Lipid-lowering therapy

Pushing down cholesterol...

Lowering serum cholesterol has become one of our most powerful tools for controlling coronary artery disease. Randomized trials of tens of thousands of patients have demonstrated the efficacy and safety of statins in reducing the risk of myocardial infarction and cardiac death.

But pressing questions remain:
Who requires treatment?
What is the right LDL goal?
Which drugs should I choose?

Despite the nation's massive investment in managing cholesterol, we frequently miss the mark: 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.

In which patients should I check serum lipids, and how?

A fasting lipoprotein profile should be measured in all adults 20 years and older, at least once every 5 years.

Who needs to be treated?1,2

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 these risk factors:

  • cigarette smoking
  • hypertension (BP >140/90 mm/Hg, or taking an antihypertensive medication)
  • low HDL-cholesterol (<40 mg/dL) - elevation of protective HDL-cholesterol >60 mg/dL counts as a "negative" risk factor
  • family history of premature CAD (in male first degree relative <55 years, in female first degree relative <65 years)
  • age (men >45 years, women >55 years)

Calculate risk: For patients without CAD or a "risk equivalent," but who have two or more positive risk factors, estimate the 10-year CAD risk using the Framingham point scores (see lipid-lowering monograph, or online resources such as

How can I help my patients with therapeutic lifestyle changes ("TLC")?

All patients with LDL levels greater than their goal should begin TLC (i.e., increase physical activity, reduce weight when appropriate, stop smoking, and improve diet). Clinicians should provide counseling about TLC and perform follow-up cholesterol monitoring to assess whether medication therapy is necessary. Useful recommendations about diet and exercise are on the American Heart Association website:

If a drug is needed, which statin should I prescribe?

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 compared to placebo, and seem to have the same risk of side effects at comparable doses.3 (An important exception is rosuvastatin [Crestor], for which there is minimal evidence of benefit in achieving true clinical outcomes.) 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.

Various statins can be used to achieve specific reductions in LDL. Lovastatin (Mevacor and generics) and fluvastatin (Lescol) generally produce less LDL reduction per mg of drug administered, but this may be adequate to get many patients to their goal. On the other hand, atorvastatin (Lipitor), rosuvastatin (Crestor), and simvastatin with ezetimibe (Vytorin) produce the greatest LDL reduction per mg of drug, though this may be more than is needed by many patients.

Despite their clinical similarity, statins do differ substantially in cost. Simvastatin (Zocor) recently became available generically, the highest-potency statin to do so. When more generic versions of it are on the market, its cost is expected to drop considerably.

What about high-intensity therapy?

Some recent trials have evaluated reducing LDL to very low levels.4-8 A review of the current literature suggests the following conclusions:

  • High-intensity lipid lowering seems to be more effective than usual-dose statins for patients with acute coronary syndrome and stable CAD, and is equally safe.
  • These trials achieved LDL levels of about 75 mg/dL, supporting the recommended "optional" goal of 70 mg/dL for patients with CAD.
  • Recent stroke and TIA should be treated as coronary disease equivalents.

When should I address high triglycerides and/or the metabolic syndrome?

For most patients with elevated triglycerides, LDL management is the primary goal. If triglycerides are >150 mg/dL after reaching the LDL goal, additional treatment should be considered to address this. For patients with triglycerides >500 mg/dL, management of triglycerides becomes the primary goal, in order to reduce the likelihood of pancreatitis.

Some patients with high cholesterol may also have the metabolic syndrome (also known as "Syndrome X"), diagnosed when three or more of the following are present: abdominal obesity (waist circumference >40 inches for men and >35 inches for women), elevated triglycerides (>150 mg/dL), low HDL (<40 mg/dL for men and <50 mg/dL for women), elevated blood pressure (>130/85 mm/Hg), and elevated fasting glucose (>110 mg/dL). For these patients, exercise, low-fat and low-cholesterol diets, and aspirin should be recommended, and elevated blood pressure, triglycerides and glucose should be treated when appropriate.

This material was produced by Niteesh K. Choudhry, M.D., Ph.D., Instructor of Medicine, Harvard Medical School, and William H. Shrank, M.D., M.S.H.S., Instructor of Medicine, Harvard Medical School. Senior editor: Jerry Avorn, M.D., Professor of Medicine, Harvard Medical School. The Independent Drug Information Service (iDiS) is supported by the PACE Program of the Department of Aging of the Commonwealth of Pennsylvania. This program is provided by the Alosa Foundation and 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.


  1. National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-421.
  2. Grundy SM, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227-39.
  3. Helfand M, et al. Drug Class Review on HMG-CoA Reductase Inhibitors (Statins). Obtained October 2006 at:
  4. de Lemos JA, et al. Early intensive vs. a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of A to Z trial. JAMA. 2004;292:1307-16.
  5. Cannon CP, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495-504.
  6. LaRose JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425-35.
  7. Pedersen TR, et al. High-dose atorvastatin vs. usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294:2437-45.
  8. Amarenco P, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549-59.