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21 Dec 2006:
Raloxifene (Evista®) and risk of venous thomboembolism / fatal stroke

Raloxifene (Evista® 60mg, Eli Lilly) is a selective estrogen-receptor modulator (SERM) that binds to the estrogen receptor, leading to estrogen-agonist effects in some tissues and estrogen-antagonist effects in others. The drug has been approved in Singapore since 1999 and is licensed for the treatment and prevention of osteoporosis in postmenopausal women.

In July 2006, The New England Journal of Medicine published the results of the Raloxifene Use for the Heart (RUTH) Study, designed to investigate possible cardioprotective effects of raloxifene in the elderly. The results suggest that raloxifene did not demonstrate to protect women against heart disease and could be associated with excess deaths from stroke.


The RUTH study

RUTH was an international, multicentre, randomised, double-blind, placebo-controlled trial. The two primary objectives were to determine the effect of raloxifene as compared with placebo on the incidence of coronary events (i.e. death from coronary causes, nonfatal [including silent] myocardial infarction, or hospitalisation for an acute coronary syndrome other than myocardial infarction) and invasive breast cancer.

A total of 10,101 postmenopausal women (mean age, 67.5 years) with coronary heart disease (CHD) or multiple risk facts for CHD were randomly assigned 60mg of raloxifene or placebo and followed for a median of 5.6 years and the median exposure to the study drug was 5.05 years.


Primary outcomes

There was no significant difference between raloxifene and placebo group in the risk of primary coronary events (533 vs 553 events; hazard ratio, 0.95; 95% confidence interval, 0.84 to 1.07). Compared to placebo, raloxifene reduces the risk of invasive breast cancer (40 vs 70 events; hazard ratio, 0.56; 95% confidence interval, 0.38 to 0.83; absolute risk reduction, 1.2 invasive breast cancers per 1,000 women treated for one year); the benefit was primarily due to a reduced risk of estrogen-receptor–positive invasive breast cancers.


Secondary outcomes

The overall incidence of stroke did not differ significantly between the treatment groups, but raloxifene was associated with an increased risk of fatal stroke (59 vs 39 events; hazard ratio, 1.49; 95% confidence interval, 1.00 to 2.24; absolute risk increase, 0.7 per 1000 woman-years) and venous thromboembolism (VTE) (103 vs 71 events; hazard ratio, 1.44; 95% confidence interval, 1.06 to 1.95; absolute risk increase, 1.2 per 1000 woman-years).

Raloxifene reduced the risk of clinical vertebral fractures (64 vs 97 events; hazard ratio, 0.65; 95% confidence interval, 0.47 to 0.89; absolute risk reduction, 1.3 per 1,000).

There was no significant difference between the treatment groups in the rates of death from any cause or overall death from cardiovascular events.

With these results, the authors concluded that raloxifene did not significantly affect the risk of CHD. The benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risk of venous thromboembolism and fatal stroke.


Local situation

HSA has not received any serious report of VTE or stroke suspected to be associated with raloxifene. The ADR reports submitted pertain to non-serious skin reactions, headache and insomnia.

HSA is working with the product licence holder to amend the local package insert of Evista® to reflect the conclusions of the RUTH study.


Last updated on 02 Jul 2010 16:57:27
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