Statin-fibrate combination therapy

BACKGROUND: Precautionary warnings for severe myopathy and rhabdomyolysis from the coadministration of statins and fibrates have been well publicized. However, a recent cerivastatin labeling change made the combined use with fibric acid derivatives a contraindication. Practical recommendations for clinicians who care for patients with refractory mixed hyperlipidemia are needed. OBJECTIVE: To provide recommendations for clinicians in the treatment of refractory mixed hyperlipidemia. DATA SOURCES: A comprehensive MEDLINE (1966-July 2000) and bibliographic search was performed. DATA SYNTHESIS: Thirty-six published clinical trials and 29 case reports involving combination therapy with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and fibric acid derivatives regarding the occurrence of rhabdomyolysis or myopathy were reviewed. The literature review demonstrated that combination therapy with a statin and fibrate increases the risk of muscle damage, with an incidence of 0.12%. Risk factors that predispose patients to myopathy caused by combination statin-fibrate therapy include increased age, female gender, renal or liver disease, diabetes, hypothyroidism, debilitated status, surgery, trauma, excessive alcohol intake, and heavy exercise. CONCLUSIONS: Combination therapy with a statin and fibrate offers significant therapeutic advantage for the treatment of severe or refractory mixed hyperlipidemia. Although such a combination does increase the risk of myopathy, with an incidence of approximately 0.12%, this small risk of myopathy rarely outweighs the established morbidity and mortality benefits of achieving lipid goals. Nevertheless, a higher incidence of myopathy has been reported with statin monotherapy. When monotherapy with a statin fails to control mixed hyperlipidemia, combination therapy may be considered. Niacin may be added before a fibrate is considered, as it appears to have less risk of myopathy. Statin-fibrate combination therapy must be undertaken cautiously and only after careful risk-benefit analysis. Patient counseling on the risks and warning signs of myopathy is extremely important.

This article has been cited by other articles:

				K. K. Koh, P. C. Oh, and M. J. Quon Does reversal of oxidative stress and inflammation provide vascular protection? Cardiovasc Res, March 1, 2009; 81(4): 649 - 659. [Abstract] [Full Text] [PDF]

				B. C.H. Kwan, F. Kronenberg, S. Beddhu, and A. K. Cheung Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1246 - 1261. [Full Text] [PDF]

				H. Akoglu, R. Yilmaz, A. Kirkpantur, M. Arici, B. Altun, and C. Turgan Combined Organ Failure with Combination Antihyperlipidemic Treatment: A Case of Hepatic Injury and Acute Renal Failure Ann. Pharmacother., January 1, 2007; 41(1): 143 - 147. [Abstract] [Full Text] [PDF]

				N. Shibata, K.-i. Jishage, M. Arita, M. Watanabe, Y. Kawase, K. Nishikawa, Y. Natori, H. Inoue, H. Shimano, N. Yamada, et al. Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis FASEB J, December 1, 2006; 20(14): 2642 - 2644. [Abstract] [Full Text] [PDF]

				G D Kolovou, K K Anagnostopoulou, and D V Cokkinos Pathophysiology of dyslipidaemia in the metabolic syndrome Postgrad. Med. J., June 1, 2005; 81(956): 358 - 366. [Abstract] [Full Text] [PDF]

				M. Farnier, M. W. Freeman, G. Macdonell, I. Perevozskaya, M. J. Davies, Y. B. Mitchel, B. Gumbiner, and for the Ezetimibe Study Group Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia Eur. Heart J., May 1, 2005; 26(9): 897 - 905. [Abstract] [Full Text] [PDF]

				D. J. Graham, J. A. Staffa, D. Shatin, S. E. Andrade, S. D. Schech, L. La Grenade, J. H. Gurwitz, K. A. Chan, M. J. Goodman, and R. Platt Incidence of Hospitalized Rhabdomyolysis in Patients Treated With Lipid-Lowering Drugs JAMA, December 1, 2004; 292(21): 2585 - 2590. [Abstract] [Full Text] [PDF]

				B. M. Psaty, C. D. Furberg, W. A. Ray, and N. S. Weiss Potential for Conflict of Interest in the Evaluation of Suspected Adverse Drug Reactions: Use of Cerivastatin and Risk of Rhabdomyolysis JAMA, December 1, 2004; 292(21): 2622 - 2631. [Abstract] [Full Text] [PDF]

				E. A. Meagher Addressing Cardiovascular Disease in Women: Focus on Dyslipidemia J Am Board Fam Med, November 1, 2004; 17(6): 424 - 437. [Abstract] [Full Text] [PDF]

				B. Brunmair, A. Lest, K. Staniek, F. Gras, N. Scharf, M. Roden, H. Nohl, W. Waldhausl, and C. Furnsinn Fenofibrate Impairs Rat Mitochondrial Function by Inhibition of Respiratory Complex I J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 109 - 114. [Abstract] [Full Text] [PDF]

				S. Bellosta, R. Paoletti, and A. Corsini Safety of Statins: Focus on Clinical Pharmacokinetics and Drug Interactions Circulation, June 15, 2004; 109(23_suppl_1): III-50 - III-57. [Abstract] [Full Text]

				L. Roten, R. A Schoenenberger, S. Krahenbuhl, and R. G Schlienger Rhabdomyolysis in Association with Simvastatin and Amiodarone Ann. Pharmacother., June 1, 2004; 38(6): 978 - 981. [Abstract] [Full Text] [PDF]

				J. McKenney New Perspectives on the Use of Niacin in the Treatment of Lipid Disorders Arch Intern Med, April 12, 2004; 164(7): 697 - 705. [Abstract] [Full Text] [PDF]

				R. Gadsby Review: Diabetic dyslipidaemia -- the case for using statins The British Journal of Diabetes & Vascular Disease, November 1, 2003; 3(6): 402 - 407. [Abstract] [PDF]

				C. M. Ballantyne and M. H. Davidson Possible Differences Between Fibrates in Pharmacokinetic Interactions With Statins Arch Intern Med, October 27, 2003; 163(19): 2394 - 2395. [Full Text] [PDF]

				A. Shaukat, M. Benekli, G. D Vladutiu, J. L Slack, M. Wetzler, and M. R Baer Simvastatin-Fluconazole Causing Rhabdomyolysis Ann. Pharmacother., July 1, 2003; 37(7): 1032 - 1035. [Abstract] [Full Text] [PDF]

				M. Evans, A. Roberts, and A. Rees Pharmacological management of hyperlipidaemia The British Journal of Diabetes & Vascular Disease, May 1, 2003; 3(3): 204 - 210. [Abstract] [PDF]

				P. D. Thompson, P. Clarkson, and R. H. Karas Statin-Associated Myopathy JAMA, April 2, 2003; 289(13): 1681 - 1690. [Abstract] [Full Text] [PDF]

				A. M. Gotto Jr Safety and Statin Therapy: Reconsidering the Risks and Benefits Arch Intern Med, March 24, 2003; 163(6): 657 - 659. [Full Text] [PDF]

				C. M. Ballantyne, A. Corsini, M. H. Davidson, H. Holdaas, T. A. Jacobson, E. Leitersdorf, W. Marz, J. P. D. Reckless, and E. A. Stein Risk for Myopathy With Statin Therapy in High-Risk Patients Arch Intern Med, March 10, 2003; 163(5): 553 - 564. [Abstract] [Full Text] [PDF]

				T. Prueksaritanont, C. Tang, Y. Qiu, L. Mu, R. Subramanian, and J. H. Lin Effects of Fibrates on Metabolism of Statins in Human Hepatocytes Drug Metab. Dispos., November 1, 2002; 30(11): 1280 - 1287. [Abstract] [Full Text] [PDF]

				T. Prueksaritanont, J. J. Zhao, B. Ma, B. A. Roadcap, C. Tang, Y. Qiu, L. Liu, J. H. Lin, P. G. Pearson, and T. A. Baillie Mechanistic Studies on Metabolic Interactions between Gemfibrozil and Statins J. Pharmacol. Exp. Ther., June 1, 2002; 301(3): 1042 - 1051. [Abstract] [Full Text] [PDF]