Background: A prospective multicenter study conducted by the British Thoracic Society in 1992 concluded that three months of anticoagulation therapy was appropriate following a first deep venous thrombosis (DVT) or pulmonary embolism, as well as for patients who had a three-year interval or longer since a previous episode. However, most experts continue to recommend anticoagulation therapy for at least six months following an episode of DVT or pulmonary embolism. The British Thoracic Society conducted a second multicenter study from 1999 to 2002 to obtain additional evidence to support its previous recommendation for shorter periods of anticoagulation therapy.
The Study: Adults with probable or confirmed DVT or pulmonary embolism being considered for anticoagulation therapy were recruited from 46 British hospitals. Patients were randomized to three or six months of warfarin (Coumadin) therapy, with target International Normalized Ratios between 2.0 and 3.5. All patients received an initial five days of low-molecular-weight heparin and were treated at the discretion of their physicians. Patients were assessed at three, six, and 12 months from onset of treatment, and any adverse events (i.e., death from DVT or pulmonary embolism, treatment failure, recurrence of thrombosis, or major hemorrhage) were documented.
Results: The 380 patients assigned to six months of anticoagulation therapy had a slightly higher percentage of men and patients with pulmonary embolism than did the 369 patients assigned to three months of therapy. The groups were comparable at randomization. At three months, 13 percent of the three-month group and 11 percent of the six-month group had poor control of anticoagulation. For those continuing therapy up to six months, control of warfarin therapy improved, and only 4 percent had poor control between three and six months.
Overall mortality from DVT or pulmonary embolism was 0.7 percent. One patient in the three-month group died from DVT or pulmonary embolism during treatment, and another patient died one month after completing treatment. Three patients assigned to the six-month group died from DVT or pulmonary embolism during treatment (see accompanying table). In addition, 28 patients from both groups died from other causes during follow-up. The rates of treatment failure or recurrence were similar in the two groups; however, major nonfatal hemorrhage only occurred in patients assigned to the six-month group.
|Outcome||Three-month group (n = 369)||Six-month group (n = 380)|
|Death from pulmonary embolism during or after treatment||2||3|
|Death from hemorrhage during treatment||0||0|
|Death from known other causes during or after treatment||12||16*|
|Unknown outcome at one year||6||4|
|Nonfatal extensions, failures or resolution, or recurrences of DVT or pulmonary embolism||29||26*†|
|Major nonfatal hemorrhages during treatment||0||8†|
|Adverse outcome as a result of DVT or pulmonary embolism or its treatment||31||35|
Conclusion: Three months of anticoagulation therapy for patients who have DVT or pulmonary embolism and do not have any major risk factors (e.g., thrombophilias) is as effective as treatment for six months. It also is associated with a lower incidence of hemorrhage during treatment.