Benefit of aggressive lipid-lowering therapy: insights from the post coronary artery bypass graft study and other trials

  • Carl W White
    Requests for reprints should be addressed to Carl W. White, MD, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Box 508, 420 Delaware Street, S.E., Minneapolis, Minnesota 55455
    Division of Cardiology, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
    Search for articles by this author


      The importance of treating patients to lower cholesterol levels to lessen the risk of developing atherosclerosis is well accepted. However, the benefits of aggressive treatment for lowering low-density lipoprotein (LDL) cholesterol and a defined threshold at which lowering cholesterol is of little use are still questionable. Although definitive answers are still not available, interesting data come from follow-ups and reviews of epidemiologic and clinical trials completed decades ago. In the Seven Countries Study, a 25-year follow-up shows that while absolute levels of coronary artery disease mortality differed by geographic area, the relative increase in mortality due to a given increase in cholesterol was similar in all cultures except Japan. A new look at the Framingham Study reveals that mean serum cholesterol of persons developing coronary disease has been decreasing progressively for the last 3 decades. Most recently, average levels of total serum cholesterol and LDL cholesterol for men are below the levels now recommended for treatment according to the National Cholesterol Education Program guidelines. Clinical and angiographic intervention trials have now ascertained that lowering LDL cholesterol is effective in prevention and in secondary treatment of coronary atherosclerosis. Recent reviews of the Scandinavian Simvastatin Survival Study (4S), the Cholesterol and Recurrent Events (CARE) study, Holme’s meta-analysis of 42 randomized cholesterol-lowering trials, Roussouw’s meta-analysis of 14 angiographic trials, and the Harvard Atherosclerosis Reversibility Project retrospectively validate the effectiveness of treatment and point to those patient populations in which treatment is most effective. The Post Coronary Artery Bypass Graft (Post CABG) trial evaluated aggressive LDL cholesterol-lowering therapy versus moderate treatment goals, and definitively demonstrated that in patients with a moderate increase in serum cholesterol, aggressive lipid lowering compares very positively with a moderate strategy. The benefits of decreasing cholesterol to very low levels are not yet certain, although epidemiologic reviews strongly correlate lower cholesterol levels with lowered coronary artery disease mortality. Meta-analyses confirm that LDL cholesterol lowering is at least as effective in low-risk patients as in those at high risk. Review of the Post CABG trial comes closest to providing practitioners with clinical guidelines.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Verschuren W.M
        • Jacobs D.R
        • Bloemberg B.P.M
        • et al.
        Serum total cholesterol and long-term coronary heart disease mortality in different cultures.
        JAMA. 1995; 274: 131-136
        • Kannel W.B
        Range of serum cholesterol values in the population developing coronary artery disease.
        Am J Cardiol. 1995; 76: 69C-77C
        • Kannel W.B
        • Castelli W.P
        • Gordon T
        Cholesterol in the prediction of atherosclerotic disease.
        Ann Intern Med. 1979; 90: 85-91
        • The Expert Panel
        Report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults.
        Arch Intern Med. 1988; 148: 36-69
        • Ornish D
        • Brown S.E
        • Scherwitz L.W
        • et al.
        Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial.
        Lancet. 1990; 336: 129-153
        • Schuler G
        • Hambrecht R
        • Schlierf G
        • et al.
        Regular physical exercise and low-fat diet.
        Circulation. 1992; 86: 1-11
        • Watts G.F
        • Lewis B
        • Brunt J.N.H
        • et al.
        Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas’ Atherosclerosis Regression Study (STARS).
        Lancet. 1992; 339: 563-569
        • MAAS Investigators
        Effect of simvastatin on coronary atheroma.
        Lancet. 1994; 344: 633-638
        • Brown G
        • Albers J.J
        • Fisher L.D
        • et al.
        Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B.
        N Engl J Med. 1990; 323: 1289-1298
        • Waters D
        • Higginson L
        • Gladstone P
        • et al.
        Effects of monotherapy with an HMG-CoA reductase inhibitor upon the progression of coronary atherosclerosis as assessed by serial quantitative arteriography.
        Circulation. 1994; 89: 959-968
        • Jukema J.W
        • Bruschke A.V.G
        • van Boven A.J
        • et al.
        Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels.
        Circulation. 1995; 91: 2528-2540
        • Scandinavian Simvastatin Survival Study Group
        Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease.
        Lancet. 1994; 344: 1383-1389
        • Scandinavian Simvastatin Survival Study Group
        Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survival Study (4S).
        Lancet. 1995; 345: 1274-1275
        • Sacks F.M
        • Pfeffer M.A
        • Moye L.A
        • et al.
        The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.
        N Engl J Med. 1996; 335: 1001-1009
        • Holme I
        Cholesterol reduction and its impact on coronary artery disease and total mortality.
        Am J Cardiol. 1995; 76: 10C-17C
        • Rossouw J.E
        Lipid-lowering interventions in angiographic trials.
        Am J Cardiol. 1995; 76: 86C-92C
        • Sacks F.M
        • Gibson C.M
        • Rosner B
        • et al.
        The influence of pretreatment low density lipoprotein cholesterol concentrations on the effect of hypocholesterolemic therapy on coronary atherosclerosis in angiographic trials.
        Am J Cardiol. 1995; 76: 78C-85C
        • The Post Coronary Artery Bypass Graft Trial Investigators
        The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts.
        N Engl J Med. 1997; 336: 153-162
        • Rossouw J.E
        • Lewis B
        • Rifkind B.M
        The value of lowering cholesterol after myocardial infarction.
        N Engl J Med. 1990; 323: 1112-1119
        • Rossouw J.E
        • Canner P.L
        • Hulley S.B
        Deaths from injury, violence, and suicide in secondary prevention trials of cholesterol lowering.
        N Engl J Med. 1991; 325 (Letter): 1813