Long-term safety of unopposed estrogen used by women surviving myocardial infarction: 14-year follow-up of the ESPRIT randomised controlled trial

Objective: To compare health outcomes during 14-year observational follow-up in women initially randomised to unopposed estrogen or placebo.

Design: At recruitment to the Estrogen for the Prevention of Re-Infarction Trial (ESPRIT) women were assigned to estradiol valerate: 2 mg or placebo treatment for 2 years.

Setting: Women were recruited from 35 hospitals in the northwest of England and Wales in July 1996-February 2000.

Sample: Women aged 50-69 surviving their first myocardial infarction.

Methods: All women were followed by data linkage to UK mortality and cancer records; mean follow-up 14.1 and 12.6 years, respectively. In an intention-to-treat analysis, hazard ratios (HRs) were computed, overall and stratified by age at recruitment.

Outcome measures: Death (all-cause, cardiac disease, stroke or cancer) and cancer incidence (any, breast or endometrium).

Results: There were 418 deaths in 1017 women randomised. The all-cause mortality HR of 1.07 (95% CI 0.88-1.29) indicated no significant difference between treatment groups. Women aged 50-59 years at recruitment had lower HRs than women aged 60-69 years for all outcomes except ischaemic heart disease. Among 149 incident cancers there were seven cases of breast cancer in the intervention arm and 15 in the placebo; HR 0.47 (95% CI 0.19-1.15). There were no deaths from endometrial cancer but three incident cases, one in the active arm and two in placebo.

Conclusions: These results suggest that unopposed estrogen may be used safely by women with an intact uterus surviving a first myocardial infarction.