Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II).
BACKGROUND
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.


METHODS
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.


METHODS
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.


METHODS
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.


METHODS
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 disease.


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.
Grady
Deborah
D
Department of Epidemiology and Biostatistics, University of California, San Francisco, 74 New Montgomery St, Suite 600, San Francisco, CA 94105, USA. dgrady@itsa.ucsf.edu
Herrington
David
D
Bittner
Vera
V
Blumenthal
Roger
R
Davidson
Michael
M
Hlatky
Mark
M
Hsia
Judith
J
Hulley
Stephen
S
Herd
Alan
A
Khan
Steven
S
Newby
L Kristin
LK
Waters
David
D
Vittinghoff
Eric
E
Wenger
Nanette
N
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D003327:Coronary Disease / Q000453:epidemiology* / Q000517:prevention & control; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000453:epidemiology; D017698:Postmenopause; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D004966:Estrogens, Conjugated (USP); D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017258:Medroxyprogesterone Acetate; D001241:Aspirin