Circulation. 2000;101:e223-e224
(Circulation. 2000;101:e223.)
© 2000 American Heart Association, Inc.
Circulation Electronic Pages |
Hormone Replacement Therapy and Cardiac Prevention
Beth L. Abramson, MD, FRCPC
Director of Women’s Cardiovascular Health and the
Cardiac Prevention and Rehabilitation Center Assistant
Professor of Medicine,
St. Michael’s Hospital,
University of Toronto,
Toronto, Ontario, Canada
 |
Introduction
|
|---|
To the Editor:
The consensus statement by Mosca et al1 that was recently
published in Circulation should be applauded because it
shows that researchers finally realize that women have unique
cardiovascular needs. Despite this praise, I do have
concerns regarding their overgeneralization of the Heart and
Estrogen/Progestin Replacement Study (HERS) trial2
and their stance on hormone replacement therapy (HRT) for the
prevention of coronary disease. I was disappointed that the
position on HRT was not stronger.
After a critical review of the literature, there are several reasons
why I think this should be the case. First, one must delineate primary
versus secondary prevention when addressing the HRT issue because the
pathophysiology is likely different. In women with established
coronary disease, events occur from antecedent atherosclerotic
plaque rupture and thrombus formation. In those without established
coronary disease, however, the turning point in disease
progression is the development (rather than the rupture, or thrombosis)
of the atherosclerotic plaque. This plaque development is
multifactorial and partially related to endothelial
dysfunction and the establishment of lipids within the
arterial wall. Although the data are nonrandomized, much
exists3 that suggests a benefit of HRT in women without
established coronary disease via a reduction in cardiac events
and death due to coronary heart disease (enough to support a
class B recommendation according to the Canadian Task Force on
Preventative Health Care grading system).
Additionally, one must be cautious when extrapolating results from the
HERS trial to all women with established coronary disease.
Although the authors were correct in stating the cohort was
undertreated with respect to lipid-lowering4 (which is a
major problem in itself in treating female cardiac patients), >80% of
the HERS study group had revascularization within 6
months of entry into the trial. This high rate of
revascularization is likely reflected in the low
event rate in both the placebo and treatment arms of the HERS trial.
The majority of female patients with established coronary
disease (at least in a conservative country such as Canada) are not
treated with revascularization. Unfortunately, the
role of HRT in the female patient will remain contentious. I hope that
doctors do not dismiss the role of HRT in the secondary prevention of
coronary disease. Until further data are available, I think HRT
should be recommended for primary prevention.
|
References
|
|---|
-
Mosca L, Grundy SM, Judelson D, et al.
Guide to preventive cardiology for women.
Circulation.. 1999;99:2480–2484.[Free Full Text]
-
Hulley S, Grady D, Bush TL, et al. Randomized trial of
estrogen plus progestin for secondary prevention of coronary
heart disease in postmenopausal women. JAMA.. 1998;280:605–613.[Abstract/Free Full Text]
-
Stampfer MJ, Colditz GA. Estrogen replacement therapy
and coronary heart disease: a quantitative assessment of the
epidemiologic evidence. Prev Med.. 1991;20:47–63.[Medline]
[Order article via Infotrieve]
-
Schrott HG, Bittner V, Vittinghoff E, et al, for the
HERS research group. Adherence to national cholesterol
education program treatment goals in postmenopausal women with heart
disease: the Heart and Estrogen/Progestin Replacement Study (HERS).
JAMA.. 1997;277:1281–1286.[Abstract]
Response
Lori Mosca, MD, PhD;
Scott M. Grundy, MD, PhD;
Debra Judelson, MD;
Kathleen King, PhD, RN;
Marian Limacher, MD;
Suzanne Oparil, MD;
Richard Pasternak, MD;
Thomas A. Pearson, MD, PhD;
Rita F. Redberg, MD;
Sidney C. Smith, MD;
Mary Winston, EdD, RD;
Stanley Zinberg, MD
Preventative Cardiology Program,
New York Presbyterian Hospital,
622 West 168th Street,
New York, NY 10032
|
Introduction
|
|---|
We agree with Dr Abramson that the results of the Heart and
Estrogen/Progestin
Replacement Study (HERS) should not be
overgeneralized. However,
we do not agree that current data support a
stronger recommendation
for the use of hormone replacement therapy
(HRT) for either
the primary or secondary prevention of
cardiovascular disease
(CVD). We acknowledged in our
consensus statement that the results
of HERS may not apply to women
without vascular disease or who
are on other hormone regimens (such as
progestins other than
medroxyprogesterone acetate or unopposed
estrogen).
R1 Although
the rate of coronary
revascularization is substantially higher
in the
United States compared with Canada, this has not been
associated with
improved 1-year survival.
R2 Moreover, it is
unknown if
revascularization would modify the relation between
HRT
and coronary events.
The potential for HRT to reduce CVD in some women exists; however,
there is also potential for harm. As we pointed out, although there was
an overall null result at the conclusion of the study, there was a
significant increase in CVD events in women treated with combination
HRT in year 1 of HERS. Currently, there are no definitive criteria to
determine which women may be susceptible to early adverse effects
associated with HRT. Therefore, we stated that, at present, the
initiation of HRT in the setting of secondary prevention is not clearly
indicated (but it can be continued if a women has done well with
ongoing therapy).
Although we acknowledge that the pathophysiology of CVD is likely
different in the setting of primary versus secondary prevention, we
submit that this categorization is an oversimplification because many
older women have unrecognized CVD, making the distinction difficult.
The basis for not making a stronger recommendation in primary
prevention is the absence of available data from randomized clinical
trials to test the benefits and risks of HRT in this population. The
role of HRT in primary prevention is supported by observational
epidemiological studies; however, until data from rigorously designed
studies such as the Women’s Health InitiativeR3 and the
European Women’s International Study of Long Duration Oestrogen After
Menopause (WISDOM)R4 are available, we think that it would
be in- appropriate to make a strong recommendation for or against the
use of HRT for primary prevention. In the interim, because HRT has
other benefits and side effects, we think the recommendation to
individualize the decision is justified.
|
References
|
|---|
-
Mosca L, Grundy SM, Judelson D, et al.
AHA/ACC Medical/Scientific Consensus Panel Statement: a guide to
preventive cardiology for women.
Circulation. 1999;99:2480–2484.
-
Tu JV, Pashos CL, Naylor CD, et al. Use of cardiac
procedures and outcomes in elderly patients with myocardial infarction
in the United States and Canada. N Engl J Med. 1997;336:1500–1505.[Abstract/Free Full Text]
-
The Women’s Health Initiative Study Group. Design of
the Women’s Health Initiative clinical trial and observational study.
Control Clin Trials. 1998;19:61–109.[Medline]
[Order article via Infotrieve]
-
Vickers MR, Meade TW, Wilkes HC. Hormone replacement
therapy and cardiovascular disease: the case for a
randomized controlled trial. Ciba Found Symp. 1995;191:150–164.[Medline]
[Order article via Infotrieve]
Top
Introduction
References