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Am Fam Physician. 2002;65(9):1924

Physicians are faced with multiple conflicting studies when dealing with the issue of hormone replacement therapy (HRT) and its impact on cardiovascular disease. Observational studies have shown that HRT in postmenopausal women decreased their risk for cardiovascular deaths. One recent randomized trial in postmenopausal women with known cardiac disease showed no difference between HRT and placebo with regard to cardiac events or mortality at four years. The trial did find that HRT increased the risk for myocardial infarction (MI) during the first year of HRT. Alexander and associates studied the influence of HRT and the subsequent risk of cardiovascular events in women who had a recent MI.

The study consisted of 1,857 women enrolled in the Coumadin Aspirin Reinfarction Study (CARS), who were enrolled within three to 21 days after an MI. HRT consisted of an estrogen-progestin combination or estrogen alone. The patients were divided into previous or current HRT users, new HRT users, and never HRT users. Patients were followed at weeks 1, 2, 3, 4, 6, and 12 following study enrollment, and every three months for the duration of the study.

Primary study end points were reinfarction, nonfatal ischemic stroke, and cardiovascular death. Secondary end points were all-cause mortality, silent MI, unstable angina requiring hospitalization, transient ischemic attack, and systemic embolization. The study also compared the incidence of these end points in women who used an estrogen-progestin combination versus estrogen alone.

Twenty-eight percent (n = 524) of the participants had used HRT at some point. Of these patients, 21 percent (n = 111) were given HRT after their MI. This group of new HRT users had a higher incidence of the primary end points than patients who never used HRT. The main reason for this was the higher rate of unstable angina. Patients who were previous or current users of HRT had no increase in their risk for any of the end points when compared with women who had never used HRT. Patients who used the combination of estrogen and progestin had a lower incidence of the primary end points than users of estrogen only.

The authors conclude that HRT increases the risk for cardiac events after acute MI, primarily because of the increased incidence of unstable angina. The results of this study add to the concerns about the risk of using HRT in patients with known cardiovascular disease. The authors acknowledge that this was a nonrandomized study and, therefore, does not establish a definitive answer about the impact of HRT impact in women with known cardiovascular disease.

editor's note: The issue of the effect of HRT on cardiovascular disease is currently in flux. Some studies have found that HRT had a positive impact on cardiovascular disease; however, these studies were observational and lacked the benefit of being randomized and placebo-controlled. Recent studies have called into question the results of these earlier studies. Alexander and associates found that HRT after acute myocardial infarction increased women's risk for cardiac events; however, this was a nonrandomized trial. Currently, the Women's Health Initiative of the National Heart, Lung, and Blood Institute has an HRT study of more than 27,000 participants. Unfortunately, final results will not be released until 2005. In the meantime, physicians need to understand the risks and benefits of HRT, including results of recent studies that do not support a positive impact on cardiovascular disease. They also must provide their perimenopausal or menopausal patients with this information.—k.e.m.

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