Scandinavian Simvastatin Survival Study
| Scandinavian Simvastatin Survival Study | |
|---|---|
 Simvastatin 3D | |
| Type of project | Multicenter clinical trial |
| Country | Scandinavian countries |
| Established | 1990s |
| Disestablished | 1990s |
| Funding | Merck |
| Status | Completed |
TheScandinavian Simvastatin Survival Study(also known as the4Sstudy), was a multicentre,randomized, double-blind,placebo-controlled clinical trial,which provided the initial data that supported the use of thecholesterol-lowering drug,simvastatin,in people with a moderately raisedcholesterolandcoronary heart disease(CHD); that is people who had previously had aheart attackorangina.The study was sponsored by the pharmaceutical companyMerckand enrolled 4,444 people from 94 centres inScandinavia.[1][2]
Before the 4S study, it was not proven that lowering cholesterol could prolong life in people who had CHD.[3]The study concluded thatsecondary preventionwith simvastatin in a high risk group with CHD reduced overall mortality by 30%.[3]Published inThe Lancetin 1994, it is considered a "landmark paper".[3][4]
Objective
[edit]The 4S multicentre,randomized, double-blind,placebo-controlled clinical trialenrolled 4,444 people chosen from 7,027 people who had been followed up for two months after being given dietary advice.[2]The objective of the study was to assess the effect of acholesterol-lowering drugcalledsimvastatinonmortalityand morbidity in people with a history of a previousheart attackorangina,who also had a moderatelyraised cholesterol;between 5.5 and 8.0 mmol/L.[1][5][6]
A second objective was to investigate whether the incidence of major coronary artery disease events (fatal and nonfatal myocardial infarction and sudden death) could be reduced with simvastatin.[2]
Study details
[edit]The participants, all at high risk of death from CHD and death in general,[5]were selected from 94 clinical centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 1989, and were aged between 35 and 70 years, with the average age being 59.[2][7]Of the 4,444 people enrolled in the study, 3,617 were men and 827 women,[5]2,223 were randomly assigned aplaceboand 2,221 were given 20 to 40 mg of simvastatin daily.[1]The plan was to follow the participants for a minimum of three years or until such a time as total mortality reached 440 deaths.[2][5]In practice, the study carried for a median period of 5.4 years.[3]
Results
[edit]
After 5.4 years, compared to the group that were given placebo, the simvastatin group demonstrated a 35% reduction inLDL-Cand 30% reduction in overall mortality.[1][3]The risk of hospital-verified non-fatal myocardial infarction reduced by 37% and fatal and non-fatalcerebrovascular events(strokeandTIA) lessened by 28%.[1]30 people would need to be treated with simvastatin for about five years, to prevent one death;number needed to treataround 30.[3]There were no extra deaths from other non-cardiac causes such ascanceror trauma.[3][9]The trial also showed benefits in diabetes, women and older people.[3]
A follow-up of treatment with simvastatin for up to eight years was published in 2000.[7]Ten years after the start of the 4S trial, a follow-up study published on 28 August 2004 inThe Lancet,revealed that of those 2,221 people who continued to take simvastatin, there was a further reduction in number of deaths from CHD when compared to those who had switched from placebo to statin at the five year mark.[7][10]The overall mortality also reduced by 15% at the 10 year mark.[3][7]
Conclusion
[edit]The study concluded thatsecondary preventionwith simvastatin in a high risk group with CHD reduced overall mortality by 30%. Non-fatal CHD events and fatal and non-fatal cerebrovascular events were reduced without an increase in risk of cancer.[3]
Response
[edit]Published inThe Lancetin 1994, the 4S trial, had an immediate influence on medical opinion,[9]and is considered a "landmark paper".[3][4][11]Several other large multicenter clinical trials followed, leading to widespread use of simvastatin.[3]
Data from the 4S trial has frequently been used to analyse the cost-effectiveness of simvastatin in secondary prevention.[12][13]
See also
[edit]- Heart Protection Study
- HDL-Atherosclerosis Treatment Study
- West of Scotland Coronary Prevention Study
- Pravastatin or atorvastatin evaluation and infection therapy - thrombolysis in myocardial infarction 22
References
[edit]- ^abcdeFrishman, William H.; Cheng-Lai, Angela; Nawarskas, James (2005)."11. Lipd-lowering drugs".Current Cardiovascular Drugs.Springer Science & Business Media. p. 307.ISBN1-57340-221-4.
- ^abcde"Design and baseline results of the Scandinavian Simvastatin Survival Study of patients with stable angina and/or previous myocardial infarction".The American Journal of Cardiology.71(5): 393–400. 15 February 1993.doi:10.1016/0002-9149(93)90438-i.ISSN0002-9149.PMID8430625.
- ^abcdefghijklMyat, Aung; Gershlick, A. H.; Gershlick, Tony (2012).Landmark Papers in Cardiovascular Medicine.Oxford University Press.p. 31.ISBN978-0-19-959476-4.
- ^abReynolds, L. A.;Tansey, E. M.,eds. (2006).Cholesterol, atherosclerosis and coronary disease in the UK, 1950–2000; Wellcome Witnesses to Twentieth Century Medicine(PDF).Vol. 27. London: Wellcome Trust Centre for the History of Medicine at UCL.ISBN978-085484-107-3.
- ^abcdThompson, Andrew; Shergill, Iqbal S.; Temple, N. (2011).Ethics, Medical Research, and Medicine: Commercialism versus Environmentalism and Social Justice.Springer Science & Business Media.ISBN978-94-010-0794-8.
- ^abcdPedersen, Terje R.; Wilhelmsen, Lars; Færgeman, Ole; Strandberg, Timo E.; Thorgeirsson, Gudmundur; Troedsson, Linda; Kristianson, Johan; Berg, Kåre; Cook, Thomas J.; Haghfelt, Torben; Kjekshus, John (1 August 2000)."Follow-up study of patients randomized in the scandinavian simvastatin survival study (4S) of cholesterol lowering".The American Journal of Cardiology.86(3): 257–262.doi:10.1016/S0002-9149(00)00910-3.ISSN0002-9149.PMID10922429.
- ^"Atheroma".Scientific Animations.Retrieved7 April2020.
- ^abThompson, G. R. (1 February 2009)."History of the cholesterol controversy in Britain".QJM: An International Journal of Medicine.102(2): 81–86.doi:10.1093/qjmed/hcn158.ISSN1460-2725.PMID19042967.
- ^Wood, Shelley (27 August 2004)."Ten-year outcomes from 4S study".Medscape.Retrieved2 April2020.
- ^Jameson, J. Larry; Groot, Leslie J. De (2015).Endocrinology: Adult and Pediatric.Elsevier Health Sciences.p. 730.ISBN978-0-323-32195-2.
- ^Topol, Eric J.; Califf, Robert M. (2007).Textbook of Cardiovascular Medicine.Lippincott Williams & Wilkins. p. 752.ISBN978-0-7817-7012-5.
- ^Jönsson, B.; Johannesson, M.; Kjekshus, J.; Olsson, A. G.; Pedersen, T. R.; Wedel, H. (July 1996)."Cost-effectiveness of cholesterol lowering. Results from the Scandinavian Simvastatin Survival Study (4S)".European Heart Journal.17(7): 1001–1007.doi:10.1093/oxfordjournals.eurheartj.a014994.ISSN0195-668X.PMID8809516.
Further reading
[edit]- Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R (2010)."Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials".Lancet.376(9753): 1670–81.doi:10.1016/S0140-6736(10)61350-5.PMC2988224.PMID21067804.