oEStrogen in the Prevention of ReInfarction Trial - ESPRIT HRT


To determine if estrogen therapy is associated with a reduction in the risk for reinfarction or death in postmenopausal women who survived a first myocardial infarction.


Estrogen would reduce the cumulative incidence rate for non-fatal reinfarction or cardiac death by one-third compared with placebo.

Study Design

Study Design:

Patients Screened: 14,773
Patients Enrolled: 1,017
Mean Follow Up: 2 years
Mean Patient Age: age 50–69 years (mean age 62.6)
Female: 100

Patient Populations:

Survived MI and discharged alive from hospital within 31 days of admission


Prior MI; use of HRT or vaginal bleeding in the 12 months before admission; history of breast, ovarian, or endometrial carcinoma; or active thrombophlebitis or a history of deep-vein thrombosis or pulmonary embolism, acute or chronic liver disease, Rotor syndrome, Dubin-Johnson syndrome, or severe renal disease

Primary Endpoints:

Reinfarction or cardiac death; all-cause mortality.

Secondary Endpoints:

Uterine bleeding; endometrial cancer; stroke or other embolic events; and fractures.

Drug/Procedures Used:

Women were randomized to estradiol valerate (2 mg tablet daily, n=513) or placebo (n=504) for 2 years.

Principal Findings:

Treatment compliance was low in both arms (43% in estrogen arm and 63% in placebo arm at 2 years). Part of the higher rate of noncompliance was attributed to the higher vaginal bleeding rate in non-hysterectomised women in the estradiol arm (56% vs 7%). There was no difference in the frequency of reinfarction or cardiac death between the estrogen and placebo arms at 2 years by intent to treat (12.1% vs 12.1%, RR 0.99, 95% CI 0.70-1.41, p=0.97). All-cause mortality was non-significantly lower in the estrogen arm at 2 years (6.2% vs 7.7%, 0.79, 0.50-1.27, p=0.34). In an as treated analysis, there again was no difference in the rate ratio for reinfarction or cardiac death (RR 1.04, 95% CI 0.72-1.51, p=0.83). There were no differences in the risk ratios for any of the secondary endpoints between the two arms, including stroke (RR 1.64, p=0.45), deep vein thrombosis (RR 1.96, p=1.00), breast cancer (RR 0.98, p=1.00) or fracture (RR 0.60, p=0.19).


Among postmenopausal women who survive a first MI, the ESPRIT trial demonstrates that estrogen therapy is not associated with any improvement in CV endpoints such as cardiac death or reinfarction or all cause mortality. These results are similar to those oberved in the HERS trial, which likewise demonstrated no benefit in coronary events reduction with hormone replacement therapy. Unlike the HERS trial which evaluated combined treatments with estrogen plus progesterone, the present study used unopposed estrogen. In addition to the lack of benefit with estrogen, vaginal bleeding was more frequent in this arm. Given the similar findings in multiple trials, careful consideration to risk and benefit should be used before initiating HRT for secondary prevention of CHD.


Lancet 2002;360:2001–2008.

Clinical Topics: Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism, Nonstatins

Keywords: Progesterone, Odds Ratio, Risk, Myocardial Infarction, Stroke, Contraceptive Agents, Estradiol, Breast Neoplasms, Coronary Disease, Uterine Hemorrhage, Secondary Prevention, Fatty Acids, Omega-3, Estrogens, Venous Thrombosis, Hormone Replacement Therapy, Tablets

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