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What You Should Know About
Vytorin and the ENHANCE Study
I’ve heard about the ENHANCE drug study in the news. What exactly is it?
The ENHANCE study compared Vytorin to Zocor. Vytorin contains ezetimibe and simvastatin, two medicines that lower LDL (bad) cholesterol. Zocor contains simvastatin only. (Ezetimibe is sold by itself too, as Zetia). The goal of the ENHANCE study was to see if Vytorin reduced plaque build-up in blood vessels better than Zocor. Vytorin wasn’t better than Zocor at reducing plaque build-up, but it was better at lowering LDL cholesterol. It’s important to know that the ENHANCE study only included people with a genetic disorder that causes them to have unusually high levels of cholesterol. It affects about one in 500 people. The average person with high cholesterol probably doesn’t have this disorder. Another important point is that only a small amount of information has been released about the ENHANCE study. Researchers are still analyzing the data. It will be a few months before we know all of the details. I’m taking Vytorin, so what does ENHANCE mean for me?
Right now, this new information probably won’t affect you. Vytorin isn’t better than Zocor at reducing plaque build-up in blood vessels, but it is better at lowering LDL cholesterol. Most importantly, it isn’t known if Vytorin is better or worse than Zocor at preventing heart attacks, strokes, and death. There are studies in progress that will determine this, and the information will be available within the next few years. For now, experts recommend that healthcare providers continue to prescribe medicines necessary to lower LDL cholesterol. No changes should be made based on this latest study.
Is taking Vytorin or Zetia dangerous?
No. The ENHANCE study didn’t show a difference in side effects between Vytorin and Zocor. At this point, there’s no reason to believe that Vytorin or other ezetimibe-containing products are dangerous. Should I stop taking Vytorin or Zetia?
No, not without discussing it with your healthcare provider first. Pharmacist’s Letter / Prescriber’s Letter to give to their patients. Copyright 2008 by Therapeutic Research Center www.pharmacistsletter.com ~ www.prescribersletter.com Detail-Document #240201
−This Detail-Document accompanies the related article published in− PHARMACIST’S LETTER / PRESCRIBER’S LETTER
February 2008 ~ Volume 24 ~ Number 240201 Does Ezetimibe ENHANCE Lipid Therapy?
Background
The primary endpoint for assessing treatment Intense media coverage, including that by lay efficacy was the change in mean carotid artery press, is causing patients and providers to ask intima-media thickness (CA IMT), which is a about ENHANCE (Effect of Combination measurement of plaque build-up and a surrogate Ezetimibe and High-Dose Simvastatin vs. marker for cardiovascular events and stroke. CA Simvastatin Alone on the Atherosclerotic Process IMT measurements weren’t different between the in Patients with Heterozygous Familial two groups at baseline.3 Hypercholesterolemia). This surrogate-marker study compared the effect of Vytorin (simvastatin measured at baseline, six months, 12 months, plus ezetimibe) vs. Zocor (simvastatin) on 18 months, and 24 months. The percent change progression of atherosclerosis.1 ENHANCE from baseline in lipid parameters was included began in 2002 and was completed in 2006. The sponsors, Merck and Schering-Plough, were criticized by a U.S. House Committee for their Preliminary Results
delay in making the results available.2 Ezetimibe After two years of treatment, combination (Zetia [U.S.], Ezetrol [Canada] has racked up therapy with simvastatin/ezetimibe didn’t reduce sales of about 5 billion dollars worldwide (Vytorin progression of CA IMT more than simvastatin costs around $3 per pill compared to about $1 per pill for simvastatin). Understandably, people reduced by 58% in the Vytorin group, compared want to know if Vytorin is really helping them or to 41% in the simvastatin group (p < 0.01). The if it could even hurt them. Providers need to study wasn’t powered to assess the incidence of know what to tell patients and whether the cardiovascular events, but there didn’t appear to be a difference between the treatment groups.3 prescribing practices. This document provides a The incidence of adverse events was similar preliminary review of the ENHANCE study, a patient handout, and a chart that compares What Does It Mean?
When considering the results of ENHANCE, ENHANCE Study Design
the population studied and the outcome measure ENHANCE is the first large trial designed to used are important. The patients studied in assess the effects of combination lipid-lowering therapy compared to statin monotherapy on the hypercholesterolemia (HeFH), and the mean progression of atherosclerosis.1 It was an baseline LDL was 319 mg/dL.1,3 This isn’t the international, randomized, double-blind, population typical of major outcomes studies with controlled trial designed to compare statins (e.g., 4S, AFCAPS/TexCAPS, WOSCOPS, simvastatin/ezetimibe 80 mg/10 mg and etc).4-6 About one in 500 people have HeFH, simvastatin 80 mg. The study lasted for two years which results in very high LDL.7 Individuals with HeFH have about one-half of the LDL receptors included patients between the ages of 30 and compared to those without the disorder, and they 75 years with heterozygous familial are at high risk for early CHD (often fourth or hypercholesterolemia (HeFH). Those who were fifth decade).7 Most cases require two or three included had LDL of greater than 210 mg/dL after drugs to lower LDL within guideline range.7 Some question whether the additional lipid- Copyright 2008 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #240201: Page 2 of 4)
lowering effect of Vytorin compared to guidelines (LDL <100 mg/dL for high-risk, and simvastatin was enough to impact CA IMT in this <70 mg/dL for very high-risk patients [U.S.], LDL Carotid artery intima-media thickness (CA [Canada]).7,16,17 (Note that the LDL-lowering IMT), the measurement used as the primary effect of Vytorin in the ENHANCE study is what endpoint in ENHANCE, is widely used as a you would expect to see with the addition of surrogate marker for atherosclerotic disease. It ezetimibe to a statin). Statins are the most correlates with existing cardiovascular disease and effective cholesterol-lowering drugs and should is predictive of cardiovascular disease in be considered first-line for lowering LDL individuals without clinically evident disease.8 Statins have been shown to reduce or reverse CA Rosuvastatin (Crestor), at the highest dose of IMT progression.8 Currently there is more 40 mg, lowers LDL by 62%. This is the most that evidence for LDL as a surrogate marker for heart can be expected from a statin. Adding ezetimibe disease than there is for CA IMT, but experts to a statin can reduce LDL by up to an additional point out that surrogate markers in general are a 19%. The addition of a bile acid sequestrant to a “slippery slope.”9 For example, supplementation statin can reduce LDL by another 10% to 20%. with folic acid and vitamins B6 and B12 reduces Niacin reduces LDL by another 12% to 14%.18 CA IMT. But these vitamins don’t have a benefit But keep in mind that like Vytorin, other on cardiovascular outcomes.10,11 Hormone combination therapies for hypercholesterolemia replacement therapy can reduce CA IMT, but it can also increase risk for strokes.12 Another Ezetimibe isn’t necessarily more expensive ongoing debate is whether LDL-lowering or the than other cholesterol-lowering agents and it’s multiple biologic effects of statins are actually considered to be well tolerated. Bile acid sequestrants, for example, cost more than There has been buzz in the media about an ezetimibe. They run between $120 and $250 per undisclosed risk of liver damage with ezetimibe. month (AWP), plus they have GI side effects. The preliminary data from ENHANCE didn’t Ezetimibe costs around $90 for a one-month show a higher than expected risk with the combination, or a risk that was higher than with simvastatin monotherapy.3 These data are Conclusion
consistent with Vytorin product labeling.13 For now, experts recommend that providers continue to follow current guidelines for lowering Bottom Line
cholesterol. Let patients know that they aren’t in Keep in mind that the ENHANCE results are danger if they’re using an ezetimibe-containing still being analyzed. It will be important to see product, and not to discontinue their medication the full report of ENHANCE before a change in without discussing it with their healthcare practice can even be considered. At this point, we provider first. Make sure patients know that don’t know if confounders like smoking, ENHANCE is just one piece of the puzzle, and hypertension, etc. were taken into consideration. Some experts are anxious to see whether there are Users of this document are cautioned to use their own The American College of Cardiology (ACC) professional judgment and consult any other necessary and the American Heart Association (AHA) both or appropriate sources prior to making clinical note that ENHANCE is an imaging study, not an judgments based on the content of this document. Our outcomes study and that conclusions should not editors have researched the information with input be drawn until large clinical outcome trials like from experts, government agencies, and national IMPROVE-IT are published over the next two to organizations. Information and Internet links in this three years.14,15 This will show whether or not article were current as of the date of publication. combining ezetimibe with a statin has a benefit on Until more is known, experts recommend to continue aiming for LDL goals as per current Copyright 2008 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #240201: Page 3 of 4)
Levels of Evidence
Implications of recent clinical trials for the National In accordance with the trend towards Evidence-Based Cholesterol Education Program Adult Treatment Medicine, we are citing the LEVEL OF EVIDENCE
http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3 Level Definition
High-quality randomized controlled trial (RCT) 8. Kastelein JJ, Wiegman A, de Groot E. Surrogate High-quality meta-analysis (quantitative markers of atherosclerosis: impact of statins. 9. Hughes S. ENHANCE saga continues: experts dispute ezetimibe’s future and “weight” of imaging www.theheart.org/article/837867.do. January 16, 10. Till U, Rohl P, Jentsch A, et al. Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, vitamins B6 and B12. Atherosclerosis Pharmacist's Letter/Prescriber's Letter Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65:251-8. 12. Takahashi K, Tanaka E, Murakami M, et al. Long- term hormone replacement therapy delays the age Project Leader in preparation of this Detail-
related progression of carotid artery intima-media Document: Stacy A. Hester, R.Ph., BCPS,
thickness in healthy postmenopausal women. 13. Product information for Vytorin. Merck/Schering- Plough. North Wales, PA 19454. May 2007. References
14. Anon. ACC statement on ENHANCE trial. 1. Kastelein JJ, Sager PT, de Groot E, Veltri E. Comparison of ezetimibe plus simvastatin versus www.acc.org/enhance.htm. (Accessed January 18, simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia. 15. Anon. Statement from the American Heart Design and rationale of the Ezetimibe and Association on ENHANCE study results. American Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial. Am www.americanheart.org/presenter.jhtml?identifier= 3053094. January 15, 2008. (Accessed January 2. Hughes S. U.S. House Committee raises concerns 16. Antman EM, Anbe DT, Armstrong PW, et al. www.theheart.org/article/833387.do. December ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction- 3. Hughes S. ENHANCE results yield disappointment executive summary. Circulation 2004;110:588- www.theheart.org/article/837243.do. January 14, 17. McPherson R, Frohlich J, Fodor G, Genest J. Canadian Cardiovascular Society position 4. Scandinavian Simvastatin Survival Study Group. statement-Recommendations for the diagnosis and Randomized trial of cholesterol lowering in 4444 treatment of dyslipidemia and prevention of patients with coronary heart disease: the cardiovascular disease. Can J Cardiol Scandinavian Simvastatin Survival Study (4S). 5. Downs JR, Beere PA, Whitney E, et al. Design Letter/Prescriber’s Letter 2006;22(8):220802. and rationale of the Air Force/Texas Coronary (AFCAPS/TexCAPS). Am J Cardiol 1997;80:287- 6. Shepard J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301-7. Copyright 2008 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #240201: Page 4 of 4)
Cite this Detail-Document as follows: Does ezetimibe ENHANCE lipid therapy? Pharmacist’s
Letter/Prescriber’s Letter 2008;24(2):240201.

Evidence and Advice You Can Trust… 3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright 2008 by Therapeutic Research Center Subscribers to Pharmacist’s Letter and Prescriber’s Letter can get Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com or www.prescribersletter.com
Detail-Document #260611
−This Detail-Document accompanies the related article published in− PHARMACIST’S LETTER / PRESCRIBER’S LETTER
Characteristics of the Various Statins
-Based on U.S. product labeling and relevant studies. Canadian product information given if differs (i.e,. more conservative) from U.S.- View our helpful chart, Non-Statin Lipid-Lowering Agents Druga Potency
(average
Liver Function
Selected Drug Interactions
Cost/month
decrease in
Considerations
Monitoring
Canada)b
that significantly inhibit its metabolism Rifampin may increase or decrease levels, depending on timing. labelling advises caution with fibrates.) Concomitant rifampin decreases fluvastatin levels. Copyright 2010 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #260611: Page 2 of 9)
Druga Potency
(average
Liver Function
Selected Drug Interactions
Cost/month
decrease in
Considerations
Monitoring
Canada)b
that significantly inhibit its metabolism cyclosporine, and grapefruit juice; dose 40 mg (20 mg Altoprev) daily with extended-release niacin (Niaspan). Do patients [more frequent with 40 mg or more].) (GFR) 30 to <60 weeks after initiation or Copyright 2010 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #260611: Page 3 of 9)
Druga Potency
(average
Liver Function
Selected Drug Interactions
Cost/month
decrease in
Considerations
Monitoring
Canada)b
cytochrome P450 and may be less likely $25.99/ checking at baseline, and risk/benefit decision. labelling advises 12 weeks after initiation daily doses >40 mg in renal impairment.) rosuvastatin dose reduction with niacin. Copyright 2010 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #260611: Page 4 of 9)
Druga Potency
(average
Liver Function
Selected Drug Interactions
Cost/month
decrease in
Considerations
Monitoring
Canada)b
cyclosporine, and grapefruit juice; dose (Niaspan) or diltiazem. Do not exceed 10 mg daily with gemfibrozil. Use caution with fenofibrate. a. The following product labeling was used for the above chart: Lipitor (February 2010), Lescol/Lescol XL (December 2009), Mevacor (September
2008), Altoprev (December 2006), Livalo (August 2009), Pravachol (March 2007), Crestor (February 2010), Zocor (May 2010), Lipitor Canada (July
2009), Lescol/Lescol XL Canada (December 2008), Mevacor Canada (December 2008), Pravachol Canada (December 2008), Crestor Canada
(October 2009), Zocor Canada (December 2008).
b. U.S. cost is from drugstore.com at time of writing. Cost is for generic if available.
Abbreviations: ACS = acute coronary syndrome; CHD = coronary heart disease; HDL = high-density lipoprotein cholesterol; LDL = low-density
lipoprotein cholesterol; MACE = major adverse cardiac event (cardiac death, non-fatal MI, or revascularization); MI = myocardial infarction; PCI =
percutaneous coronary intervention; TIA = transient ischemic attack. Evidence is Level A for all studies except CARDS, FLORIDA, TREADMILL
[Level A/B] and GREACE and L-CAD [Level B].
Clinical Benefit of Statins (Study acronym in parentheses; FDA-labeled indications are underlined. )
Atorvastatin (Lipitor)
▪ Primary prevention of CHD: Reduces non-fatal MI and fatal CHD, and stroke in patients with hypertension and total cholesterol <250 mg/dL
(ASCOT).
▪ Primary prevention of CHD in diabetes: Reduces stroke and MI in patients with type 2 diabetes, an additional CHD risk factor, and LDL <160
mg/dL. (CARDS).
▪ Secondary prevention of CHD: 80 mg/day reduced risk of major cardiovascular events in patients with CHD and LDL<130 mg/dL vs 10 mg. No
overall mortality difference (TNT).

Continued
Copyright 2010 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #260611: Page 5 of 9)
Atorvastatin (Lipitor), continued
▪ Secondary prevention of CHD: 80 mg/day reduced risk of non-fatal cardiovascular events vs simvastatin 40-80 mg/day in patients with CHD and
previous MI (mean LDL 121.5 mg/dL) (IDEAL).
▪ Secondary prevention of CHD:* Reduced risk of coronary morbidity and mortality, and stroke in open-label comparison with usual care of patients
with LDL >100 mg/dL (GREACE). (*Note: GREACE not used to support this indication.)
▪ 80 mg/day begun within 1 to 4 days after ACS reduced recurrent ischemic events and stroke over 4 months (MIRACL).
▪ In ACS, intense lipid lowering (median LDL 62 mg/dL) lowers risk of death/major cardio events more than moderate lipid lowering (median LDL
95 mg/dL) (PROVE-IT).
▪ Regresses/slows progression of atherosclerosis (ASAP, ARBITER, REVERSAL).
▪ Unclear benefit in peripheral arterial disease (TREADMILL).
Fluvastatin (Lescol)
▪ Slows progression of atherosclerosis in patients with CHD and mild to moderate hypercholesterolemia (LCAS).
▪ Secondary prevention of CHD: Reduces need for revascularization. Dose of 40 mg twice daily reduced risk of MACE when begun within days after
PCI in patients with average cholesterol levels (LIPS).
▪ Did not reduce MACE in renal transplant recipients; but secondary endpoints of cardiac death and MI were reduced (ALERT).
▪ No benefit for early treatment of ACS with 80 mg/day (FLORIDA).
Lovastatin (Mevacor)
▪ Primary prevention of CHD: Reduces first acute coronary event, MI, unstable angina, and revascularization in patients with average LDL
(AFCAPS/ TexCAPS).
▪ Slows progression of coronary atherosclerosis in CHD (CCAIT, FATS, MARS). Improvement also in carotid arteries (ACAPS).
Copyright 2010 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #260611: Page 6 of 9)
Pitavastatin (Livalo)

▪ Pitavastatin 4 mg and atorvastatin 20 mg similarly reduce nonculprit coronary plaque volume post-ACS (JAPAN-ACS).
Pravastatin (Pravachol)
▪ Primary prevention of CHD: Reduces cardiovascular death, MI, and revascularization in patients with high LDL and multiple risk factors
(WOSCOPS).
▪ Secondary prevention of CHD: Reduces recurrent MI, coronary death, revascularization, and stroke/TIA across range of cholesterol levels (CARE,
LIPID).
▪ Slows progression of coronary atherosclerosis in CHD; improvement also in carotid arteries (REGRESS, PLAC I, PLAC II, KAPS).
▪ Failed to show benefit in hypertensive patients (ALLHAT-LLT), but result probably due to high non-study statin use in usual care group.
▪ Preliminary study found lower risk of MACE with early therapy of ACS (L-CAD).
▪ Reduced composite of coronary death, non-fatal MI, and stroke in high-risk patients >70 years old, but no benefit for stroke alone; result attributed
to short study duration (PROSPER).
Rosuvastatin (Crestor)
▪ Regression of atherosclerosis with intensive statin therapy in patients with angiographic coronary disease.
▪ 40 mg/day reduced LDL (mean 60.8 mg/dL), raised HDL (mean 49.0 mg/dL), and reduced percent mean atheroma volume by 0.98% (ASTEROID).
▪ Slows progression of atherosclerosis (METEOR).
▪ Primary prevention of CAD: Reduces MI, stroke, and cardiovascular death in patients with LDL <130 mg/dL and hs-CRP >2 mg/L (JUPITER).
Simvastatin (Zocor)
▪ Primary and secondary prevention of CHD: Reduces risk of total mortality, non-fatal MI, stroke, and revascularization in patients at high risk of
coronary eventsc, but with normal cholesterol (including LDL <100 mg/dL, women, diabetes, and peripheral arterial disease) (HPS).
Continued
Copyright 2010 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #260611: Page 7 of 9)
Simvastatin (Zocor), continued
▪ Secondary prevention of CHD: Reduces recurrent MI, coronary and total mortality, revascularization, and stroke in patients with high LDL (4S).
▪ Slows progression of atherosclerosis in patients with CHD and normal to high cholesterol (MAAS, SCAT).
▪ Combined with niacin reduces major coronary events in patients with CHD and HDL <35 mg/dL (HATS).
▪ Reduces vascular events (HPS) and development/progression of intermittent claudication (4S) in peripheral arterial disease.
c. In patients with CHD or CHD risk-equivalent (diabetes, peripheral arterial disease, history of stroke or other cerebrovascular disease).
Statin Clinical Trials
4S - Scandinavian Simvastatin Survival Study: Lancet 1994;344:1383-9. Am J Cardiol 1998;81:333-5.
ACAPS - Asymptomatic Carotid Artery Progression Study: Circulation 1994;90:1679-87.
AFCAPS/TEXCAPS - Air Force/Texas Coronary Atherosclerosis Prevention Study: JAMA 1998;279:1615-22.
ALERT - Assessment of Lescol in Renal Transplantation Study: Lancet 2003;361:2024-31.
ALLHAT-LLT - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: JAMA 2002;288:2998-3007.
ARBITER - Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: Circulation 2002;106:2055-60.
ASAP - Atorvastatin versus Simvastatin on Atherosclerosis Prevention: Lancet 2001;357:577-81.
ASCOT - Anglo-Scandinavian Cardiac Outcomes Trial: Lancet 2003;361:1149-58.
ASTEROID - A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden: JAMA 2006;295:
(doi:10.1001/jama.295.13.jpc60002).
CARDS - Collaborative Atorvastatin Diabetes Study. Lancet 2004;364:685-96.
CARE - Cholesterol and Recurrent Events Trial: N Engl J Med 1996;335:1001-9.
CCAIT - Canadian Coronary Atherosclerosis Intervention Trial: Circulation 1994;89:959-68. Circulation 1995; 92:2404-10.
FATS - Familial Atherosclerosis Treatment Study: N Engl J Med 1990;323:1289-98.
FLORIDA - Fluvastatin on Risk Diminishing after Acute Myocardial Infarction: [Abstract] Circulation 2000;102:2672d.
GREACE - GREek Atorvastatin and Coronary-heart-disease Evaluation study: Curr Med Res Opin 2002;18:220-8.
HATS - HDL Atherosclerosis Treatment Study: N Engl J Med 2001;345:1583-92.
HPS - Heart Protection Study: Lancet 2002;360:7-22. Lancet 2003;361:2005-16.
IDEAL - Incremental Decrease in End points through Aggressive Lipid lowering. JAMA 2005;294:2437-45.
Copyright 2010 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #260611: Page 8 of 9)
JAPAN-ACS – Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome] study. J Am Coll Cardiol 2009;54:293-302. JUPITER - Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin. N Engl J Med 2008;359:2195-207. KAPS - Kuopio Atherosclerosis Prevention Study: Circulation 1995;92:1758-64. LCAS - Lipoprotein and Coronary Atherosclerosis Study: Am J Cardiol 1997;80:278-86. L-CAD - Lipid-Coronary Artery Disease Study: Am J Cardiol 2000;86:1293-8. LIPID - Long-term Intervention with Pravastatin in Ischaemic Disease: N Engl J Med 1998;339:1349-57. LIPS - Lescol Intervention Prevention Study: JAMA 2002;3215-22. MAAS - Multicentre Anti-Atheroma Study: Lancet 1994;344:633-8. MARS - Monitored Atherosclerosis Regression Study: Ann Intern Med 1993;119:969-76. METEOR - Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin: JAMA 2007;297:1344-53. MIRACL - Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering: JAMA 2001;285:1711-8. PLAC-I - Pravastatin Limitation of Atherosclerosis in the Coronary arteries (PLAC-I): J Am Coll Cardiol 1995;26:1133-9. PLAC-II - Pravastatin Limitation of Atherosclerosis in the Carotid arteries. Am J Cardiol 1995;75:455-9. PROSPER - Prevention of First Stroke: Lancet 2002;360:1623-30. PROVE-IT - Pravastatin or Atorvastatin Evaluation and Infection Therapy: New Engl J Med 2004;350 (early release). REGRESS - Regression Growth Evaluation Study: Circulation 1995;91:2528-40. REVERSAL - Reversal of Atherosclerosis with Aggressive Lipid Lowering. JAMA 2004;291:1071-80. SCAT - Simvastatin/Enalapril Coronary Atherosclerosis Trial: Circulation 2000;102:1748-54. TNT - Treating to New Targets. N Engl J Med 252:1425-35. TREADMILL - Treatment of Peripheral Atherosclerotic Disease with Moderate or Intensive Lipid Lowering: Creager MA, et al [Abstract]. Presented at the 14th International Symposium on Drugs Affecting Lipid Metabolism, New York, September 9-13, 2001. Mohler E, et al. [Abstract]. Presented at the 75th Scientific Sessions of the American Heart Association, Chicago, November 17-20, 2002. WOSCOPS - West of Scotland Coronary Prevention Study: N Engl J Med 1995;333:1301-7. Users of this document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and Internet links in this article were current as of the date of publication. Copyright 2010 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #260611: Page 9 of 9)
Levels of Evidence
Project Leader in preparation of this Detail-
In accordance with the trend towards Evidence-Based Document: Melanie Cupp, Pharm.D., BCPS
Medicine, we are citing the LEVEL OF EVIDENCE
References
Level Definition
1. Statin dose comparison (U.S.). Pharmacist’s High-quality randomized controlled trial (RCT) Letter/Prescriber’s Letter 2009;25(8):260801. High-quality meta-analysis (quantitative 2. Statin dose comparison (Canada). Pharmacist’s Letter/Prescriber’s Letter 2009;5(8):250820. 3. Shitara Y, Sugiyama Y. Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions. Pharmacol Ther 2006;112:71-105. Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65:251-8.
Cite this Detail-Document as follows: Characteristics of the various statins. Pharmacist’s Letter/Prescriber’s Letter
2010;26(6):260611.

Evidence and Advice You Can Trust… 3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright 2010 by Therapeutic Research Center Subscribers to Pharmacist’s Letter and Prescriber’s Letter can get Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com or www.prescribersletter.com

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