Context The Heart and Estrogen/progestin Replacement Study (HERS) found no overall
reduction in risk of coronary heart disease (CHD) events among postmenopausal
women with CHD. However, in the hormone group, findings did suggest a higher
risk of CHD events during the first year, and a decreased risk during years
3 to 5.
Objective To determine if the risk reduction observed in the later years of HERS
persisted and resulted in an overall reduced risk of CHD events with additional
years of follow-up.
Design and Setting Randomized, blinded, placebo-controlled trial of 4.1 years' duration
(HERS) and subsequent unblinded follow-up for 2.7 years (HERS II) conducted
at outpatient and community settings at 20 US clinical centers.
Participants A total of 2763 postmenopausal women with CHD and average age of 67
years at enrollment in HERS; 2321 women (93% of those surviving) consented
to follow-up in HERS II.
Intervention Participants were randomly assigned to receive 0.625 mg/d of conjugated
estrogens and 2.5 mg of medroxyprogesterone acetate (n = 1380), or placebo
(n = 1383) during HERS; open-label hormone therapy was prescribed at personal
physicians' discretion during HERS II. The proportions with at least 80% adherence
to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group,
and increased from 0% (year 1) to 8% (year 6) in the placebo group.
Main Outcome Measures The primary outcome was nonfatal myocardial infarction and CHD death.
Secondary cardiovascular events were coronary revascularization, hospitalization
for unstable angina or congestive heart failure, nonfatal ventricular arrhythmia,
sudden death, stroke or transient ischemic attack, and peripheral arterial
Results There were no significant decreases in rates of primary CHD events or
secondary cardiovascular events among women assigned to the hormone group
compared with the placebo group in HERS, HERS II, or overall. The unadjusted
relative hazard (RH) for CHD events in HERS was 0.99 (95% confidence interval
[CI], 0.81-1.22); HERS II, 1.00 (95% CI, 0.77-1.29); and overall, 0.99 (0.84-1.17).
The overall RHs were similar after adjustment for potential confounders and
differential use of statins between treatment groups (RH, 0.97; 95% CI, 0.82-1.14),
and in analyses restricted to women who were adherent to randomized treatment
assignment (RH, 0.96; 95% CI, 0.77-1.19).
Conclusions Lower rates of CHD events among women in the hormone group in the final
years of HERS did not persist during additional years of follow-up. After
6.8 years, hormone therapy did not reduce risk of cardiovascular events in
women with CHD. Postmenopausal hormone therapy should not be used to reduce
risk for CHD events in women with CHD.