Increased risk of recurrent venous thromboembolism during hormone replacement therapy - Results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial (EVTET)

Recent observational studies suggest a 2-4 fold increased risk of venous th romboembolism (VTE) in women taking hormone replacement therapy (HRT). The present study was started before publication of these studies, and the aim was to determine if HRT alters the risk of VTE in high risk women. The stud y was a randomized, double-blind, and placebo-controlled clinical trial wit h a double-triangular sequential design. Females with previously verified V TE were randomized to 2 mg estradiol plus 1 mg norethisterone acetate, 1 ta blet daily (n = 71) or placebo (n = 69). The primary outcome was recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE). Between 1996 and 1 998 a total of 140 women were included. The study was terminated prematurel y based on the results of circumstantial evidence emerging during the trial . Eight women in the HRT group and one woman in the placebo group developed VTE. The incidence of VTE was 10.7% in the HRT group and 2.3% in the place bo group. In the HRT group, all events happened within 261 days after inclu sion. The sequential design did not stop the study, but strongly indicated a difference between the two groups. Our data strongly suggests that women who have previously suffered a VTE have an increased risk of recurrence on HRT. This treatment should therefore be avoided in this patient group if po ssible. The results also support those of recent epidemiological studies, w hich also indicate increased risk of VTE in non-selected female populations during HRT.