulting fees and payment or honoraria from Bayer AG, Daiichi Sankyo, BMS/Pfizer, and AstraZeneca. All fees were paid to his company. Alfredo Farjat was a full-time employee at Thrombosis Research Institute when he collaborated with this study. Akos Ference Pap is an employee of Bayer AG. Samuel Goldhaber reports grants or contracts from Bayer, Boston Scientific BTG EKOS, NHLBI, BMS, Janssen and Pfizer, consulting fees from Agile, Pfizer, Bayer, speaker fees from Lankenau Grand Rounds in Medicine, Bakken Symposium -University of Minnesota, The Brigham Board Review in Critical Care ‘Virtual Studio/Distance Learning’, New York Cardiovascular Symposium, Latin American Anticoagulation Series Conference, Jeresaty Symposium—Trinity Health of New England, Rutgers New Jersey Medical School Grand Rounds, SBACV Symposium—Brazil Society of Angiology and Vascular Medicine, Brigham-Sheba Collaboration on Thrombosis and Vascular Medicine and Philippine Society of Vascular Medicine Annual Convention. Michael Grosso is an employee of Daiichi Sankyo. Ajay Kakkar reports grants from Bayer AG, Sanofi SA, personal fees from Anthos Therapeutics, Bayer AG, Sanofi S.A. Karen Pieper reports consulting fees from Cryolife, J&J Pharmaceuticals, Artivion and Element Science. Gary Raskob reports consultancy fees or honoraria from AMAG Pharma, Anylam, Anthos Therapeutics, Bayer HealthCare Pharmaceuticals Inc., Bristol-Myers Squibb, Daiichi Sankyo Inc., Janssen Global Services LLC, Pfizer, and XaTrek; honoraria from BMS, Pfizer, Daiichi Sankyo; DSMB or advisory board membership from Anthos Therapetuics, Janssen, Bristol-Myers Squibb and Pfizer, leadership or fiduciary role in other board, society, committee or advocacy group of OU Health, stock or stock option ownership for AbbVie, Inc., Gilead Sciences Inc, GlaxoSmithKline, LLC., LLY, MRK, and Pfizer. Sam Schulman reports research grants, paid to his institution, from Octopharma, and consulting fees from Alexion, Bayer, Boehringer–Ingelheim, Sanofi, Daiichi Sankyo and Octopharma. Minggao Shi is an employee of Daiichi Sankyo. Phillip Wells reports grants and speaker fees from BMS/Pfizer, consulting fees from Anthos and speaker fees and consulting fees from Bayer Healthcare. All fees are paid to his institution. The other authors have nothing to declare.

Figures

Structured Graphical Abstract
Structured Graphical Abstract
BMI, body mass index; DOAC, direct oral anticoagulant; DVT, deep venous thrombosis; Hb, haemoglobin; SBP, systolic blood pressure; VKA, vitamin K antagonist; VTE, venous thromboembolism.
Figure 1
Figure 1
Calibration plots for the VTE-PREDICT model for recurrent venous thromboembolism in external data sets. The study population is divided into 5 or 10 equal groups (depending on population size) based on the predicted risk of recurrent venous thromboembolism according to the VTE-PREDICT risk score and plotted against observed incidences in the same time frame. The longest available follow-up duration is used
Figure 2
Figure 2
Calibration plots for the VTE-PREDICT model for bleeding in external data sets. The study population is divided into 5 or 10 equal groups (depending on population size) based on predicted risk of bleeding according to the VTE-PREDICT risk score and plotted against observed incidences in the same time frame. The longest available follow-up duration is used
Figure 3
Figure 3
Individual absolute recurrence risk reduction and increase in risk of bleeding with extended anticoagulation. If recurrent venous thromboembolism is considered to be as severe as clinically relevant bleeding, the benefit of extended anticoagulation with the full dose of a direct oral anticoagulant outweighs the harm for 77.2% of patients
Figure 4
Figure 4
An individual patient example of the VTE-PREDICT risk score to predict the treatment effects of various extended antithrombotic treatment strategies. Estimates for reduced dose direct oral anticoagulants should be interpreted with caution as the pooled treatment effect is partly based on a comparison between reduced-dose direct oral anticoagulants and aspirin rather than reduced dose direct oral anticoagulants vs. placebo alone (see Supplementary material online, Table S6)
Figure 5
Figure 5
Screenshot of the VTE-PREDICT calculator. Screenshot fromhttps://vtepredict.com
See this image and copyright information in PMC

Comment in

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