March 4, 2008Open Access
Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication for anticoagulation was based
Structured PICO
Does the presence of clinical trial exclusion criteria increase the risk of bleeding in patients receiving vitamin K antagonists?
P
Population
1,986 patients receiving vitamin K antagonists, comprising 993 patients hospitalized for bleeding (cases) and 993 matched control patients hospitalized for an infection.
I
Intervention
Presence of one or more exclusion criteria from the original clinical trials that established the indication for anticoagulation.
C
Comparator
Absence of clinical trial exclusion criteria.
O
Outcome
Hospitalization for bleeding (risk of hemorrhage associated with exclusion criteria).safety
Patients prescribed vitamin K antagonists who would have been excluded from the foundational clinical trials have a significantly higher risk of major bleeding, highlighting the need for careful risk-benefit assessment in real-world populations.
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.