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Odkazy a zdroje - Studie - 4S



4S

Scandinavian Simvastatin Survival Study

Author(s)
(a), (b) and (d) The Scandinavian Simvastatin Survival Study group
(c) Kjekshus J, Pedersen TR
(e) Pedersen TR, Berg K, Cook TJ, Fargeman O, Haghfelt T, Kjekshus J, Miettinen T, Musliner TA, Olsson AG, Pyörälä K, Thorgeirsson G, Tobert JA, Wedel H, Wilhelmsen L
(f) Reckless JPD
(g) Jönsson B, Johannesson M, Kjekshus J, Olsson AG, Pedersen TR, Wedel H

Title(s)
(a) Design and baseline results of the Scandinavian Simvastatin Survival Study of patients with stable angina and/or previous myocardial infarction
(b) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
(c) Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin Survival Study (4S)
(d) Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survival Study (4S)
(e) Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study
(f) The 4S study and its pharmacoeconomic implications
(g) Cost-effectiveness of cholesterol lowering. Results from the Scandinavian Simvastatin Survival Study (4S)

Reference(s)
(a) Am J Cardiol 1993;71:393-400
(b) Lancet 1994;344:1383-9
(c) Am J Cardiol 1995;76:64C-8C
(d) Lancet 1995;345:1274-5
(e) Arch Intern Med 1996;156:2085-92
(f) PharmacoEconomics 1996;9:101-5
(g) Eur Heart J 1996;17:1001-7

Disease
Coronary artery disease and mild or moderate hypercholesterolaemia

Purpose
To investigate whether long-term treatment with simvastatin in patients with serum total cholesterol levels between 5.5 and 8.0 mmol/l will reduce overall mortality. Secondary, whether the incidence of major coronary artery disease events is reduced by simvastatin

Study design
Randomised, double-blind, placebo-controlled

Follow-up
Minimum 3 years, median 5.4 years

Patients
4444 men and women, aged 35-69 years, with coronary artery disease and serum total cholesterol between 5.5 and 8.0 mmol/l after 8 weeks of dietary treatment

Treatment regimen
Simvastatin, 20 mg once daily, or placebo. If serum cholesterol > 5.2 mmol/l at 6 or 18 weeks of therapy, simvastatin, 40 mg once daily, or placebo

Concomitant therapy
Dietary advice 8 weeks prior to randomisation

Results
Over a median of 5.4 years of follow-up, simvastatin produced mean changes in total cholesterol, LDL cholesterol, and HDL cholesterol of -25%, -35%, and +8%, respectively. In the placebo group 12% of patients died, in the simvastatin group 8%, a risk reduction of 30% (p = 0.0003) attributable to a 42% decrease in the risk of coronary death. 28% of patients in the placebo group and 19% in the simvastatin group had one or more major coronary events (risk reduction 34%; p < 0.00001). Active treatment lead to a 37% reduction in the risk of undergoing myocardial revascularisation procedures (p < 0.00001). A significant reduction in major coronary events was noted in 202 diabetic patients treated with simvastatin compared to placebo (p = 0.002), and in women and patients of both sexes ? 60 years. The relative risk reduction for major coronary events in the simvastatin group was 35% in the lowest quartile of baseline LDL cholesterol and 36% in the highest. Simvastatin significantly reduced the risk of major coronary events in all quartiles of baseline total, HDL and LDL cholesterol, by a similar amount in each quartile. The only clearly drug-related serious adverse event was a single reversible case of myopathy. Simvastatin use was associated with a 32% reduction in the total cost of hospitalisation compared to the use of placebo. The cost of simvastatin therapy per discounted life-year saved was £5502