More Evidence Of Possible Adverse Effects
From New Hormone Use In Women With Heart Disease

Duke University Medical Center

NEW ORLEANS -- Cardiologists should think twice about prescribing hormone replacement therapy for women who have heart disease, researchers at Duke University Medical Center say.

Their study, prepared for the annual meeting of the American College of Cardiology, is the second in a year that finds an association between new use of hormones in women who have previous heart disease and the occurrence of a second cardiac "event," such as a heart attack or unstable angina. This was not seen in women using such hormones before they developed heart disease.

These studies suggest the general message that hormone therapy is good for the hearts of postmenopausal women must be considered further, said Dr. Karen Alexander of the Duke Clinical Research Institute.

"While hormone use has benefits and may still be cardioprotective in women without heart disease, women who have heart disease should probably not start using them," Alexander said. "We also have no reason to suggest women stop using hormones if they develop heart disease." In looking back at a 1996 study of the use of aspirin in heart attack patients, Alexander and her team found that more than 37 percent of women who started using hormone therapy after their attack were hospitalized for unstable angina within almost a year. That rate of hospitalization was significantly higher than for women who had never used hormones (17 percent) and those who had used them before their heart attack (21 percent).

"These data contribute to the evolving understanding of the benefits from hormone use," Alexander said. A study reported last August was the first clue that women with heart disease should not start hormone replacement therapy (HRT), which consists of daily doses of estrogen for women who have had hysterectomies or estrogen plus the progestin hormone for women with an intact uterus.

The August study, led by the University of California at San Francisco and called the Heart and Estrogen/progestin Replacement Study (HERS), found that hormone therapy appeared to increase the risk of a heart attack, especially in the first year of treatment in postmenopausal women with heart disease. It concluded that there was no overall cardiac benefit to hormone use in these women during the four years of the trial, and that the risk of heart attacks seemed to increase soon after starting hormones. The HERS result was unexpected in light of the growing consensus that hormones helped hearts, Alexander said. That conclusion came from numerous "observational" studies which followed the health of women who chose to use estrogen

and/or progestin, compared to women who opted not to use hormones. But women who take HRT also tend to do other things that benefit their health and reduce their risk of heart disease, such as exercising regularly, following a sensible diet and avoiding smoking, Alexander said, so a "natural selection bias" is introduced into such studies which can distort the results. HERS, on the other hand, was a randomized trial of women with heart disease; half of the 2,763 women were assigned to take estrogen and progestin, and the rest were given a placebo -- inactive pills.

After HERS results were released, Alexander looked for Duke studies that had compiled data on how women with heart disease fared on hormone therapy. She came across a treasure trove in a study called CARS (Coumadin Aspirin Reinfarction Study), which compared two different therapies -- aspirin versus aspirin plus coumadin -- in preventing second heart attacks. Coumadin is a anti-coagulant.

While the study ultimately found no difference between the two treatments, it had amassed detailed data on 8,803 patients with heart disease who had suffered a heart attack, including any use of HRT. In this group were 1,857 postmenopausal women. The researchers found:

Of the 111 women who started using hormone therapy after their heart attack, 32.5 percent were hospitalized for unstable angina, which is defined as chest pain that becomes worse or chest pain felt at night. This difference in rates of unstable angina was significantly higher in this group, compared to the other women, and they also had significantly more angioplasty procedures during the study follow-up. No deaths were reported in this group.

Of 413 women who had used hormones before their heart attacks, and who continued to use it during the study, 21 percent were hospitalized for unstable angina and 1 percent died. In the group of 1,333 women who had never used hormones, 17 percent were hospitalized and 4 percent died. The difference in death rates across all groups of women was not significant.

"This was a marvelous opportunity to look at whether the findings from HERS were supported in observational series. We found that new users of HRT had a higher risk of developing unstable angina serious enough to require hospitalization," Alexander said. "I hope there are other studies we can look back on that will help us further our understanding of who best benefits from hormone therapy."

Contact: Renee Twombly 919-684-4148 Duke University Medical Center