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

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.