Lowering the intensity of oral anticoagulant therapy: effects on the risk of hemorrhage and thromboembolism

Abstract

Background: Oral anticoagulation is effective in the prevention of arterial thromboembolism. The major drawback of coumarin therapy is the increased risk of hemorrhage. Implementing the optimal intensity of oral anticoagulation, ie, the level at which thromboembolic events are prevented without introducing an excessive bleeding risk, is an important step to improve the safety of oral anticoagulant therapy.

Methods: We observed all patients of the Leiden Anticoagulation Clinic who were treated because of a mechanical heart valve or atrial fibrillation between January 1, 1995, and January 1, 1998, or because of cerebral ischemia between January 1, 1994, and January 1, 1998. In 1996, at the halfway point of follow-up, the target intensity for patients with a mechanical heart valve was lowered from 4.0 (range, 3.6-4.8) to 3.5 (range, 3.0-4.0) international normalized ratio, and for atrial fibrillation and cerebral ischemia, from 3.5 (range, 3.0-4.5) to 3.0 (range, 2.5-3.5) international normalized ratio. We compared incidence rates of hemorrhage and thromboembolism before and after the introduction of lower target intensities.

Results: Higher target treatments were given to 2341 patients (2863 patient-years) and lower target treatments to 2256 patients (2260 patient-years). After introduction of the lower target ranges, the overall incidence rate of major untoward events declined from 5.7 (95% confidence interval [CI], 4.9-6.7) to 3.6 (95% CI, 2.8-4.4) per 100 patient-years. The incidence of major bleeding fell from 3.6 (95% CI, 2.9-4.4) to 2.7 (95% CI, 2.1-3.5) and the incidence of major thromboembolism from 2.0 (95% CI, 1.5-2.5) to 0.8 (95% CI, 0.5-1.3) per 100 patient-years.

Conclusion: Implementation of lower target intensities for coumarin therapy decreased the complication risk.