In the United States, coronary heart disease (CHD) and cardiovascular disease (CVD) account for nearly 40% of all deaths each year. Coronary heart disease (CHD) continues to be the leading cause of mortality and a significant cause of morbidity among North Americans. In 2003, CHD claimed 653,000 lives, translating into about one out of every five deaths in the United States.¹ High levels of cholesterol, or hypercholesterolemia, are an important risk factor for CHD. The 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors, also known as statins, are the most effective class of drugs for lowering serum low-density lipoprotein cholesterol (LDL-c) concentrations.

They are first-line agents for patients who require drug therapy to reduce serum LDL-c concentrations. The statins work by blocking an enzyme, HMG-CoA reductase that is the rate-limiting step in the manufacture of cholesterol. Statins reduce LDL-cholesterol, total cholesterol, and triglycerides and slightly increase high-density lipoprotein (HDL-c). Statins may also have anti-inflammatory effects. A recent good-quality systematic review found that all statins are equally effective at lowering C-reactive protein levels, but do not affect fibrinogen or several other markers of inflammation.² No study has evaluated whether the effect of statins on any marker is related to their effect on cardiovascular outcomes.

The third report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III {ATP-III}) was released in September 2002,³ and updated in August 2004 to include evidence from more recent trials.⁴ The report stresses that the intensity of treatment should be directed by the degree of cardiovascular risk. Target LDL-c levels depend on the patient's risk of heart disease, medical history, and initial LDL-c level. For most patients who are prescribed a statin, the target will be <130mg/dL or <100mg/dL. In ATP-III, patients who have type 2 diabetes without CHD; peripheral or carotid vascular disease; and patients who have multiple risk factors and a 10-year risk of CHD > 20% are said to have "CHD equivalents," meaning that the criteria for using drug therapy and the LDL target (<100mg/dL) is the same as for patients who have a history of CHD. An LDL-C goal of <70mg/dL for high-risk patients is a therapeutic option. Factors that place patients in the category of very high risk favor a decision to reduce LDL-C levels to <70mg/dL. These factors are the presence of established CVD plus (1) multiple major risk factors (especially diabetes), (2) severe and poorly controlled risk factors (especially continued cigarette smoking), (3) multiple risk factors of the metabolic syndrome (especially high triglycerides >200mg/dL plus non-HDL-C >130mg/dL with low HDL-C {<40mg/dL}), and (4) patients with acute coronary syndromes. The optional goal of <70mg/dL does not apply to individuals who are not high risk.

The 2006 update of the American Heart Association /American College of Cardiology consensus statement on secondary prevention states, "…low-density lipoprotein cholesterol (LDL-C) should be <100 mg/dL for all patients with CHD and other clinical forms of atherosclerotic disease, but in addition, it is reasonable to treat to LDL-C <70 mg/dL in such patients." They assigned this recommendation a grade of II-1 meaning "…there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment [but the]…weight of evidence/opinion is in favor of usefulness/efficacy." The AHA/ACC guidelines qualify this recommendation as follows:

When the <70-mg/dL target is chosen, it may be prudent to increase statin therapy in a graded fashion to determine a patient's response and tolerance. Furthermore, if it is not possible to attain LDL-C <70 mg/dL because of a high baseline LDL-C, it generally is possible to achieve LDL-C reductions of >50% with either statins or LDL-C–lowering drug combinations. Moreover, this guideline for patients with atherosclerotic disease does not modify the recommendations of the 2004 ATP III update for patients without atherosclerotic disease who have diabetes or multiple risk factors and a 10-year risk level for CHD >20%. In the latter 2 types of high-risk patients, the recommended LDL-C goal of <100 mg/dL has not changed. Finally, to avoid any misunderstanding about cholesterol management in general, it must be emphasized that a reasonable cholesterol level of <70 mg/dL does not apply to other types of lower-risk individuals who do not have CHD or other forms of atherosclerotic disease; in such cases, recommendations contained in the 2004 ATP III update still pertain." 5

Six statins are available in the US and Canada:

• Atorvastatin (Lipitor)
• Fluvastatin (Lescol), fluvastatin extended release (Lescol XL)
• Lovastatin (Mevacor), lovastatin extended release (Altoprev)
• Pravastatin (Pravachol)
• Rosuvastatin (Crestor)
• Simvastatin (Zocor)

Fluvastatin and lovastatin are available in extended-release as well as immediate-release forms. In August 2004, the name of the extended release formulation of lovastatin was changed to Altoprev. Lovastatin and pravastatin are natural statins found in fungi; simvastatin is a semisynthetic statin based on lovastatin; and atorvastatin, fluvastatin, and rosuvastatin are fully synthetic.

Usual starting doses are rosuvastatin 10mg, atorvastatin 10mg, pravastatin 40mg, and 20mg of the other statins. The maximum daily dose for rosuvastatin is 40mg. For all other statins, the maximum FDA-approved daily dose is 80mg. For lovastatin and pravastatin, the maximum dose usually is prescribed as 40mg twice a day.