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Center for Global Research Data

Individualized prediction of recurrence risk reduction and risk of bleeding with extended anticoagulation in patients with venous thromboembolism

Lead Investigator: Mathilde Nijkeuter, UMC Utrecht
Title of Research Proposal: Individualized prediction of recurrence risk reduction and risk of bleeding with extended anticoagulation in patients with venous thromboembolism
Vivli Data Request: 5951, 4543
Funding Source: Employment Contracts – UMC Utrecht
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and pulmonary embolism (PE). In DVT, a blood clot blocks a vein in the leg, whereas in PE, a vessel in the lungs is blocked. VTE is the third most frequent cardiovascular disease, occurring in 1-2 per 1000 people annually. Anticoagulation for a minimum of 3 months is the mainstay of therapy. After the initial 3 months, a decision should be made to stop anticoagulation or to continue to prevent recurrent VTE, with consideration of the patient’s preferences. As prior duration of treatment after the first 3 months does not influence risk of recurrence, it is advised to either stop or continue indefinitely[4]. Indefinite anticoagulant treatment, which is advocated in the absence of a high risk of bleeding, minimizes the risk of recurrent VTE, but requires lifelong compliance and gives an annual 1-2% risk of major bleeding. These major bleedings comprise, among others, intracranial bleeds and bleeding of an internal organ.

In daily clinical practice, it is difficult to decide whether to continue or stop treatment, because both risk of recurrence and risk of bleeding differ between individuals. Several risk scores for bleeding and recurrent VTE have been developed. With a moderate predictive accuracy and methodological limitations, guidelines and recent reviews do not recommend using these scores. Thus, how to weigh risk of bleeding and risk of recurrent VTE for individual patients remains an important clinical dilemma worldwide. Inadequate risk assessment can lead to unfavorable treatment choices, increasing risk of recurrent VTE and bleeding. Moreover, personalized information on risks and benefits of treatment is required to enable patient involvement and shared decision-making, which will increase patient satisfaction with care and treatment adherence while reducing costs.

In the proposed project, we will combine data from existing international data from large cohorts and trials on VTE. Using this data, we will develop models for the prediction of recurrent VTE within 5 years after stopping anticoagulation, and for the prediction of bleeding during 5 years of anticoagulation, after the initial >3 months. With these models, the effect of extended anticoagulant treatment with different types of anticoagulants can be predicted for individual patients. Our aim is to develop a well performing prediction model that is simple to use in clinical decision making with individual patients. The statistical methods used will be similar to those used in previous analyses of our group. Our models will be integrated in a web-based, online calculator on https://U-Prevent.com, which is developed by group members Frank Visseren and Jannick Dorresteijn. It already includes 11 interactive calculators of cardiovascular prediction models, and is increasingly used worldwide by physicians and their patients.

The proposed model will have the potential to assess an individual’s risk of recurrent VTE as well as the risk of major and clinically relevant bleeding. These individual risks can be used to decide on treatment duration by weighing individual thresholds for treatment via shared decision-making. This will improve patient satisfaction and adherence to medication. Moreover, overtreatment as well as undertreatment can be prevented and reduce the worldwide burden of VTE-related and bleeding-related morbidity and mortality.

Requested Studies:

A Phase 3, Randomized, Parallel-Group, Multi-Center, Multi-National Study for the Evaluation of Efficacy and Safety of (LMW) Heparin/Edoxaban Versus (LMW) Heparin/Warfarin in Subjects With Symptomatic Deep-Vein Thrombosis (DVT) and or Pulmonary Embolism (PE).
Sponsor: Daiichi Sankyo, Inc.
Study ID: NCT00986154
Sponsor ID: DU176b-D-U305

A Phase III, Randomised, Multicenter, Double-blind, Parallel-group, Active Controlled Study to Evaluate the Efficacy and Safety of Oral Dabigatran Etexilate (150 mg Bid) Compared to Warfarin (INR 2.0-3.0) for the Secondary Prevention of Venous Thromboembolism.
Sponsor: Boehringer Ingelheim
Study ID: NCT00329238
Sponsor ID: 1160.47

Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long-term Prevention of Recurrent Symptomatic Proximal Venous Thromboembolism in Patients With Symptomatic Deep-vein Thrombosis or Pulmonary Embolism.
Sponsor: Boehringer Ingelheim
Study ID: NCT00558259
Sponsor ID: 1160.63

(Note: Additional study added as part of data request 5951)

Prevention of Thromboembolic Events – European Registry in Venous Thromboembolism (PREFER in VTE)
Sponsor: Daiichi Sankyo, Inc.
Study ID: DRKS00004795
Sponsor ID: DSE-VTE-01-12