| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1995;91:2274-2282.)
© 1995 American Heart Association, Inc.
Articles |
Cholesterol Reduction Yields Clinical Benefit
A New Look at Old Data
From Merck Research Laboratories, West Point, Pa (A.L.G., N.C.S.,
J.F.H.); the National Institutes of Health, Bethesda, Md
1
(J.E.R.); and Bowman Gray School of Medicine, Winston-Salem, NC
(C.D.F.).
Background There has been a continuing debate about the overall benefit of cholesterol lowering. We performed a novel meta-analysis of all randomized trials of more than 2 years' duration (n=35 trials) to describe how coronary-heart-disease (CHD), non-CHD, and total mortality are related to cholesterol lowering and to type of intervention.
Methods and Results The analytic approach was designed to separate the effects of cholesterol lowering itself from the other effects of the different types of intervention used. For every 10 percentage points of cholesterol lowering, CHD mortality was reduced by 13% (P<.002) and total mortality by 10% (P<.03). Cholesterol lowering had no effect on non-CHD mortality. Certain types of intervention had specific effects independent of cholesterol lowering. Fibrates (clofibrates, 7 trials; gemfibrozil, 2 trials) increased non-CHD mortality by about 30% (P<.01) and total mortality by about 17% (P<.02). Hormones (estrogen, 2 trials; dextrothyroxin, 2 trials) increased CHD mortality in men by about 27% (P<.04), non-CHD mortality by about 55% (P<.03), and total mortality by about 33% (P<.01). No specific effects independent of cholesterol lowering were found due to diet (n=11) or other interventions (resins, 5; niacin, 3; statins, 2; partial ileal bypass, 1).
Conclusions The results suggest that cholesterol lowering itself is beneficial but that specific adverse effects of fibrates and hormones increase the risk of CHD (hormones only), non-CHD, and total mortality.
Key Words: cholesterol • meta-analysis • mortality
This article has been cited by other articles:
 |
|
 |
|
  A. Sampayo-Reyes, A. Narro-Juarez, S. Said-Fernandez, H. G. Lozano-Garza, J. Vargas-Villarreal, B. D. Mata-Cardenas, A. Morales-Aguilera, M. T. Gonzalez-Garza, E. I. Cortes-Gutierrez, R. M. Cerda-Flores, et al. Effect of Clofibric Acid on Desmin and Vimentin Contents in Rat Myocardiocytes International Journal of Toxicology, September 1, 2006; 25(5): 403 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Prepared by: British Cardiac Society, British Hype JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice Heart, December 1, 2005; 91(suppl_5): v1 - v52. [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Legro, E. Myers, and for the Reproductive Medicine Network Surrogate end-points or primary outcomes in clinical trials in women with polycystic ovary syndrome? Hum. Reprod., August 1, 2004; 19(8): 1697 - 1704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P.J. Halcox and J. E. Deanfield Beyond the Laboratory: Clinical Implications for Statin Pleiotropy Circulation, June 1, 2004; 109(21_suppl_1): II-42 - II-48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Kelloff, J. A. O'Shaughnessy, G. B. Gordon, E. T. Hawk, and C. C. Sigman Counterpoint: Because Some Surrogate End Point Biomarkers Measure the Neoplastic Process They Will Have High Utility in the Development of Cancer Chemopreventive Agents against Sporadic Cancers Cancer Epidemiol. Biomarkers Prev., July 1, 2003; 12(7): 593 - 596. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Decensi, C. Robertson, G. Viale, F. Pigatto, H. Johansson, E. R. Kisanga, P. Veronesi, R. Torrisi, M. Cazzaniga, S. Mora, et al. A Randomized Trial of Low-Dose Tamoxifen on Breast Cancer Proliferation and Blood Estrogenic Biomarkers J Natl Cancer Inst, June 4, 2003; 95(11): 779 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Llewellyn-Thomas, J. M. Paterson, J. A. Carter, A. Basinski, M. G. Myers, G. D. Hardacre, E. V. Dunn, R. B. D'Agostino, P. A. Wolf, and C. D. Naylor Primary Prevention Drug Therapy: Can It Meet Patients' Requirements for Reduced Risk? Med Decis Making, August 1, 2002; 22(4): 326 - 339. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Yarzebski, C. F. Bujor, R. J. Goldberg, F. Spencer, D. Lessard, and J. M. Gore A Community-Wide Survey of Physician Practices and Attitudes Toward Cholesterol Management in Patients With Recent Acute Myocardial Infarction Arch Intern Med, April 8, 2002; 162(7): 797 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Lichtenstein, L. M. Ausman, S. M. Jalbert, M. Vilella-Bach, M. Jauhiainen, S. McGladdery, A. T. Erkkila, C. Ehnholm, J. Frohlich, and E. J. Schaefer Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects J. Lipid Res., February 1, 2002; 43(2): 264 - 273. [Abstract] [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. A. O'Shaughnessy, G. J. Kelloff, G. B. Gordon, A. J. Dannenberg, W. K. Hong, C. J. Fabian, C. C. Sigman, M. M. Bertagnolli, S. P. Stratton, S. Lam, et al. Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development : Recommendations of the American Association for Cancer Research Task Force on the Treatment and Prevention of Intraepithelial Neoplasia Clin. Cancer Res., February 1, 2002; 8(2): 314 - 346. [Abstract] [Full Text] [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]
|
|
|
|
|
|
G. J. Kelloff, C. C. Sigman, K. M. Johnson, C. W. Boone, P. Greenwald, J. A. Crowell, E. T. Hawk, and L. A. Doody Perspectives on Surrogate End Points in the Development of Drugs that Reduce the Risk of Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2000; 9(2): 127 - 137. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Budzynski, J. Rybakowski, M. Swiatkowski, L. Torlinski, M. Klopocka, W. Kosmowski, and M. Ziolkowski NALTREXONE EXERTS A FAVOURABLE EFFECT ON PLASMA LIPIDS IN ABSTINENT PATIENTS WITH ALCOHOL DEPENDENCE Alcohol Alcohol., January 1, 2000; 35(1): 91 - 97. [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]
|
|
|
|
|
|
B. M. Psaty, N. S. Weiss, C. D. Furberg, T. D. Koepsell, D. S. Siscovick, F. R. Rosendaal, N. L. Smith, S. R. Heckbert, R. C. Kaplan, D. Lin, et al. Surrogate End Points, Health Outcomes, and the Drug-Approval Process for the Treatment of Risk Factors for Cardiovascular Disease JAMA, August 25, 1999; 282(8): 786 - 790. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Gotto Jr Lipid-lowering therapy for the primary prevention of coronary heart disease J. Am. Coll. Cardiol., June 1, 1999; 33(7): 2078 - 2082. [Full Text] [PDF]
|
|
|
|
|
|
J. E. Rossouw Does Estrogen Have a Role in the Prevention of Cardiovascular Disease? J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1806 - 1810. [Full Text]
|
|
|
|
|
|
P. B. Gorelick, R. L. Sacco, D. B. Smith, M. Alberts, L. Mustone-Alexander, D. Rader, J. L. Ross, E. Raps, M. N. Ozer, L. M. Brass, et al. Prevention of a First Stroke: A Review of Guidelines and a Multidisciplinary Consensus Statement From the National Stroke Association JAMA, March 24, 1999; 281(12): 1112 - 1120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Brier, J. J. Tornow, A. J. Ries, M. P. Weber, and J. R. Downs Forecasting Patient Outcomes in the Management of Hyperlipidemia Arch Intern Med, March 22, 1999; 159(6): 569 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. Bucher, L. E. Griffith, and G. H. Guyatt Systematic Review on the Risk and Benefit of Different Cholesterol-Lowering Interventions Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 187 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Jacobson, J. R. Schein, A. Williamson, and C. M. Ballantyne Maximizing the Cost-effectiveness of Lipid-Lowering Therapy Arch Intern Med, October 12, 1998; 158(18): 1977 - 1989. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society, and endorsed by the British Diabetic Association Joint British recommendations on prevention of coronary heart disease in clinical practice Heart, July 1, 1998; 80(90002): 1S - 29. [Full Text]
|
|
|
|
|
|
A. L. Gould, J. E. Rossouw, N. C. Santanello, J. F. Heyse, and C. D. Furberg Cholesterol Reduction Yields Clinical Benefit : Impact of Statin Trials Circulation, March 17, 1998; 97(10): 946 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Perreault, V. H. Hamilton, F. Lavoie, and S. A. Grover Treating Hyperlipidemia for the Primary Prevention of Coronary Disease: Are Higher Dosages of Lovastatin Cost-effective? Arch Intern Med, February 23, 1998; 158(4): 375 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Gotto Jr Cholesterol Management in Theory and Practice Circulation, December 16, 1997; 96(12): 4424 - 4430. [Abstract] [Full Text]
|
|
|
|
|
|
G. Fager and O. Wiklund Cholesterol Reduction and Clinical Benefit : Are There Limits to Our Expectations? Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3527 - 3533. [Abstract] [Full Text]
|
|
|
|
|
|
J. H. Markovitz, D. Smith, J. M. Raczynski, A. Oberman, O. D. Williams, S. Knox, and D. R. Jacobs Jr Lack of Relations of Hostility, Negative Affect, and High-Risk Behavior With Low Plasma Lipid Levels in the Coronary Artery Risk Development in Young Adults Study Arch Intern Med, September 22, 1997; 157(17): 1953 - 1959. [Abstract] [PDF]
|
|
|
|
|
|
A. Fagot-Campagna, R. L. Hanson, K. M. V. Narayan, M. L. Sievers, D. J. Pettitt, R. G. Nelson, and W. C. Knowler Serum Cholesterol and Mortality Rates in a Native American Population With Low Cholesterol Concentrations : A U-Shaped Association Circulation, September 2, 1997; 96(5): 1408 - 1415. [Abstract] [Full Text]
|
|
|
|
|
|
P. R. Hebert, J. M. Gaziano, K. S. Chan, and C. H. Hennekens Cholesterol Lowering With Statin Drugs, Risk of Stroke, and Total Mortality: An Overview of Randomized Trials JAMA, July 23, 1997; 278(4): 313 - 321. [Abstract] [PDF]
|
|
|
|
|
|
A. M. Garber and W. S. Browner Cholesterol Screening Guidelines : Consensus, Evidence, and Common Sense Circulation, March 18, 1997; 95(6): 1642 - 1645. [Full Text]
|
|
|
|
|
|
M. H. Moghadasian, B. M. McManus, P. H. Pritchard, and J. J. Frohlich "Tall Oil"–Derived Phytosterols Reduce Atherosclerosis in ApoE-Deficient Mice Arterioscler Thromb Vasc Biol, January 1, 1997; 17(1): 119 - 126. [Abstract] [Full Text]
|
|
|
|
|
|
J. E. Rossouw Estrogens for Prevention of Coronary Heart Disease: Putting the Brakes on the Bandwagon Circulation, December 1, 1996; 94(11): 2982 - 2985. [Full Text]
|
|
|
|
|
|
T. R. Pedersen, K. Berg, T. J. Cook, O. Faergeman, T. Haghfelt, J. Kjekshus, T. Miettinen, T. A. Musliner, A. G. Olsson, K. Pyorala, et al. Safety and Tolerability of Cholesterol Lowering With Simvastatin During 5 Years in the Scandinavian Simvastatin Survival Study Arch Intern Med, October 14, 1996; 156(18): 2085 - 2092. [Abstract] [PDF]
|
|
|
|
|
|
R. Marchioli, R. M. Marfisi, F. Carinci, and G. Tognoni Meta-analysis, Clinical Trials, and Transferability of Research Results Into Practice: The Case of Cholesterol-Lowering Interventions in the Secondary Prevention of Coronary Heart Disease Arch Intern Med, June 10, 1996; 156(11): 1158 - 1172. [Abstract] [PDF]
|
|
|
|
|
|
T. B. Newman and S. B. Hulley Carcinogenicity of Lipid-Lowering Drugs-Reply JAMA, May 15, 1996; 275(19): 1481 - 1482. [Abstract] [PDF]
|
|
|
|
|
|
T. R. Pedersen, J. Kjekshus, K. Berg, A. G. Olsson, L. Wilhelmsen, H. Wedel, K. Pyorala, T. Miettinen, T. Haghfelt, O. Færgeman, et al. Cholesterol Lowering and the Use of Healthcare Resources : Results of the Scandinavian Simvastatin Survival Study Circulation, May 15, 1996; 93(10): 1796 - 1802. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. A. Stein, M. H. Davidson, C. A. Dujovne, D. B. Hunninghake, R. B. Goldberg, D. R. Illingworth, R. H. Knopp, V. T. Miller, P. Frost, J. L. Isaacsohn, et al. Efficacy and Tolerability of Low-dose Simvastatin and Niacin, Alone and in Combination, in Patients With Combined Hyperlipidemia: A Prospective Trial Journal of Cardiovascular Pharmacology and Therapeutics, April 1, 1996; 1(2): 107 - 116. [Abstract] [PDF]
|
|
|
|
|
|
D.R. Illingworth, E.A. Stein, R.H. Knopp, D.B. Hunninghake, M.H. Davidson, C.A. Dujovne, V.T. Miller, J.A. Tobert, P.M. Laskarzewski, J.L. Isaacsohn, et al. A Randomized Multicenter Trial Comparing the Efficacy of Simvastatin and Fluvastatin Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1996; 1(1): 23 - 29. [Abstract] [PDF]
|
|
|
|
 |
|
 T. R. Pedersen Lowering Cholesterol with Drugs and Diet N. Engl. J. Med., November 16, 1995; 333(20): 1350 - 1351. [Full Text]
|
|
|
|
|
|
C. D. Furberg Should Dihydropyridines Be Used as First-Line Drugs in the Treatment of Hypertension? The Con Side Arch Intern Med, November 13, 1995; 155(20): 2157 - 2161. [Abstract] [PDF]
|
|
|
|
|
|
L. H. Opie and F. H. Messerli Nifedipine and Mortality : Grave Defects in the Dossier Circulation, September 1, 1995; 92(5): 1068 - 1073. [Full Text]
|
|
|
|
|
|
M. A. Denke and M. A. Winker Cholesterol and Coronary Heart Disease in Older Adults: No Easy Answers JAMA, August 16, 1995; 274(7): 575 - 577. [Abstract] [PDF]
|
|