Contemporary Issue
Statins: Can we advocate them for primary prevention of heart disease?

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Abstract

The discovery of cholesterol-lowering agents, namely HMG-CoA reductase inhibitors or statins, ushered in a series of large cholesterol reduction trials. The first of these studies was the Scandinavian Simvastatin Survival Study (4S) in which hypercholesterolemic men with CHD who were treated with simvastatin had a reduction in major coronary events of 44% and a reduction in total mortality of 30%. Many more secondary prevention trials followed to establish unequivocally the benefit of cholesterol reduction. Strategies that aim to improve primary prevention are important for managing the overall burden of disease. Recently therefore, the role of statin in primary prevention is being debated. The JUPITER trial and more recently the Cholesterol Treatment Trialists collaborators, proved that incidences of first major cardiovascular events in apparently healthy individuals were reduced by statins. Statins have also been discussed to be having certain pleiotropic effects on other diseases like diabetes, cancer and osteoporosis. However, issues of cost effectiveness and adverse effects like myositis, and transaminitis still loom large. The medical community needs to debate and evolve a possible consensus on the path breaking subject.

Introduction

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. High blood cholesterol is associated with CVD and is an important risk factor. Reducing high blood cholesterol or LDL-Cholesterol (LDL-C) by statins, thus remains the medical goal of reducing the chances of suffering a CVD. As is known, for managing the overall burden of a disease, strategies to improve primary prevention should be aimed at. In case it is established that statins can prevent or delay CVS disorders in healthy individuals, it would not only reduce human misery but also will reduce costs of healthcare as treating heart disease is expensive, and in a developing country like ours often out of reach of the majority of the population. Several studies have been carried out to evaluate the cost effectiveness of low-cost generic statins available in the market for primary prevention. Lawrence et al found that primary prevention with statins was cost-saving in different LDL cholesterol thresholds (@160, @130, and @100 mg/dL) and at different levels of cardiovascular risks. They observed that with wide availability of low-cost generics, primary prevention with statins might become less expensive and cost-effective for most persons with even moderate dyslipidemia or with any other lifestyle risk factors.1 In this mini review, we have attempted to analyse the cost effectiveness of using statins as a primary prevention pharmacological agent vis-a-vis its use in secondary prevention, as cited by few of the systematic reviews of recent time.

Section snippets

Statins in secondary prevention

The first important secondary prevention statin trial was the Scandinavian Simvastatin Survival Study (4S Trial). This was essentially a double-blinded randomized control trial. In this study, 4444 patients of angina pectoris or with old MI and cholesterol in the range of 5.5–8.0 mmol/L, on a fat reducing diet, were treated either with simvastatin or placebo and followed up for a period of 5.4 years. The effects of Simvastatin on total cholesterol, LDL-C, and HDL-C were −25%, −35%, and +8%

Statins in primary prevention

Though statins are still approved for use in subjects with established coronary artery disease or at high-risk for coronary events, several studies have expanded the indications of treatment to include persons at progressively lower risk. The breakthrough was in 2008, when the results of the JUPITER (Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin) trial6 showed that patients with high C reactive proteins might benefit from preventive

Beneficence vs harm

The pleiotropic effects of statins, observed in several studies during treatment of cardiovascular disease, should also deserve a mention. Statins, as we know, act through both cholesterol-dependent and cholesterol-independent pathways. Some of these effects involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response14, 15, 16 as depicted in Table 1. Pleiotropic effects have

Conclusion

A wealth of data thus demonstrates that reduction of cholesterol levels is associated with reduction of coronary artery disease risk and the magnitude of the benefit, acting primarily by reducing LDL-C, is greater than that observed with any other lipid-modifying intervention. The recent Cochrane review of statin use for primary prevention supports the conclusion that statins are safe and effective in reducing vascular events and overall mortality even in primary prevention. The benefits were

Conflicts of interest

All authors have none to declare.

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    Available online 30 August 2013

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