Hormone therapy had no significant effect on the secondary prevention of coronary heart disease in postmenopausal women
- Shah, Dr Sunil
BACKGROUND
Observational studies have found lower rates of coronary heart disease among women who take post-menopausal estrogen. This association has been reported to be especially strong for secondary prevention.
OBJECTIVE
To determine the efficacy of estrogen plus progestin in the secondary prevention of coronary heart disease in postmenopausal women.
PARTICIPANTS AND SETTING
2763 postmenopausal women younger than 80 years old (mean age 66.7), with established coronary disease and an intact uterus. Twenty clinical centers, USA.
METHOD
Randomized double-blind, placebo-controlled trial with intention to treat analysis.
LITERATURE REVIEW
No explicit strategy; 55 references.
INTERVENTIONS
Conjugated equine estrogens (0.625 mg) plus 2.5 mg of medroxyprogesteron acetate (progestin) in one tablet daily (n = 1380), or placebo of identical appearance (n = 1383).
MAIN OUTCOME MEASURES
Occurrence of non-fatal myocardial infarction or coronary heart disease death. Secondary measures included coronary artery bypass graft surgery, percutaneous coronary revascularization, congestive heart failure, stroke or transient ischemic attack and total mortality.
RESULTS
Average follow-up was 4.1 years. Primary coronary heart disease events occurred in 172 women in the hormone group and 176 women in the placebo group (relative risk 0.99, 95% CI 0.80 to 1.22). These events consisted of coronary heart disease deaths (RR 1.24, 95% CI 0.87 to 1.75) and non-fatal heart attacks (RR 0.91, 95% CI 0.71 to 1.17). There was no significant difference in overall mortality between the two groups. There was a significant increase in venous thrombeoemoblic events in the hormone group (RR 2.89, 95% CI 1.50 to 5.58) and in gallbladder disease (RR 1.38, 95% CI 1.00 to 1.92). The hormone group appeared to have increased risk for primary coronary heart disease in the first year and a decrease in subsequent years. This does not represent a true randomized comparison.
AUTHORS' CONCLUSIONS
The trial found no significant benefit from hormone therapy on coronary heart disease among postmenopausal women with existing disease. This does not exclude a benefit among younger, healthier women, nor benefit from estrogen alone. The time-dependent effect is also plausible, requires longer follow-up and suggests that those already taking hormone therapy for a year or more should not discontinue. Further large randomized controlled trials can investigate these possibilities.