In the United States, coronary heart disease and cardiovascular disease account for nearly 40% of all deaths each year. Coronary heart disease continues to be the leading cause of mortality and a significant cause of morbidity among North Americans. In 2006, coronary heart disease claimed 607 000 lives, translating into about 1 out of every 5 deaths in the United States. High levels of cholesterol, or hypercholesterolemia, are an important risk factor for coronary heart disease. 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 concentrations. They are first-line agents for patients who require drug therapy to reduce serum low-density lipoprotein cholesterol concentrations. The purpose of this review is to compare the benefits and harms of different statins in adults and children with hypercholesterolemia.

Contents

• Introduction
  • Purpose and Limitations of Systematic Reviews
  • Scope and Key Questions
  • Inclusion Criteria
• Methods
  • Literature Search
  • Study Selection
  • Data Abstraction
  • Validity Assessment
  • Data Synthesis
  • Peer Review and Public Comment
• Results
  • Overview
  • Report Organization
• Adults
  • Key Question 1. How do statins and fixed-dose combination products containing a statin and another lipid-lowering drug compare in their ability to reduce low-density lipoprotein cholesterol?
  • Key Question 1a. Are there doses for each statin or fixed-dose combination product containing a statin and another lipid-lowering drug that produce similar percent reduction in low-density lipoprotein cholesterol?
  • Key Question 1b. Do statins or fixed-dose combination products containing a statin and another lipid-lowering drug differ in the ability to achieve National Cholesterol Education Program goals?
  • Key Question 2. How do statins and fixed-dose combination products containing a statin and another lipid-lowering drug compare in their ability to increase high-density lipoprotein cholesterol?
  • Key Question 2a. Are there doses for each statin or fixed-dose combination product containing a statin and another lipid-lowering drug that produce similar percent increase in high-density lipoprotein cholesterol between statins?
  • Key Question 2b. Is there a difference in the ability of a statin or fixed-dose combination product containing a statin and another lipid-lowering drug to achieve National Cholesterol Education Panel goals?
  • Key Question 3. How do statins and fixed-dose combination products containing a statin and another lipid-lowering drug compare in their ability to reduce the risk of nonfatal myocardial infarction, coronary heart disease (angina), coronary heart disease mortality, all-cause mortality, stroke, hospitalization for unstable angina, or need for revascularization (coronary artery bypass graft, angioplasty, or stenting)?
  • Key Question 4. Are there differences in effectiveness of statins and fixed-dose combination products containing a statin and another lipid-lowering drug in different demographic groups or in patients with comorbid conditions (e.g., diabetes, obesity)?
  • Key Question 5. Are there differences in the harms of statins or fixed-dose combination products containing a statin and another lipid-lowering drug when used in the general population of adults?
  • Key question 6. Are there differences in the harms of statins or fixed-dose combination products containing a statin and another lipid-lowering drug when used in special populations or with other medications (drug-drug interactions)?
• Children
  • Key Question 1. How do statins and fixed-dose combination products containing a statin and another lipid-lowering drug compare in their ability to reduce low-density lipoprotein cholesterol?
  • Key Question 1a. Are there doses for each statin or fixed-dose combination product containing a statin and another lipid-lowering drug that produce similar percent reduction in low-density lipoprotein cholesterol?
  • Key Question 1b. Do statins or fixed-dose combination product containing a statin and another lipid-lowering drug differ in the ability to achieve National Cholesterol Education Program goals?
  • Key Question 2. How do statins and fixed-dose combination products containing a statin and another lipid lowering drug compare in their ability to raise high-density lipoprotein cholesterol?
  • Key Question 2b. Are there doses for each statin or fixed-dose combination product containing a statin and another lipid lower drug that produce similar percent increase in high-density lipoprotein cholesterol between statins?
  • Key Question 3. How do statins and fixed-dose combination products containing a statin and another lipid lowering drug compare in their ability to reduce the risk of nonfatal myocardial infarction, coronary disease (angina), coronary heart disease mortality, all-cause mortality, stroke, hospitalization for unstable angina, or need for revascularization (coronary artery bypass graft, angioplasty, or stenting)?
  • Key Question 4. Are there differences in effectiveness of statins and fixed-dose combination products containing a statin and another lipid lowering drug in different demographic groups or in patients with comorbid conditions (e.g. diabetes, obesity)?
  • Key Question 5. Are there differences in the harms of statins or fixed-dose combination products containing a statin and another lipid lowering drug when used in the general population of children?
  • Key Question 6. Are there differences in the harms of statins or fixed-dose combination products containing a statin and another lipid lowering drug when used in special populations or with other medications (drug-drug interactions)?
• Summary
• References
• Appendix A Glossary
• Appendix B Search strategy
• Appendix C Methods used to assess quality of studies
• Appendix D Excluded studies
• Appendix E Black box warnings for US Food and Drug Administration-approved drugs
• Evidence Tables

Update 4: August 2006
Update 3: September 2005
Update 2: March 2004
Update 1: July 2003
Original Report: April 2002

The medical literature relating to this topic is scanned periodically. (See http://www.ohsu.edu/ohsuedu/research/policycenter/DERP/about/methods.cfm for description of scanning process). Prior versions of this report can be accessed at the DERP website.

Original authors: Mark Helfand, MD, MPH, Cathy Kelley, PharmD

The Drug Effectiveness Review Project, composed of 15 organizations including 14 state Medicaid agencies and the Canadian Agency for Drugs and Technology in Health, commissioned and funded for this report. These organizations selected the topic of the report and had input into its Key Questions. The content and conclusions of the report were entirely determined by the Evidence-based Practice Center researchers. The authors of this report have no financial interest in any company that makes or distributes the products reviewed in this report.

Suggested citation:

Smith MEB, Lee NJ, Haney E, Carson S. Drug class review: HMG-CoA reductase inhibitors (statins). Update 5. http://www.ohsu.edu/drugeffectiveness/reports/final.cfm

This report reviews information about the comparative effectiveness and safety of drugs within a pharmaceutical class. The report is neither a usage guideline nor an endorsement or recommendation of any drug, use, or approach. Oregon Health & Science University does not endorse any guideline or recommendation developed by users of this report.