(Circulation. 1997;96:4211-4218.)
© 1997 American Heart Association, Inc.
Articles |
Cholesterol-Lowering Therapy in Women and Elderly Patients With Myocardial Infarction or Angina Pectoris
Findings From the Scandinavian Simvastatin Survival Study (4S)
From the Department of Medicine, University of Helsinki (Finland) (T.A.M.); Department of Medicine, University of Kuopio (Finland) (K.P.); Department of Internal Medicine, Linköping (Sweden) University Hospital (A.G.O.); Merck Research Laboratories, Rahway, NJ (T.A.M., T.J.C.); Århus (Denmark) University Hospital (O.F.); Institute of Medical Genetics, University of Oslo (Norway) (K.B.); Medical Department, Åker Hospital, Oslo, Norway (T.P.); and Department of Medicine, Rikshospitalet, Oslo, Norway (J.K.).
Correspondence to Prof Tatu Miettinen, Department of Medicine, University of Helsinki, 00290 Helsinki 29, Finland.
Background The Scandinavian Simvastatin
Survival Study (4S) demonstrated pronounced reductions in mortality and
major coronary events in a cohort of patients with established
coronary heart disease (CHD). The present study provides a
detailed, post hoc assessment of the efficacy and safety of
simvastatin therapy in the following subgroups of 4S
patients: those 
65 years of age, those <65 years of age, women,
and men.
Methods and Results The 4S cohort of 4444 CHD patients included
827 women and 1021 patients 65 years of age. Total
cholesterol at baseline was 5.5 to 8.0 mmol/L with
triglycerides 
2.5 mmol/L. Patients were randomized
to therapy with simvastatin 20 to 40 mg daily or placebo
for a median follow-up period of 5.4 years. End points consisted of
all-cause and CHD mortality, major coronary events (primarily
CHD death and nonfatal myocardial infarction), other acute CHD and
atherosclerotic events, hospitalizations for CHD and
cardiovascular events, and coronary
revascularization procedures. Mean changes in serum
lipids were similar in the different subgroups. In patients 65 years
of age in the simvastatin group, relative risks (95%
confidence intervals) for clinical events were as follows: all-cause
mortality, 0.66 (0.48 to 0.90); CHD mortality, 0.57 (0.39 to 0.83);
major coronary events, 0.66 (0.52 to 0.84); any
atherosclerosis-related event, 0.67 (0.56 to 0.81); and
revascularization procedures, 0.59 (0.41 to 0.84).
In women, the corresponding figures were 1.16 (0.68 to 1.99); 0.86
(0.42 to 1.74), 0.66 (0.48 to 0.91), 0.71 (0.56 to 0.91), and 0.51
(0.30 to 0.86), respectively.
Conclusions Cholesterol lowering with
simvastatin produced similar reductions in relative risk
for major coronary events in women compared with men and in
elderly (65 years of age) compared with younger patients. There were
too few female deaths to assess the effects on mortality in women.
Because mortality rates increased substantially with age, the absolute
risk reduction for both all-cause and CHD mortality in
simvastatin-treated subjects was approximately twice as
great in the older patients.
Key Words: hypercholesterolemia • coronary disease • simvastatin • mortality
This article has been cited by other articles:
 |
|
 |
|
  N K Wenger, S J Lewis, F K Welty, D M Herrington, V Bittner, and on behalf of the TNT Steering Committee and Invest Beneficial effects of aggressive low-density lipoprotein cholesterol lowering in women with stable coronary heart disease in the Treating to New Targets (TNT) study Heart, April 1, 2008; 94(4): 434 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Afilalo, G. Duque, R. Steele, J. W. Jukema, A. J.M. de Craen, and M. J. Eisenberg Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis. J. Am. Coll. Cardiol., January 1, 2008; 51(1): 37 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. P. Roberts, E. Guallar, and A. Rodriguez Efficacy and Safety of Statin Monotherapy in Older Adults: A Meta-Analysis J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2007; 62(8): 879 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Wenger, S. J. Lewis, D. M. Herrington, V. Bittner, F. K. Welty, and for the Treating to New Targets Study Steering Com Outcomes of Using High- or Low-Dose Atorvastatin in Patients 65 Years of Age or Older with Stable Coronary Heart Disease Ann Intern Med, July 3, 2007; 147(1): 1 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. P. Alexander, L. K. Newby, P. W. Armstrong, C. P. Cannon, W. B. Gibler, M. W. Rich, F. Van de Werf, H. D. White, W. D. Weaver, M. D. Naylor, et al. Acute Coronary Care in the Elderly, Part II: ST-Segment-Elevation Myocardial Infarction: A Scientific Statement for Healthcare Professionals From the American Heart Association Council on Clinical Cardiology: In Collaboration With the Society of Geriatric Cardiology Circulation, May 15, 2007; 115(19): 2570 - 2589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Selvin, J. Coresh, and F. L. Brancati The burden and treatment of diabetes in elderly individuals in the u.s. Diabetes Care, November 1, 2006; 29(11): 2415 - 2419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Ray, R. G. Bach, C. P. Cannon, R. Cairns, A. J. Kirtane, S. D. Wiviott, C. H. McCabe, E. Braunwald, C. M. Gibson, and for the PROVE IT-TIMI 22 Investigators Benefits of achieving the NCEP optional LDL-C goal among elderly patients with ACS Eur. Heart J., October 1, 2006; 27(19): 2310 - 2316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Aronow Should the NCEP III Guidelines Be Changed in Elderly and Younger Persons at High Risk for Cardiovascular Events? J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2005; 60(5): 591 - 592. [Full Text] [PDF]
|
|
|
|
|
|
V. A. Hirth Hyperlipidemia in Seniors: Too Much, Too Little, Too Late? J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2005; 60(5): 595 - 597. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhou, E. Rahme, M. Abrahamowicz, J. V. Tu, M. J. Eisenberg, K. Humphries, P. C. Austin, and L. Pilote Effectiveness of statins for secondary prevention in elderly patients after acute myocardial infarction: an evaluation of class effect Can. Med. Assoc. J., April 26, 2005; 172(9): 1187 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Meagher Addressing Cardiovascular Disease in Women: Focus on Dyslipidemia J Am Board Fam Med, November 1, 2004; 17(6): 424 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Aronow Management of the Elderly Person After Myocardial Infarction J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2004; 59(11): 1173 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. E. Walsh and M. Pignone Drug Treatment of Hyperlipidemia in Women JAMA, May 12, 2004; 291(18): 2243 - 2252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O Faergeman Evolution of statin therapy: an ongoing story Eur. Heart J. Suppl., March 1, 2004; 6(suppl_A): A3 - A7. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A Dornbrook-Lavender, M. T Roth, and J. A Pieper Secondary Prevention of Coronary Heart Disease in the Elderly Ann. Pharmacother., December 1, 2003; 37(12): 1867 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kreisberg and A. Oberman Medical Management of Hyperlipidemia/Dyslipidemia J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2445 - 2461. [Full Text] [PDF]
|
|
|
|
|
|
S. Ghosh and W. S. Aronow Utilization of Lipid-Lowering Drugs in Elderly Persons With Increased Serum Low-Density Lipoprotein Cholesterol Associated With Coronary Artery Disease, Symptomatic Peripheral Arterial Disease, Prior Stroke, or Diabetes Mellitus Before and After an Educational Program on Dyslipidemia Treatment J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2003; 58(5): M432 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Safford, L. Eaton, G. Hawley, M. Brimacombe, M. Rajan, H. Li, and L. Pogach Disparities in Use of Lipid-Lowering Medications Among People With Type 2 Diabetes Mellitus Arch Intern Med, April 28, 2003; 163(8): 922 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Kuller Hormone Replacement Therapy and Risk of Cardiovascular Disease: Implications of the Results of the Women's Health Initiative Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 11 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
References Circulation, December 17, 2002; 106(25): 3373 - 3421. [Full Text]
|
|
|
|
|
|
C. A. Allen Maycock, J. B. Muhlestein, B. D. Horne, J. F. Carlquist, T. L. Bair, R. R. Pearson, Q. Li, J. L. Anderson, and Intermountain Heart Collaborative Study Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1777 - 1785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.E. Deanfield The management of special patient populations Eur. Heart J. Suppl., September 1, 2002; 4(suppl_F): F19 - F23. [Abstract] [PDF]
|
|
|
|
|
|
D. O. Fedder, C. E. Koro, G. J. L'Italien, A. M. Gotto Jr, and L. H. Kuller Primary Prevention Lipid-Lowering Drug Therapy * Response Circulation, August 13, 2002; 106 (7): e35 - e36. [Full Text] [PDF]
|
|
|
|
|
|
J. S. Benner, R. J. Glynn, H. Mogun, P. J. Neumann, M. C. Weinstein, and J. Avorn Long-term Persistence in Use of Statin Therapy in Elderly Patients JAMA, July 24, 2002; 288(4): 455 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. B. Applegate Elderly Patients' Adherence to Statin Therapy JAMA, July 24, 2002; 288(4): 495 - 497. [Full Text] [PDF]
|
|
|
|
|
|
W. S. Aronow Guest Editorial: Should Hypercholesterolemia in Older Persons Be Treated to Reduce Cardiovascular Events? J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2002; 57(7): M411 - 413. [Full Text]
|
|
|
|
|
|
D. M. Herrington, E. Vittinghoff, F. Lin, J. Fong, F. Harris, D. Hunninghake, V. Bittner, H. G. Schrott, R. S. Blumenthal, R. Levy, et al. Statin Therapy, Cardiovascular Events, and Total Mortality in the Heart and Estrogen/Progestin Replacement Study (HERS) Circulation, June 25, 2002; 105(25): 2962 - 2967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Lemaitre, B. M. Psaty, S. R. Heckbert, R. A. Kronmal, A. B. Newman, and G. L. Burke Therapy With Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors (Statins) and Associated Risk of Incident Cardiovascular Events in Older Adults: Evidence From the Cardiovascular Health Study Arch Intern Med, June 24, 2002; 162(12): 1395 - 1400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Z. Ayanian, M. B. Landrum, and B. J. McNeil Use of Cholesterol-Lowering Therapy by Elderly Adults After Myocardial Infarction Arch Intern Med, May 13, 2002; 162(9): 1013 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Williams, J. L. Fleg, P. A. Ades, B. R. Chaitman, N. H. Miller, S. M. Mohiuddin, I. S. Ockene, C. B. Taylor, and N. K. Wenger Secondary Prevention of Coronary Heart Disease in the Elderly (With Emphasis on Patients >=75 Years of Age): An American Heart Association Scientific Statement From the Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention Circulation, April 9, 2002; 105(14): 1735 - 1743. [Full Text] [PDF]
|
|
|
|
 |
|
 J. E Roeters van Lennep, H.T. Westerveld, D.W. Erkelens, and E. E van der Wall Risk factors for coronary heart disease: implications of gender Cardiovasc Res, February 15, 2002; 53(3): 538 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Faergeman Estimation and reduction of cardiovascular risk in old people Eur. Heart J., February 2, 2002; 23(4): 261 - 263. [Full Text] [PDF]
|
|
|
|
|
|
R. A. Kreisberg and A. Oberman Lipids and Atherosclerosis: Lessons Learned from Randomized Controlled Trials of Lipid Lowering and Other Relevant Studies J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 423 - 437. [Full Text] [PDF]
|
|
|
|
|
|
J. H. Stein, C. M. Carlsson, K. Papcke-Benson, S. E. Aeschlimann, A. Bodemer, M. Carnes, and P. E. McBride The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1806 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. LaRosa Prevention and Treatment of Coronary Heart Disease: Who Benefits? Circulation, October 2, 2001; 104(14): 1688 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Davidson Treatment of the Elderly with 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors: Focus on Drug Interactions Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2001; 6(3): 219 - 229. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Kagansky, S. Levy, Y. Berner, E. Rimon, and H. Knobler Cholesterol lowering in the older population: time for reassessment? QJM, September 1, 2001; 94(9): 457 - 463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Aguilar-Salinas, G. Olaiz, V. Valles, J. M. R. Torres, F. J. G. Perez, J. A. Rull, R. Rojas, A. Franco, and J. Sepulveda High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey J. Lipid Res., August 1, 2001; 42(8): 1298 - 1307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L Wilhelmsen, K Pyorala, H Wedel, T Cook, T Pedersen, J Kjekshus, and for the 4S Study Group Risk factors for a major coronary event after myocardial infarction in the Scandinavian Simvastatin Survival Study (4S). Impact of predicted risk on the benefit of cholesterol-lowering treatment Eur. Heart J., July 1, 2001; 22(13): 1119 - 1127. [Abstract] [PDF]
|
|
|
|
|
|
J. Yarzebski, F. Spencer, R. J. Goldberg, D. Lessard, and J. M. Gore Temporal Trends (1986-1997) in Cholesterol Level Assessment and Management Practices in Patients With Acute Myocardial Infarction: A Population-Based Perspective Arch Intern Med, June 25, 2001; 161(12): 1521 - 1528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hunt, P. Young, J. Simes, W. Hague, S. Mann, D. Owensby, G. Lane, A. Tonkin, and for the LIPID Investigators Benefits of Pravastatin on Cardiovascular Events and Mortality in Older Patients with Coronary Heart Disease Are Equal to or Exceed Those Seen in Younger Patients: Results from the LIPID Trial Ann Intern Med, May 15, 2001; 134(10): 931 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Aronow Treatment of Older Persons With Hypercholesterolemia With and Without Cardiovascular Disease J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2001; 56(3): 138M - 145. [Abstract] [Full Text]
|
|
|
|
|
|
F. K. Welty Cardiovascular Disease and Dyslipidemia in Women Arch Intern Med, February 26, 2001; 161(4): 514 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Sacks, A. M. Tonkin, J. Shepherd, E. Braunwald, S. Cobbe, C. M. Hawkins, A. Keech, C. Packard, J. Simes, R. Byington, et al. Effect of Pravastatin on Coronary Disease Events in Subgroups Defined by Coronary Risk Factors : The Prospective Pravastatin Pooling Project Circulation, October 17, 2000; 102(16): 1893 - 1900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.G. Isles and J.R. Paterson Identifying patients at risk for coronary heart disease: implications from trials of lipid-lowering drug therapy QJM, September 1, 2000; 93(9): 567 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Ganz, K. M. Kuntz, G. A. Jacobson, and J. Avorn Cost-Effectiveness of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor Therapy in Older Patients with Myocardial Infarction Ann Intern Med, May 16, 2000; 132(10): 780 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Hess, A. M. Demchuk, L. M. Brass, and F. M. Yatsu HMG-CoA reductase inhibitors (statins): A promising approach to stroke prevention Neurology, February 22, 2000; 54(4): 790 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. LaRosa, J. He, and S. Vupputuri Effect of Statins on Risk of Coronary Disease: A Meta-analysis of Randomized Controlled Trials JAMA, December 22, 1999; 282(24): 2340 - 2346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Ansell, K. E. Watson, and A. M. Fogelman An Evidence-Based Assessment of the NCEP Adult Treatment Panel II Guidelines JAMA, December 1, 1999; 282(21): 2051 - 2057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Altkorn, K. Roach, S. Stern, and W. Levinson Update in General Internal Medicine Ann Intern Med, August 3, 1999; 131(3): 199 - 206. [Full Text] [PDF]
|
|
|
|
|
|
M. R. Wise, D. E. Stewart, P. Liu, and B. L. Abramson Use of hormone replacement therapy among cardiac patients at a Canadian academic centre Can. Med. Assoc. J., July 1, 1999; 161(1): 33 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Campeau, D. B. Hunninghake, G. L. Knatterud, C. W. White, M. Domanski, S. A. Forman, J. S. Forrester, N. L. Geller, F. L. Gobel, J. A. Herd, et al. Aggressive Cholesterol Lowering Delays Saphenous Vein Graft Atherosclerosis in Women, the Elderly, and Patients With Associated Risk Factors : NHLBI Post Coronary Artery Bypass Graft Clinical Trial Circulation, June 29, 1999; 99(25): 3241 - 3247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Barrett-Connor and C. Stuenkel Hormones and Heart Disease in Women: Heart and Estrogen/Progestin Replacement Study in Perspective J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1848 - 1853. [Full Text]
|
|
|
|
|
|
R. N. Lemaitre, C. D. Furberg, A. B. Newman, S. B. Hulley, D. J. Gordon, J. S. Gottdiener, R. H. McDonald Jr, and B. M. Psaty Time Trends in the Use of Cholesterol-Lowering Agents in Older Adults: The Cardiovascular Health Study Arch Intern Med, September 14, 1998; 158(16): 1761 - 1768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Lewis, F. M. Sacks, J. S. Mitchell, C. East, S. Glasser, S. Kell, R. Letterer, M. Limacher, L. A. Moye, J. L. Rouleau, et al. Effect of pravastatin on cardiovascular events in women after myocardial infarction: the Cholesterol and Recurrent Events (CARE) trial J. Am. Coll. Cardiol., July 1, 1998; 32(1): 140 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Benefits of Lipid Lowering Extend to Women with Established CHD Journal Watch Women's Health, February 1, 1998; 1998(201): 14 - 14. [Full Text]
|
|
|
|
 |
|
 Benefits of Lipid-Lowering Extend to Women with CHD Journal Watch Cardiology, January 9, 1998; 1998(109): 5 - 5. [Full Text]
|
|
|
|
 |
|
 CHOLESTEROL REDUCTION AFTER MI BENEFITS ELDERLY OF BOTH SEXES Journal Watch (General), January |