Statin-fibrate combination therapy

BACKGROUND: Precautionary warnings for severe myopathy and rhabdomyolysis f rom 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 c linicians who care for patients with refractory mixed hyperlipidemia are ne eded. OBJECTIVE: To provide recommendations for clinicians in the treatment of re fractory 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 in volving 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 demonstr ated 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 i ncreased age, female gender, renal or liver disease, diabetes, hypothyroidi sm, debilitated status, surgery, trauma, excessive alcohol intake, and heav y exercise, CONCLUSIONS. Combination therapy with a statin and fibrate offers significa nt therapeutic advantage for the treatment of severe or refractory mixed hy perlipidemia. Although such a combination does increase the risk of myopath y, with an incidence of approximately 0.12%, this small risk of myopathy ra rely outweighs the established morbidity and mortality benefits of achievin g lipid goals. Nevertheless, a higher incidence of myopathy has been report ed 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 m yopathy. Statin-fibrate combination therapy must be undertaken cautiously a nd only after careful risks-benefit analysis. Patient counseling on the ris ks and warning signs of myopathy is extremely important.