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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Controlling Cholesterol With Combination Therapy


GOAL
To provide physicians with current information on managing dyslipidemia with combination therapy.

TARGET AUDIENCE
This activity is designed for cardiologists and primary care physicians.

LEARNING OBJECTIVES
After reading this issue, the participant should be able to:

  • Identify the type of patient who would be an ideal candidate for combination therapy.
  • Describe the drug combinations that are the most appropriate in terms of safety and practicality.
  • Explain the advantages/disadvantages of titrating patients with various risk factors.

ACCREDITATION STATEMENT
This activity has been planned and produced in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education. The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians. The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 hours in Category 1 credit toward the American Medical Association Physician's Recognition Award. Each physician should claim only those hours of credit that are actually spent on the educational activity. Credits are available until the expiration date of August 31, 2003.

This continuing education activity was produced under the supervision of Peter O. Kwiterovich, Jr., MD, Professor of Medicine and Pediatrics, Johns Hopkins University School of Medicine.

This program is supported by an unrestricted educational grant from Sankyo Pharma.

Publisher's Note and Disclaimer: The opinions expressed in this issue are those of the authors, presenters, and/or panelists and are not attributable to the publisher, editor, advisory board of Advanced Studies in Medicine, or The Johns Hopkins University School of Medicine or its Office of Continuing Medical Education. Clinical judgment must guide each professional in weighing the benefits of treatment against the risk of toxicity. Dosages, indications, and methods of use for products referred to in this issue are not necessarily the same as indicated in the package insert for the product and may reflect the clinical experience of the authors, presenters, and/or panelists or may be derived from the professional literature or other clinical sources. Consult complete prescribing information before administering.

Advanced Studies in Medicine (ISSN-1530-3004) is published by Galen Publishing, LLC, an HMG Company. P.O. Box 340, Somerville, NJ 08876. (908) 253-9001. Web site: www.galenpublishing.com. Copyright ©2001 by Galen Publishing, LLC. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. Bulk postage paid at Somerville, NJ Post Office and at additional mailing offices. Advanced Studies in Medicine is a registered trademark of The Healthcare Media Group, LLC. Printed on acid-free paper. BPA Membership applied for December 2000.

CHAIR

    Peter O. Kwiterovich, Jr., MD
    Professor of Medicine and Pediatrics
    Johns Hopkins University School of Medicine
    Director, Johns Hopkins University Lipid Clinic
    Chief, Lipid Research
    Johns Hopkins University Hospital
    Baltimore, Maryland
    • Dr. Kwiterovich reports receiving lecture and research support from Merck, Pfizer, and Parke- Davis; research support from AstraZeneca; research support from and serving on the advisory committee for Merck/Schering-Plough Singapore, Dupont, and KOS; lecture and research support from and serving on the advisory committee for Bayer and SmithKline; and serving on the advisory committee for Sankyo.

PARTICIPATING FACULTY

    Donald Hunninghake, MD
    Professor, Department of Medicine and Pharmacology
    Director, Heart Disease Prevention Clinic
    University of Minnesota Medical School
    Minneapolis, Minnesota
    • Dr. Hunninghake reports receiving research support from Merck, Bayer, Pfizer, KOS, Sankyo, Wyeth-Ayerst, TAP, and AstraZeneca; and honoraria from Pfizer, Sankyo, TAP, AstraZeneca, and Merck.

    Peter H. Jones, MD
    Associate Professor of Medicine Section of Atherosclerosis and Lipoprotein Research
    Baylor College of Medicine
    Houston, Texas
    • Dr. Jones reports receiving research support and honoraria from Pfizer and AstraZeneca; and research support from KOS and Bayer.

    James M. McKenney, PharmD
    Professor Emeritus
    Virginia Commonwealth University
    President and CEO
    National Clinical Research
    Richmond, Virginia
    • Dr. McKenney reports receiving lecture and research support and serving as a consultant to Pfizer and AstraZeneca; receiving lecture and research support from KOS, Bayer, and Novartis; receiving research support from SKB, Sankyo, Glaxo, and Schering-Plough; and receiving research support from and serving as a consultant to Merck.

    Xue-Qiao Zhao, MD
    Assistant Professor
    University of Washington Medical Center
    Cardiology Division
    • Dr. Zhao reports receiving research support from Pfizer, Merck, KOS, and Sankyo.

Advanced Studies in Medicine makes every effort to provide the reader with full disclosure information from major contributors. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts or other very brief summaries.

Dyslipidemia remains a major contributor to the annual burden of coronary heart disease (CHD), which currently causes 500,000 deaths and 1.1 million heart attacks each year in the United States. More than 70 million adult Americans have total cholesterol levels that exceed 200 mg/dL, and approximately 40 million have cholesterol levels greater than 240 mg/dL, the current definition of hypercholesterolemia.

Earlier this year, the third National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) released new recommendations for diagnosis and management of lipid disorders. In keeping with previous versions, the new clinical guidelines continue to define a high-risk cholesterol level as greater than 240 mg/dL. Other lipid-defined classifications also remain intact. The 2001 recommendations retain previous versions' focus on low-density lipoprotein (LDL) cholesterol as the primary target of therapy. Additionally, the new guidelines continue to emphasize the importance of dietary modification and exercise as key components of any strategy to achieve and maintain target lipid values.

However, ATP III embraces a more aggressive approach to the use of drug therapy. The number of individuals who qualify for drug treatment of dyslipidemia will triple, compared to ATP II. The new guidelines also introduce the category of "CHD risk equivalent," defined as a patient without CHD who nonetheless has a risk profile equivalent to that of a person who has a history of CHD or myocardial infarction. Patients with diabetes or renal insufficiency offer 2 examples of CHD risk equivalence.

For many dyslipidemic patients, the 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitors (statins) represent the treatment of choice. However, the decision-making process does not begin and end with the default selection of a statin. Evidence from clinical trials and clinical practice shows that a majority of dyslipidemic patients do not achieve target lipid levels. In many instances, even high-risk patients do not receive drug therapy. When drug therapy is prescribed, only a minority of patients reach lipid goals, as defined by the NCEP.

Multiple factors contribute to the failure to achieve recognized lipid goals with drug therapy. Many patients receive no more than a starting dose, which often is less than the dose that has proven effective in clinical trials. Drug therapy is frequently not accompanied by dietary modification, which remains an independent predictor of the likelihood of achieving defined lipid goals. Combination drug therapy receives scant attention in most physicians' treatment strategies.

For the most part, statins have proven to be exceptionally safe drugs, even at high doses. However, some patients clearly experience troubling side effects, such as myositis and liver enzyme elevations, which tend to occur most often with high-dose statin therapy.

As an alternative high-dose statin therapy, combination drug treatment offers an effective strategy that is generally safe and well tolerated. The most common combination strategy is to add a drug from another class to a statin. Bile acid resins and niacin are common add-on therapies to a statin. Combination therapy has some distinct advantages. In general, lower doses of each drug can be used, minimizing the risk of side effects. Additionally, combining a drug with a statin typically achieves an additional 10% reduction in LDL, whereas doubling the dose of a statin will result in about a 6% additional lowering of LDL.

Unfortunately, niacin and conventional bile acid resins are among the most troublesome lipid-lowering therapies with respect to side effects and tolerance. Niacin frequently can cause vasomotor symptoms that some patients find intolerable. The same is true of the gastrointestinal side effects of conventional bile acid resins. Recently, the nonsystemic, new-generation bile acid resin colesevelam has become available as an alternative for add-on therapy. The compound also represents an option as single-drug therapy for patients who have mild or moderate forms of dyslipidemia. In clinical trials, colesevelam has proven to be well tolerated when used as monotherapy or when added to existing statin therapy.

The review article, roundtable discussion, and case study that follow address current concepts and some of the key issues involved in the diagnosis and treatment of lipid disorders. The information also provides insights into ATP III and the new NCEP guidelines' implications for clinical practice. Several authorities in the field of dyslipidemia share their knowledge and experience from clinical practice, including views on how best to achieve lipid goals in specific types of patients and lipid disorders.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.