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Lowering serum cholesterol has become one of our most powerful tools for controlling cardiovascular disease. Randomized trials of tens of thousands of patients have demonstrated the efficacy and safety of statins in reducing the risk of myocardial infarction, stroke, and cardiac death.
But questions remain:
Who should be treated?
What is the right goal LDL level?
Which drugs should I choose?
Despite the nation's massive investment in managing cholesterol, we frequently miss the mark: diet and exercise messages go unheeded, medications are often underused, drug choices are sometimes arbitrary, and only a minority of patients reach their treatment goals. Better control of serum lipids presents an opportunity to improve care, reduce morbidity and mortality, and optimize therapeutic choices.
A fasting lipoprotein profile including total cholesterol, LDL, and HDL should be measured in all adults 20 years and older, at least once every 5 years.
Identify patients with coronary artery disease (CAD) or the following "risk equivalents": symptomatic carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm, or diabetes. Any of these puts the patient at over 20% risk of having a coronary event in the next ten years.
Assess other risk factors:
Calculate risk: For patients without CAD or a CAD "risk equivalent," but who have two or more of these other risk factors, estimate the 10-year CAD risk using the Framingham scores (see accompanying evidence document, or online resources such as http://hp2010.nhlbihin.net/atpiii/calculator.asp)
All patients with LDL levels greater than their goal should begin TLC by increasing physical activity, reducing weight when appropriate, stopping smoking, and improving diet). Clinicians should actively encourage these behavior changes and monitor folow-up cholesterol levels to determine whether medication therapy is necessary. Practical recommendations about diet and exercise are on the American Heart Association website: http://www.americanheart.org/presenter.jhtml?identifier=4764.
Statins are all members of the same therapeutic class, but no published head-to-head studies have compared statins at equipotent doses (e.g., atorvastatin 10 mg vs. simvastatin 40 mg) in achieving clinically important outcomes. Most statins reduce CAD events better than placebo, and seem to have the same risk of side effects at comparable doses.2,3,4 Therefore, at equivalent dose intensities, most statins will likely produce equivalent results.
As a result, which statin to prescribe should be based primarily on: (1) the extent of LDL lowering required to get to goal for a given patient, and (2) affordability.
Despite their clinical similarity, statins do differ substantially in price, and affordability is a major factor in compliance. Therefore, when choosing among statins of equivalent potency, cost may be a relevant consideration.
A review of the current literature indicates that:
Ezetimibe is not a statin, and it lowers LDL by a completely different mechanism. Unlike the statins, it has never been shown to protect against real clinical outcomes such as MI or stroke; it was approved solely on the basis of its ability to influence the surrogate marker of LDL levels. As a result, there is little clinical trial evidence that a patient whose LDL is lowered with these products will havr the same actual benefit that would be achieved by reaching that goal through better-established drugs (statins). Published results of clinical trials studying this question are still years away. Therefore, at present, clinical efforts should be directed at reducing a patient's LDL to target levels using statins alone. If an additional agent is needed, add another drug that has been shown to have clinical benefits (e.g., nicotinic acid, bile sequestrants, or fibrates - monitoring closely for myopathy if fibrates are used).5 Reserve ezetimibe for the rate patient who cannot tolerate statins or cannot get to LDL goal despite these steps.
The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) examined whether statins can benefit men aged >50 and women aged >60 years who have high-sensitivity C-reactive protein (hs-CRP) >2.0 mg/L but normal cholesterol levels (LDL <130 mg/dL).6 It found that statin therapy substantially reduced the primary outcome (a composite of MI, stroke, arterial revascularization, hospitalization for unstable angina, or death from CV causes) by 44% (p<0.00001).
While JUPITER was conducted using rosuvastatin (Crestor), there is good evidence from previous clinical trials that other statins are also effective in lowering C-reactive protein.7
This material was produced by Niteesh K. Choudhry, M.D., Ph.D., Assistant Professor of Medicine, Harvard Medical School; Michael A. Fischer, M.D., M.S., Assistant Professor of Medicine, Harvard Medical School; Leslie Jackowski, B.Sc.(Hon.), M.B.B.S. (M.D.), Senior Clinical Consultant, Harvard University; and William H. Shrank, M.D., M.S.H.S., Assistant Professor of Medicine, Harvard Medical School. Senior editor: Jerry Avorn, M.D., Professor of Medicine, Harvard Medical School. Drs Avorn, Choudhry, Fischer, and Shrank are all physicians at the Brigham and Women's Hospital in Boston. None of the authors accepts any personal compensation from any drug company.
The Independent Drug Information Service (iDiS) is supported by the PACE Program of the Department of Aging of the Commonwealth of Pennsylvania, the Massachusetts Department of Public Health, and the Washington, D.C. Department of Health.
This material is provided by The Alosa Foundation, a nonprofit organization that is not affiliated in any way with any pharmaceutical company.
These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient's clinical condition.
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