Statins for Everyone?

Karia, Bhalla & Stanley


Cardiovascular disease is responsible for one in three deaths globally (1). It is estimated that by the end of 2010 it will be the leading cause of death in developing countries (2). NICE guidelines state that those already established with coronary heart disease (CHD), cerebrovascular disease and those with established risk factors such as diabetes mellitus should be considered for treatment with a statin.

But what, if any, is the role of statin therapy for patients at low cardiovascular risk (i.e. primary prevention)? Would any benefit be clinically efficacious, safe and cost effective? The key question is: should GPs be prescribing statins for ‘healthy’ patients at low cardiovascular risk?

This controversial topic was in part answered by the recent published JUPITER (Justification for the Use of Statins in Primary Prevention: an Interventional Trial Evaluating Rosuvastatin) study(3).

JUPITER was a large placebo-controlled RCT that included 17802 ‘healthy’ individuals from 26 countries. The study recruited healthy people with normal LDL levels (<3.4mmol/l) but with elevated levels of C-reactive protein (C-RP) (>2mg/L). The mean age of the study population was 66 years. Those with definitive cardiovascular risk factors were excluded as well as those with inflammatory conditions (e.g. arthritis). Study participants were given rosuvastatin 20mg daily or placebo. The primary endpoint was a composite of myocardial infarction, stroke, arterial revascularisation, hospitalisation for unstable angina, or death from cardiovascular causes. The study was supported by AstraZeneca.

C-RP is an inflammatory marker reflecting active inflammation. Elevated C-RP levels are associated with an increased risk of myocardial infarction(4) thus supporting the possible relationship between inflammation and atherosclerosis.

The study was stopped after 1.9 years, because of a clear benefit seen in the rosuvastatin group. Rosuvastatin decreased the relative risk of the primary end point by 44% (95% CI 0.46 to 0.69). Those with a family history of premature CHD had an even greater relative risk reduction in the primary end point of about 65%.

Similar results were obtained from a sub study of the AFCAPS/TexCAPS trial; a five-year study of 5742 participants compared lovastatin to placebo and demonstrated reduced coronary events in a population with a normal lipid profile and elevated C-RP(5).

From the evidence, advantages of giving statins to all include:

? JUPITER found that rosuvastatin reduced LDL-cholesterol levels by 50%, decreasing from a median 108mg/dL at baseline to 55mg/dL at 12 months. CRP levels were also significantly reduced, declining from 4.2mg/L at baseline to 2.2mg/L at 12 months.

? Rosuvastatin significantly reduced the incidence of major cardiovascular events, a population that were mostly below the threshold for treatment according to current prevention guidelines.

? Despite previous concerns regarding the side-effect profile of potent statin therapy, JUPITER found the side-effects for rosuvastatin were no higher than placebo suggesting the rate of side-effect occurrence was low.

? The study included populations that had not been previously well represented in studies; therefore there is no doubt that all these populations share the benefit of cholesterol lowering.

But reasons why giving statins to all is questionable:

? The population studied in JUPITER needs careful evaluation. They were elderly, at least 40% had the metabolic syndrome (but none were overtly diabetic); 16% were taking aspirin prior to entry into the study and at least 10% have a family history of premature cardiovascular disease

? Compliance with taking statins may be a problem due to the side effects of myalgia: GPs often report higher prevalence than clinical trials

? Not all ‘healthy’ individuals have elevated C-RP levels

? There are many ways to decrease the risk of coronary events. Modifiable risk factors such as obesity and smoking should be addressed. By prescribing a statin, individuals may not appreciate the need to address lifestyle changes

? From JUPITER, 25 people would have to take a rosuvastatin over 5 years to prevent one new major cardiovascular event. This needs to be balanced against the cost of drug therapy and monitoring

The use of statins is ubiquitous and has proven benefit for secondary prevention and primary prevention for patients at high cardiovascular risk (defined as a 20% risk of an event over 10 years). The data from JUPITER is exciting, but does not provide a convincing reason to prescribe statins to the worried well, even those with an elevated C-RP. Although C-RP level may be a future determinant in deciding statin therapy, the population under study were mostly elderly and a significant number had soft markers of cardiovascular risk.

In terms of cost effectiveness the cost needs to consider the potential risks and subsequent monitoring.

Finally, the danger of statin therapy might be to lower patients’ acceptance to undertake lifestyle advice. Although strict dieting has only a small reducing effect on LDL-cholesterol, lifestyle measures, if taken as a whole significantly reduces cardiovascular events (6).


(1) WHO. CVD-Risk Management Package for low- and medium resource settings page 3 [accessed 8th June 2009]

(2) World health Organisation. Strategic priorities of the WHO Cardiovascular Disease programme [accessed 8th June 2009]

(3) Ridker P, Danielson E, Fonseca F, Genest J, Gotto A, Kastelein J et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C - reactive protein. New England Journal of Medicine. 2008 359(21): 2195-2207

(4) Dibra A, Mehilli J, Schwaiger M, Schühlen H, Bollwein H, Braun S et al. Predictive value of basal C-reactive protein levels for myocardial salvage in patients with acute myocardial infarction is dependent on the type of reperfusion treatment. European Heart Journa.l 2003 24(12):1128-1133

(5) Ridker P, Rifai N, Clearfeild M, Downs J, Weis S, Miles S et al. Measurement of C - reactive protein for the Targeting of Statin Therapy in the Primary Prevention of Acute Coronary Events. New England Journal of Medicine. 2001 244(26) 1959-1965

(6) Sdringola S, Nakagawa K, Nakagawa Y, Yusuf S, Boccalandro F, Mullani N et al. Combined intense lifestyle and pharmacologic lipid treatment further reduce coronary events and myocardial perfusion abnormalities compared with usual-care cholesterol-lowering drugs in coronary artery disease. Journal of the American College of Cardiology. 2003 41(02):263-272


All Authors:

Author 1:
Roshni Karia
Leicester Medical School

Author 2:
Divya Bhalla
Leicester Medical School

Dr Adrian Stanley
Consultant Physician
Department of Cardiovascular Sciences,
University of Leicester,
Robert Kilpatrick Clinical Sciences Building,
Leicester Royal Infirmary,


Copyright Priory Lodge Education Limited 2009

First Published September 2009

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