Monday, October 15, 2012

Hormone-replacement therapy (HRT) in postmenopausal women with a mean age of 50 significantly reduced the risk of the combined end point of mortality, MI, or heart failure

Hormone-replacement therapy (HRT) in postmenopausal women with a mean age of 50 significantly reduced the risk of the combined end point of mortality, MI, or heart failure in a new randomized Danish study published online October 9, 2012 in BMJ

This is the longest randomized trial with hard end points, there is  a 50% reduction in cardiovascular end points for the women who took HRT, and there was no increased risk of cancer.
The study conclusions are statistically significant and congruent with older observational studies such as the Nurses' Health Study and the subgroup-stratified analyses of the WHI cohort from 50 to 60.
The study also confirms the hypothesis, that the timing of initiating HRT in women in crucial for the patients to derive any benefit. In studies (WHI Study), where women initated HRT at a later stage (average age 63), there was no CV benefit observed

The 1006 healthy women aged 45 to 58 who were recently postmenopausal or had perimenopausal symptoms were participants in the Danish Osteoporosis Prevention Study and were randomized to receive HRT (n=502) or no treatment .

The primary end point was a composite of death, hospitalization for heart failure, and MI. Secondary end points were the individual components of the primary end point and admission to the hospital for stroke. Safety end points included death or a diagnosis of breast cancer or other cancer grouped together and admission to the hospital for pulmonary embolism or deep venous thrombosis (DVT).
The women in the treated group with an intact uterus received 2-mg synthetic 17--estradiol for 12 days, 2 mg 17--estradiol plus 1 mg  norethindrone acetate for 10 days, and 1 mg 17--estradiol for six days (Trisekvens, Novo Nordisk, Denmark). In women who had undergone hysterectomy, first-line treatment was 2 mg 17--estradiol a day (Estrofem, Novo Nordisk, Denmark). Other treatment modalities were offered to those who experienced side effects or insufficient relief of symptoms.
The planned duration of the study was 20 years. However, as the WHI data—which came out in 2002 around the time of the 10-year visit—indicated that use of HRT might result in more harm than benefit, the participants were advised to stop treatment. But they were followed for death, cardiovascular disease, and cancer for up to 16 years.
After 10 years of intervention, there was a 52% reduction in the primary composite end point of death, MI, or heart failure, and this was not associated with an increase in any cancer. Schierbeck said numbers were too small to draw any meaningful conclusions on venous thromboembolism (VTE), although she acknowledges that HRT is known to increase the risk of VTE but pointed out, "This is a less serious event than a CV event."
After 16 years, the reduction in the primary composite outcome was still present and still not associated with an increase in any cancer, something both Schierbeck and Hodis say is "reassuring," particularly in terms of breast cancer.