Determination of the appropriate duration of anticoagulant therapy after venous thromboembolism is governed by the risk/benefit ratio. Physicians often perceive that thromboembolism recurrence has a greater clinical impact than the risk of anticoagulant-induced bleeding, although estimates of the latter are not available. In situations in which extended anticoagulant therapy is unclear, such as patients with idiopathic venous thromboembolism, heterozygous carriers of the factor V Leiden mutation and, possibly, patients with protein S or protein C deficiency, bleeding risk becomes an even more important factor in the decision.
Linkins and associates performed a meta-analysis of studies examining bleeding rates among patients with venous thromboembolism who received at least three months of anticoagulant therapy with a target International Normalized Ratio of 2 to 3. Randomized or prospective cohort studies of patients with confirmed thromboembolism who received a coumarin derivative and were monitored for bleeding events were reviewed.
Thirty-three studies involving 10,757 patients who received 4,374 patient-years of anticoagulant therapy were included. Major bleeding occurred at a rate of 7.22 per 100 patient-years, and fatal bleeding occurred at a rate of 1.31 per 100 patient-years. Intracranial bleeding occurred at a rate of 1.15 per 100 patient-years, with almost 50 percent being fatal. Major bleeding was more likely to occur in the first three months of treatment. Of the 276 major bleeding episodes in all of the patients receiving anticoagulant therapy, 37 (13.4 percent) were fatal. Thus, the clinical impact of anticoagulant major bleeding is about one in seven.
The authors conclude that information about the risk of major bleeding in patients with venous thromboembolism who are treated with anticoagulants helps to determine appropriate treatment length. In the typical patient with idiopathic venous thromboembolism, the risk of fatal venous thromboembolism recurrence is greater than the risk for fatal bleeding after completion of six months of therapy. Therefore, extended anticoagulation may be useful. In patients with a higher risk of anticoagulant-induced major bleeding, bleeding risks may outweigh the value of extended anticoagulant use. Physicians should consider bleeding risk when making the decision about long-term anticoagulant therapy.