Unresolved issues in early trials of cholesterol lowering

• Published in: The American journal of cardiology Vol. 76; no. 9; pp. 5C - 9C
• Main Author: LaRosa, John C.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 28.09.1995; Elsevier; Elsevier Limited
• Subjects: Aged; Anticholesteremic Agents - therapeutic use; Biological and medical sciences; Cardiovascular disease; Cholesterol; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Clinical Trials as Topic; Coronary Artery Disease - etiology; Coronary Disease - drug therapy; Coronary Disease - etiology; Female; General and cellular metabolism. Vitamins; Humans; Hypercholesterolemia - blood; Hypercholesterolemia - complications; Hypercholesterolemia - drug therapy; Male; Medical research; Medical sciences; Middle Aged; Pharmacology. Drug treatments
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/S0002-9149(99)80464-0

A reexamination of early intervention trials in patients with coronary artery disease (CAD) shows that a pessimistic view of cholesterol reduction in such patients is inappropriate. In observational studies, individuals with documented coronary artery disease and elevated cholesterol levels fare worse than individuals with normal or low cholesterol levels. Early trials of cholesterol reduction in individuals with coronary artery disease succeeded in lowering total cholesterol levels by only 5–15%. Nevertheless, when reviewed in meta-analysis, these trials demonstrated borderline effects on total mortality, statistically significant benefits in terms of morbidity and mortality due to cardiovascular disease and CAD, and no increase in mortality from noncardiovascular causes. Substantially greater lowering of low density lipoprotein (LDL) levels was achieved in early regression studies. In these studies, examples of improvement were noted in individual coronary artery segments. What was not appreciated initially was the dramatic reduction in coronary events. Older secondary prevention trials did not definitively address the benefits of cholesterol reduction in individuals whose cholesterol levels were only modestly elevated (total cholesterol, 160–240 mg/dl [4.14–6.21 mmol/liter], and LDL cholesterol levels 100–160 mg/dl [2.59–4.14 mmol/liter]). Several other issues were not addressed in these early studies, including the effect of declines in triglyceride levels, increases in high density lipoprotein (HDL) levels, and the effects in women and individuals aged >60 years. Even with these limitations, a comparison of meta-analyses of other medical interventions-i.e., β blockade and aspirin therapy-indicates that declines in coronary mortality are in the same range as obtained in older studies with modest cholesterol reduction-i.e., 20–25%. Thus, these early studies provide substantial support for cholesterol reduction in individuals with established CAD.