science

Scandinavian Simvastatin Survival Study

Scandinavian Simvastatin Survival Study is a science topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Scandinavian Simvastatin Survival Study rather than just read about it. In short: The Scandinavian Simvastatin Survival Study (also known as the 4S study), was a multicentre, randomized, double-blind, placebo-controlled clinical trial, which provided the initial data that supported the use of the cholesterol-lowering drug, simvastatin, in people with a moderately raised cholesterol and coronary heart disease (CHD); that is people who had previously had a heart attack or angina. The study was spon…

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Reference excerpt

The Scandinavian Simvastatin Survival Study (also known as the 4S study), was a multicentre, randomized, double-blind, placebo-controlled clinical trial, which provided the initial data that supported the use of the cholesterol-lowering drug, simvastatin, in people with a moderately raised cholesterol and coronary heart disease (CHD); that is people who had previously had a heart attack or angina. The study was sponsored by the pharmaceutical company Merck and enrolled 4,444 people from 94 centres in Scandinavia. Before the 4S study, it was not proven that lowering cholesterol could prolong life in people who had CHD. The study concluded that secondary prevention with simvastatin in a high risk group with CHD reduced overall mortality by 30%. Published in The Lancet in 1994, it is considered a "landmark paper".

Objective The 4S multicentre, randomized, double-blind, placebo-controlled clinical trial enrolled 4,444 people chosen from 7,027 people who had been followed up for two months after being given dietary advice. The objective of the study was to assess the effect of a cholesterol-lowering drug called simvastatin on mortality and morbidity in people with a history of a previous heart attack or angina, who also had a moderately raised cholesterol; between 5.5 and 8.0 mmol/L. 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.

Study details The participants, all at high risk of death from CHD and death in general, 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. Of the 4,444 people enrolled in the study, 3,617 were men and 827 women, 2,223 were randomly assigned a placebo and 2,221 were given 20 to 40 mg of simvastatin daily. The plan was to follow the participants for a minimum of three years or until such a time as total mortality reached 440 deaths. In practice, the study carried for a median period of 5.4 years.

Results

After 5.4 years, compared to the group that were given placebo, the simvastatin group demonstrated a 35% reduction in LDL-C and 30% reduction in overall mortality. The risk of hospital-verified non-fatal myocardial infarction reduced by 37% and fatal and non-fatal cerebrovascular events (stroke and TIA) lessened by 28%. 30 people would need to be treated with simvastatin for about five years, to prevent one death; number needed to treat around 30. There were no extra deaths from other non-cardiac causes such as cancer or trauma. The trial also showed benefits in diabetes, women and older people. A follow-up of treatment with simvastatin for up to eight years was published in 2000. Ten years after the start of the 4S trial, a follow-up study published on 28 August 2004 in The 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. The overall mortality also reduced by 15% at the 10 year mark.

Conclusion The study concluded that secondary prevention with 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.

Response Published in The Lancet in 1994, the 4S trial, had an immediate influence on medical opinion, and is considered a "landmark paper". Several other large multicenter clinical trials followed, leading to widespread use of simvastatin. Data from the 4S trial has frequently been used to analyse the cost-effectiveness of simvastatin in secondary prevention.

See also 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

Further reading 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. PMC 2988224. PMID 21067804.

Illustrations

Scandinavian Simvastatin Survival Study illustration

Worked examples

Example 1 — a first encounter with Scandinavian Simvastatin Survival Study

Start with the simplest possible case. Write down what Scandinavian Simvastatin Survival Study claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Scandinavian Simvastatin Survival Study before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Scandinavian Simvastatin Survival Study ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Scandinavian Simvastatin Survival Study

In research: Scandinavian Simvastatin Survival Study appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Scandinavian Simvastatin Survival Study in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Scandinavian Simvastatin Survival Study is common in secondary-school and first-year university syllabi. It links to neighbouring topics Cardiology, Clinical trials related to cardiology, Epidemiological study projects, so understanding it makes those chapters shorter.
In everyday life: Look for Scandinavian Simvastatin Survival Study outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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Frequently asked questions

What is Scandinavian Simvastatin Survival Study in simple terms?

Why does Scandinavian Simvastatin Survival Study matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

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Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Scandinavian Simvastatin Survival Study.