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Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication
Marcel Levi1, G Kees Hovingh, Suzanne C Cannegieter
1Department of Internal Medicine/Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.m.levi@amc.uva.nl
Insights
Vitamin K antagonists (VKAs) are widely used for cardiovascular disease. However, many patients prescribed VKAs, especially those experiencing bleeding, wouldn't qualify for clinical trials, increasing hemorrhage risk.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Vitamin K antagonists (VKAs) are standard antithrombotic treatments for cardiovascular disease.
- Clinical trials underpinning VKA guidelines often excluded a significant patient population.
- Real-world VKA use frequently extends to patients with characteristics that would have excluded them from pivotal trials.
Purpose of the Study:
- To assess the eligibility of VKA-treated patients hospitalized for bleeding or infection in clinical trials.
- To evaluate the risk of hemorrhage associated with trial exclusion criteria in VKA users.
Main Methods:
- A case-control study involving 993 patients hospitalized for VKA-related bleeding (cases) and 993 matched controls hospitalized for infection.
- Analysis of patient eligibility for VKA clinical trials based on documented exclusion criteria.
- Estimation of bleeding risk associated with specific exclusion criteria.
Main Results:
- Approximately 23% of control patients met trial exclusion criteria, supporting their anticoagulation.
- Forty percent of patients hospitalized for bleeding met trial exclusion criteria.
- A single exclusion criterion increased bleeding risk 2.9-fold; multiple criteria significantly elevated this risk.
Conclusions:
- VKAs are frequently prescribed to patients ineligible for clinical trials.
- Patients with exclusion criteria face a substantially higher risk of bleeding.
- Careful risk-benefit assessment is crucial when prescribing VKAs to patients who wouldn't qualify for clinical trials.
Abstract:
Vitamin K antagonists (VKAs) are effective antithrombotic agents and advocated in guidelines for the management of cardiovascular disease. However, in the trials underlying these guidelines, many patients were excluded. We performed a case-control study in 993 patients receiving VKAs, who required hospitalization for bleeding, and contrasted them to 993 matched control patients on VKAs, who were hospitalized for an infection. We analyzed whether patients and controls would have been eligible for the clinical trials on which their indication for anticoagulation was based, and estimated the risk of hemorrhage associated with exclusion criteria as applied in those trials. Approximately one quarter (23% [95% CI: 21%-26%]) of controls had one or more exclusion criteria for the trials, supporting the use of anticoagulation for their condition. Forty percent of patients presenting with bleeding had one or more exclusion criteria (95% CI: 37%-43%). Having one exclusion criterion resulted in a 2.9-fold increased risk of bleeding (95% CI: 2.2-3.9), and this risk increased sharply when more than one exclusion criterion was present. VKAs are often prescribed to patients who would not have qualified for clinical trials, and in these patients a careful consideration should be made regarding the expected efficacy and the risk of bleeding.
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