Source: Am J Med Genet  |  Posted 7 years ago

By Cameron Johnston

WASHINGTON, DC -- October 11, 2004 -- A large study looking at the long-term use of raloxifene (Evista) has shown an increased risk of venous thromboembolic events almost twice that of what was seen in women who were not using the anti-osteoporosis drug.

The results of a long-term extension trial were presented recently at the annual meeting of the North American Menopause Society by Cheryl Keech, MD, PhD, a clinician investigator with Eli Lilly and Company.

In an earlier 4-year study (Multiple Outcomes of Raloxifene Evaluation (MORE) a small percentage of women were seen to have an increased risk of VTE, mainly within the first 4 months of initiating therapy. That trial involved just over 7000 women and was designed to test raloxifene's efficacy in preventing osteoporosis. When that trial had ended, it was decided to launch a similar study, involving the same women to determine whether raloxifene had any impact in preventing breast cancer. To that end, 4011 women from the original trial were recruited to continue treatment. Women who received the placebo in the original trial also received placebo in the continuation study (n=1286), and those who received raloxifene in the original trial also received it in the continuation study (n=2725) (60 mg/day). The mean length of time between ending the original trial and resuming treatment with raloxifene was just over 10 months.

The mean age of the women in the continuation study was 70 years, and one-quarter had already used hormone therapy. They were a fairly healthy group said Dr. Keech. Mean BMI was 25.2 and only 16% were present smokers.

Of all participants who completed both studies, there were 60 VTEs in all, 1.01% in the placebo group and 1.72% in the study group. The annualized rate of VTE in the study group was 0.22%. However, for the second Continuing Outcomes Relevant to Evista (CORE) study, 28 women reported 34 VTEs ? 5 in the placebo group and 23 in the study group (0.29%).

The excess rate of VTEs amounts to 1.6 per 1000 per women-years.

Broken down as to type of event, 17 women in the study group experienced deep vein thrombosis and 9 had pulmonary embolisms, and 2 had RVTs.

The increase in risk for VTE was statistically non-significant, but clinically relevant, the investigators reported. Interestingly, there were no events within the first 4 months of re-initiating treatment, whereas in the original trial, this 4-month period was where most of the events occurred.

The findings are clinically important in that any kind of VTE is considered an emergency. They confirm the recommendations following the first trial, namely, that women with any kind of history of VTEs not be treated with raloxifene, and that the drug should be temporarily discontinued in any woman who is going through a period where she is immobilized, such on bedrest, since inactivity is a prime risk factor for the onset of VTEs.

[Presentation title: Venous Thromboembolic Events in Women Re-Initiating Raloxifene Therapy: Results from the Continuing Outcomes Relevant to Evista (CORE) Trial Abstract: LB16]