Published Online
on June 3, 2002

A more recent version of this article appeared on June 25, 2002

This Article Full Text (PDF) All Versions of this Article: 105/25/2962    most recent 01.CIR.0000019406.74017.B2v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Herrington, D. M. Search for Related Content PubMed Articles by Herrington, D. M. Related Collections Acute myocardial infarction Epidemiology

Submitted on January 8, 2002
Revised on April 12, 2002
Accepted on April 12, 2002

Statin Therapy, Cardiovascular Events, and Total Mortality in the Heart and Estrogen/Progestin Replacement Study (HERS)

David M. Herrington MD, MHS^*, Eric Vittinghoff PhD, Feng Lin MS, Josephine Fong MS, Fran Harris MS, Donald Hunninghake MD, Vera Bittner MD, Helmut G. Schrott MD, Roger S. Blumenthal MD, Robert Levy MD, and for the HERS Study Group

From the Department of Internal Medicine/Cardiology (D.M.H.), Wake Forest University School of Medicine, Winston-Salem, NC; the Department of Epidemiology and Biostatistics (E.V., F.L., J.F., F.H.), University of California-San Francisco, San Francisco; the Departments of Pharmacology and Medicine/Cardiology (D.H.), University of Minnesota Health Center, Minneapolis; the Department of Medicine (V.B.), University of Alabama at Birmingham, Birmingham; the Department of Preventive Medicine (H.G.S.), University of Iowa College of Medicine, Iowa City; the Preventive Cardiology Center (R.S.B.), Johns Hopkins Hospital, Baltimore, Md; and Wyeth-Ayerst Research (R.L.), Radnor, Pa.

^* To whom correspondence should be addressed. E-mail: dherring{at}wfubmc.edu.

Background—Although effects of statins on cardiovascular outcomes are well established in men, fewer data exist for women. Furthermore, the effects of statins plus hormone replacement therapy (HRT) on cardiovascular outcomes are uncertain.

Methods and Results—We examined statin use, cardiovascular events, and total mortality in the Heart and Estrogen/progestin Replacement Study (HERS), a randomized clinical trial of estrogen plus progestin versus placebo in postmenopausal women with heart disease (n=2763). A nonrandomized comparison of statin users and nonusers revealed lower rates of the primary outcome, nonfatal myocardial infarction or coronary heart disease death (relative hazard [RH]=0.79, 95% confidence intervals [CI] 0.63 to 0.99, P=0.04), and total mortality (RH=0.67, 95% CI 0.51 to 0.87, P=0.003). Rates of venous thromboembolic events were also lower among statin users (RH=0.45, 95% CI 0.23 to 0.88, P=0.02). HRT resulted in a significant increase in early risk for primary events in women who did not use statins (RH=1.75, 95% CI 1.02 to 3.03, P=0.04) but not in statin users (RH=1.34, 95% CI 0.63 to 2.86, P=0.45). Adjustment for postrandomization statin use showed no effect of HRT on risk for the primary outcome (RH=0.96, 95% CI 0.77 to 1.29; P=0.72).

Conclusions—In HERS, statin use was associated with lower rates of cardiovascular events, venous thromboembolic events, and total mortality. These data provide strong support for statin use in eligible women with coronary disease.

Key words: coronary disease • hormones • lipids • risk factors • women

This article has been cited by other articles:

				J. E Vamvakopoulos, M. Kountouri, T. Marshall, and S. M Greenfield Lifestyle or Life-Saving Medicines? A Primary Healthcare Professional and Consumer Opinion Survey on Over-the-Counter Statins Ann. Pharmacother., March 1, 2008; 42(3): 413 - 420. [Abstract] [Full Text] [PDF]

				C. Mineo, H. Deguchi, J. H. Griffin, and P. W. Shaul Endothelial and Antithrombotic Actions of HDL Circ. Res., June 9, 2006; 98(11): 1352 - 1364. [Abstract] [Full Text] [PDF]

				P. Ouyang, E. D. Michos, and R. H. Karas Hormone Replacement Therapy and the Cardiovascular System: Lessons Learned and Unanswered Questions J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1741 - 1753. [Abstract] [Full Text] [PDF]

				H. Deguchi, N. M. Pecheniuk, D. J. Elias, P. M. Averell, and J. H. Griffin High-Density Lipoprotein Deficiency and Dyslipoproteinemia Associated With Venous Thrombosis in Men Circulation, August 9, 2005; 112(6): 893 - 899. [Abstract] [Full Text] [PDF]

				C H Lee, P de Feyter, P W Serruys, F Saia, P A Lemos, D Goedhart, P R Soares, V A W M Umans, M Ciccone, and M Cortellaro Beneficial effects of fluvastatin following percutaneous coronary intervention in patients with unstable and stable angina: results from the Lescol intervention prevention study (LIPS) Heart, October 1, 2004; 90(10): 1156 - 1161. [Abstract] [Full Text] [PDF]

				S.-H. Juan, J.-J. Chen, C.-H. Chen, H. Lin, C.-F. Cheng, J.-C. Liu, M.-H. Hsieh, Y.-L. Chen, H.-H. Chao, T.-H. Chen, et al. 17{beta}-Estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1254 - H1261. [Abstract] [Full Text] [PDF]

				L. H. Smith, S. R. Coats, H. Qin, M. S. Petrie, J. W. Covington, M. Su, M. Eren, and D. E. Vaughan Differential and Opposing Regulation of PAI-1 Promoter Activity by Estrogen Receptor {alpha} and Estrogen Receptor {beta} in Endothelial Cells Circ. Res., August 6, 2004; 95(3): 269 - 275. [Abstract] [Full Text] [PDF]

				C. Kluft Identifying patients at risk of coronary vascular disease: the potential role of inflammatory markers Eur. Heart J. Suppl., July 1, 2004; 6(suppl_C): C21 - C27. [Abstract] [Full Text] [PDF]

				M. Schillinger, M. Exner, W. Mlekusch, J. Amighi, S. Sabeti, M. Muellner, H. Rumpold, O. Wagner, and E. Minar Statin therapy improves cardiovascular outcome of patients with peripheral artery disease Eur. Heart J., May 1, 2004; 25(9): 742 - 748. [Abstract] [Full Text] [PDF]

				C. D. Bushnell, L. K. Newby, L. B. Goldstein, F. Lin, K. Yaffe, and J. A. Simon Statin use and stroke outcomes in the Heart and Estrogen-Progestin Replacement Study (HERS) Neurology, March 23, 2004; 62(6): 968 - 970. [Abstract] [Full Text] [PDF]

				M. Neves-e-Castro Menopause in crisis post-Women's Health Initiative? A view based on personal clinical experience Hum. Reprod., December 1, 2003; 18(12): 2512 - 2518. [Abstract] [Full Text] [PDF]

				H. N. Hodis, W. J. Mack, S. P. Azen, R. A. Lobo, D. Shoupe, P. R. Mahrer, D. P. Faxon, L. Cashin-Hemphill, M. E. Sanmarco, W. J. French, et al. Hormone Therapy and the Progression of Coronary-Artery Atherosclerosis in Postmenopausal Women N. Engl. J. Med., August 7, 2003; 349(6): 535 - 545. [Abstract] [Full Text] [PDF]

				F. Bilora, V. Boccioletti, F. Petrobelli, and A. Girolami Atherosclerosis and Secondary Deep Vein Thrombosis: A Difficult Correlation Clinical and Applied Thrombosis/Hemostasis, April 1, 2003; 9(2): 121 - 124. [Abstract] [PDF]

				A. P. Miller and S. Oparil Secondary Prevention of Coronary Heart Disease in Women: A Call to Action Ann Intern Med, January 21, 2003; 138(2): 150 - 151. [Full Text] [PDF]

				D. A. Grimes and R. A. Lobo Perspectives on the Women's Health Initiative Trial of Hormone Replacement Therapy Obstet. Gynecol., December 1, 2002; 100(6): 1344 - 1353. [Abstract] [Full Text] [PDF]

				More from HERS: Statins May Blunt Cardiac Risks in Hormone Users Journal Watch Women's Health, August 7, 2002; 2002(807): 3 - 3. [Full Text]