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Hormone therapy drugs ‘increase heart disease risk’

pharmafile | December 10, 2010 | News story | Research and Development | AstraZeneca, Hormone therapy, Novartis, Pfizer, aromatase inhibitors, breast cancer, tamoxifen

Three aromatase inhibitors could increase the risk of heart disease in postmenopausal women with breast cancer, according to new data.

Pfizer’s Aromasin, AstraZeneca’s Arimidex, and Novartis’ Femara have been linked to a greater risk of heart complications than generic alternative Tamoxifen in a new study.

The study, presented at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, showed women are 20% more likely to develop cardiovascular disease when using new aromatase inhibitors, as opposed to an older therapy.

Women who took aromatase inhibitors were 48% more likely to suffer a fracture than those on tamoxifen, regardless of how long they took the medicine, the meta-analysis of seven studies found.

But patients on tamoxifen were more likely to develop endometrial cancer and dangerous blood clots in the legs and use of aromatase inhibitors resulted in a reduced risk for venous thrombosis and endometrial carcinoma, the study showed.

Aromasin, Arimidex and Femara are all aromatase inhibitors, which work by stopping the production of estrogen, a hormone that is shown to fuel cancer growth, especially in breast and ovarian cancers.

These drugs collectively generated over $3.5 billion last year and are often used a second line therapy after tamoxifen.

Eitan Amir, a senior fellow in the division of medical oncology and hematology at the Princess Margaret Hospital, Toronto, Canada, said: “It appears that aromatase inhibitors have a significant increase in cardiotoxic side effects, such as heart attack, angina and heart failure.

“However, it appears from the data — and this is strictly hypothesis-generating — that if a woman switches from one drug to another, there is a reduction in the risk from death from causes other than breast cancer,” Amir added.

“This potentially suggests that there may be side effects that build up the longer a woman is on a certain drug, but switching drugs may reduce the side effects.”

Ben Adams