Background

Venous thromboembolism (VTE) is a condition in which a blood clot forms in the deep veins of the leg or pelvis (deep vein thrombosis (DVT)), or the clot travels in the blood and blocks a blood vessel in the lungs (pulmonary embolism (PE)). People with a VTE are treated with an anticoagulant, which prevents formation of further clots. For patients with a VTE that has been caused by a certain risk factor (prolonged periods of immobility, cancer, pregnancy, oral contraceptives, hormone replacement therapy, trauma, or blood disorder), treatment can be safely discontinued after three months. However, for patients in whom the VTE has no known cause (unprovoked), the optimal length of treatment is unknown because evidence is limited. Doctors have to decide upon extended treatment based on benefit (i.e. prevention of VTE recurrence) and risk (i.e. of bleeding) associated with treatment. This review assessed whether extended treatment was safe and effective in preventing further clots in patients with an unprovoked VTE.

Study characteristics and key results

We found six studies with a combined total of 3436 patients (until March 2017). Five studies compared treatment with placebo, and one study compared one type of treatment with another. Three of the five studies that used a placebo used warfarin, and two used aspirin. Combining results of the five studies showed no clear difference in the rate of further clots between patients treated with an anticoagulant and those treated with a placebo, and no clear difference in the numbers of deaths, bleeding incidents, or adverse effects such as stroke or heart attack.

One study showed that oral treatment with the anticoagulant rivaroxaban was associated with fewer clots than aspirin. There was no evidence of a difference in major and non-major bleeding events between rivaroxaban and aspirin. Data on deaths and deaths related to clots in the lungs, stroke, and heart attack were not yet available for participants relevant to this review and will be incorporated in a future version of the review.

Quality of the evidence

The quality of the evidence provided by studies included in this review ranged from low to moderate because a small number of studies with few events were included.

This review found that trials are too few to show whether extended treatment is safe and effective in preventing further blood clots after three months’ treatment. Further good-quality and large-scale studies are required.