PubMed Health⌕ Search

PubMed · 8706591

The 4S study. Implications for prescribing.

Abstract

This article discusses various aspects of cholesterol-lowering therapy using the HMG-CoA reductase inhibitor simvastatin in the light of the large Scandinavian Simvastatin Survival Study (4S). In 4S, patients with proven coronary heart disease (CHD) and plasma total cholesterol > 5.5 mmol/L (212 mg/dl) despite dietary measures received statin therapy or placebo for > or = 5 years. A significant mortality reduction was accomplished in those receiving the statin. Moreover, a significant decrease of nonfatal myocardial infarction and requirement for coronary bypass surgery or angioplasty was demonstrated, which will contribute to the cost-effectiveness of this well tolerated therapy. Plaque stabilisation and improvement of endothelial function are thought to be mediators of this therapeutic success. Responsible drug prescription in the post-4S era may result in the recognition and treatment of more patients with CHD. This is likely to be more beneficial than exhaustive efforts to completely achieve the goals of the most strict guidelines in the individual patient. In patients who carry the highest absolute risk for a recurrent event, aggressive drug therapy may be most justified. Reluctance to initiate lipid lowering drug therapy in patients with proven CHD should now be disputed.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A J van Boven, J Brügemann, P A de Graeff, J F May, H J Crijns. 1996. The 4S study. Implications for prescribing.. https://doi.org/10.2165/00003495-199651040-00001

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Evaluation of surrogate endpoints in randomized experiments with mixed discrete and continuous outcomes.

A statistical definition of surrogate endpoints as well as validation criteria was first presented by Prentice. Freedman et al. supplemented these criteria with the so-called proportion explained. Buyse and Molenberghs pointed to inadequacies of these criteria and suggested a new definition of surrogacy based on (i) the relative effect linking the overall effect of treatment on both endpoints and (ii) an individual-level measure of agreement between both endpoints. Using data from a randomized trial, they showed how a potential surrogate endpoint can be studied using a joint model for the surrogate and the true endpoint. Whereas Buyse and Molenberghs restricted themselves to the fairly simple cases of jointly normal and jointly binary outcomes, we treat the situation where the surrogate is binary and the true endpoint is continuous, or vice versa. In addition, we consider the case of ordinal endpoints. Further, Buyse et al. extended the approach of Buyse and Molenberghs to a meta-analytic context. We will adopt a similar approach for responses of a mixed data type.

Anticholesteremic Agents↗

Cerebrovascular disease and statins: a potential addition to the therapeutic armamentarium for stroke prevention.

Cerebrovascular disease is the leading cause of disability in Western societies. In the United States, it has been estimated that a stroke occurs every 53 seconds. Consequently, the societal costs attributable to cerebrovascular disease are immense and encourage the medical community to seek new therapies that can reduce stroke's frequency and impact. Although serum lipid levels have not been shown to act as a surrogate marker for stroke, in landmark lipid-lowering trials, statin therapy has been associated with reductions in the incidence of ischemic stroke in patient populations with manifest ischemic heart disease. This observation is supported by a recently published meta-analysis of statin trials that reported an average reduction of about 30% in the incidence of cerebrovascular disease. However, to date, statin studies have only been conducted in patients with, or at high risk for coronary artery disease, who are not truly representative of the overall stroke population. The ongoing Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) trial has been designed to prospectively evaluate the benefits of aggressive lipid-lowering therapy on cerebrovascular events in patients who have had a previous stroke or transient ischemic attack, but who have no prior history of coronary artery disease.

Anticholesteremic Agents↗