Hormone Therapy and In-Hospital Survival after Myocardial Infarction in Postmenopausal Women
February 1, 2002
Hormone Therapy and In-Hospital Survival after Myocardial Infarction in Postmenopausal Women
Abstract & Commentary
The present study was performed with 114,724 women aged 55 years or older with confirmed myocardial infarction (MI) who presented between April 1998 and January 2000 to one of 1674 hospitals participating in the National Registry of Myocardial Infarction-3. At the time of hospitalization, 6.4% of the women reported current use of hormone replacement therapy (HRT). Unadjusted mortality was 7.4% in users of HRT and 16.2% in nonusers. The unadjusted odds ratio was 0.41 with a confidence interval (CI) of 0.36-0.43, indicating that the result reached statistical significance. The women who used HRT differed from the rest of the population in several ways. Hormone users were younger, more likely to be white, less likely to have a history of diabetes or prior MI or stroke, more likely to have hypercholesterolemia and family history of premature coronary artery disease, and more likely to smoke tobacco. The proportion of women who experienced hypotension, ventricular arrhythmia, recurrent MI, stroke, and cardiac rupture with hospitalization was similar among users and nonusers. After adjustment for patient characteristics, use of HRT remained statistically significantly associated with a reduced odds ratio of in-hospital mortality of 0.65 (CI, 0.59-0.72). Shlipak and associates thus concluded that use of HRT at the time of MI was associated with approximately a 35% reduction in mortality (Shlipak MG, et al. Circulation. 2001;104:2300-2304).
Comment by Sarah L. Berga, MD
The present study enrolled women at the time of hospitalization for MI. At the time of enrollment, HRT status was recorded as a yes/no variable. The type or regimen of HRT was not elicited. All that is known is whether a given woman reported taking HRT at the time of their MI. The Heart and Estrogen/Progestin Replacement Study (HERS) trial enrolled women who were not taking HRT at the time of a MI and then randomized them to HRT or placebo. The present study found a significant benefit in terms of survival if one was taking HRT at the time of a MI. The HERS found that women who started HRT after a MI fared less well in the beginning, but better with increasing duration of HRT use. By year 4, the women randomized in the HERS to HRT had a decreased risk of mortality. The variables most likely to explain what might appear to be discrepant results between the HERS and many other observation trials, including the present one, is the duration of HRT use and whether it was begun before the index event. Taken together, these 2 studies raise the question as to how long it takes for HRT to have a beneficial effect. The HERS trial suggested that it takes about 4 or more years for the benefits to clearly outweigh the risks in terms of cardioprotection in women with established cardiovascular disease (CVD).
The editorial that accompanies the present study provides a balanced review about what is known about the mechanisms by which estrogen use might impart cardioprotection.1 Of note, Mendelsohn and Karas highlight the abundant molecular data indicating that estrogen imparts a beneficial effect at the vessel wall.
They make the following points:
- HRT should continue to be used for primary cardioprevention;
- Statins should be used in women with dyslipidemias;
- In selecting the HRT regimen, consideration should be given to the lipid profile because different HRT regimens have different effects on various lipoproteins;
- The first-line therapies for women with known CVD include risk factor modifications, aspirin, beta-blockers, statins, and angiotensin-converting-enzyme inhibitors, just as in men. These therapies are underused, especially in women.
These recommendations make abundant sense. The question that looms is which physician will accept responsibility for implementing them? The choices include cardiologists, internists, family physicians, and gynecologists. There is no doubt in my mind that HRT is best given by gynecologists, if only because we know best how to manage the side effects, especially uterine bleeding. It would be extremely helpful, however, if all physicians sang the same song. Optimally, all would recommend HRT and then defer the administration of HRT to gynecologists with an interest in caring for postmenopausal women. That way, patients would hear a chorus and they would feel less ambivalent about taking HRT. As it is, physicians, especially those in different disciplines, tend to make discordant recommendations. Patients are understandably confused and reluctant. Further, I am hoping that gynecologists can do better in terms of learning to tailor the HRT regimen to the clinical circumstances of the patient. We need to have a firm grounding in the pros and cons of various HRT regimens.
Reference
1. Mendelsohn ME, Karas RH. Circulation. 2001;104: 2256-2259.
Dr. Berga is Professor and Director, Division of Reproductive Endocrinology and Infertility, University of Pittsburgh.
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