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Christie M. Ballantyne, MD; Alberto Corsini, PhD; Michael H. Davidson, MD; Hallvard Holdaas, MD; Terry A. Jacobson, MD; Eran Leitersdorf, MD; Winfried März, MD; John P. D. Reckless, MD; Evan A. Stein, MD

Arch Intern Med. 2003;163:553-564.

Emerging data suggest that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) offer important benefits for the large population of individuals at high risk for coronary heart disease. This population encompasses a sizable portion of individuals who are also at high risk for drug-drug interactions due to their need for multiple medications. In general, statins are associated with a very small risk for myopathy (which may progress to fatal or nonfatal rhabdomyolysis); however, the potential for drug-drug interactions is known to increase this risk in specific high-risk groups. The incidence of myopathy associated with statin therapy is dose related and is increased when statins are used in combination with agents that share common metabolic pathways. Of particular concern is the potential for interactions with other lipid-lowering agents such as fibrates and niacin (nicotinic acid), which may be used in patients with mixed lipidemia, and with immunosuppressive agents, such as cyclosporine, which are commonly used in patients after transplantation. Clinicians should be alert to the potential for drug-drug interactions to minimize the risk of myopathy during long-term statin therapy in patients at high risk for coronary heart disease.

From Baylor College of Medicine, Houston, Tex (Dr Ballantyne); Department of Pharmacological Sciences, University of Milan, Milan, Italy (Dr Corsini); Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill (Dr Davidson); National Hospital, University of Oslo, Oslo, Norway (Dr Holdaas); Emory University School of Medicine, Atlanta, Ga (Dr Jacobson); Hadassah University Hospital, Jerusalem, Israel (Dr Leitersdorf); Karl Franzens University, Graz, Austria (Dr März); Royal United Hospital, Bath, England (Dr Reckless); and Medical Research Laboratories International, Highland Heights, Ky (Dr Stein). Dr Ballantyne has served as a consultant for Reliant, Merck & Co Inc, Novartis, Pfizer Inc, and AstraZeneca; participated on the speaker's bureau for Reliant, Merck & Co Inc, Novartis, Pfizer Inc, AstraZeneca, Schering Plough, KOS Pharmaceuticals Inc, and Bristol-Myers Squibb; and received grant/research support from Reliant, Merck & Co Inc, Novartis, Pfizer Inc, AstraZeneca, and Schering Plough. Dr Davidson has served as a consultant for AstraZeneca and Reliant; participated on the speaker's bureau for Merck & Co Inc, Pfizer Inc, Novartis, AstraZeneca, and KOS Pharmaceuticals Inc; received grant/research support from Merck & Co Inc, Pfizer Inc, AstraZeneca, Bristol-Myers Squibb, and KOS Pharmaceuticals Inc; and received an honorarium from Merck & Co Inc, Pfizer Inc, Pharmacia, Novartis, AstraZeneca, Wyeth, and KOS Pharmaceuticals Inc. Dr Leitersdorf has participated in a meeting on statin safety sponsored by Novartis. Dr Stein has served as a consultant and funded researcher and participated on the speaker's bureau for Novartis and Reliant.

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