Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris : Findings from the Scandinavian Simvastatin Survival Study (4S)

• Published in: Circulation (New York, N.Y.) Vol. 96; no. 12; pp. 4211 - 4218
• Main Authors: MIETTINEN, T. A, PYÖRÄLÄ, K, OLSSON, A. G, MUSLINER, T. A, COOK, T. J, FAERGEMAN, O, BERG, K, PEDERSEN, T, KJEKSHUS, J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 16-12-1997; American Heart Association, Inc
• Subjects: Adult; Aged; Aging - physiology; Angina Pectoris - drug therapy; Angina Pectoris - mortality; Angina Pectoris - physiopathology; Anticholesteremic Agents - adverse effects; Anticholesteremic Agents - therapeutic use; Biological and medical sciences; Cohort Studies; Female; General and cellular metabolism. Vitamins; Hospitalization; Humans; Lipids - blood; Male; Medical sciences; Middle Aged; Mortality; Myocardial Infarction - drug therapy; Myocardial Infarction - mortality; Myocardial Infarction - physiopathology; Pharmacology. Drug treatments; Simvastatin - adverse effects; Simvastatin - therapeutic use; Survival Analysis; Scandinavia; Europe; Prognosis; Infarct; Hydroxymethylglutaryl-CoA synthase; Sex; Cardiovascular disease; Lipids; Hyperlipoproteinemia; Lyases; Myocardial disease; Oxo-acid-lyases; Female; Dyslipemia; Human; Enzyme; Simvastatin; Enzyme inhibitor; Metabolic diseases; Coronary heart disease; Carbon-carbon lyases; Chemotherapy; Hypercholesterolemia; Treatment; Follow up study; Risk factor; Myocardium; Elderly; Antilipemic agent
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.96.12.4211

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 > or = 65 years of age, those < 65 years of age, women, and men.
The 4S cohort of 4444 CHD patients included 827 women and 1021 patients > or = 65 years of age. Total cholesterol at baseline was 5.5 to 8.0 mmol/L with triglycerides < or = 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 > or = 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.
Cholesterol lowering with simvastatin produced similar reductions in relative risk for major coronary events in women compared with men and in elderly (> or = 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.