title: Review of side-effect profile of combination ezetimibe and statin therapy in randomized clinical trials.
abstract: Effective treatment to achieve target lipid parameters in high-risk patients may require combination drug therapies. Concerns regarding risks associated with such combination therapies may limit their use. A systematic overview of randomized controlled trials to assess risks associated with combination statin and ezetimibe therapy was performed. Eighteen trials were identified, including 14,471 patients. Follow-up ranged from 6 to 48 weeks. Compared with statin monotherapy, combination therapy did not result in significant absolute increases in risks of myalgias (risk difference -0.033, 95% confidence interval [CI] -0.06 to -0.01), creatine kinase increases (risk difference 0.011, 95% CI -0.02 to 0.04), rhabdomyolysis (risk difference -0.003, 95% CI -0.01 to 0.004), transaminase increases (risk difference -0.003, 95% CI -0.01 to 0.005), gastrointestinal adverse events (risk difference 0.005, 95% CI -0.03 to 0.04), or discontinuations because of an adverse event (risk difference -0.005, 95% CI -0.03 to 0.02). In conclusion, based on available randomized trials, the addition of ezetimibe to statin therapy did not increase the risk of myalgias, creatine kinase increases, rhabdomyolysis, transaminase increases, gastrointestinal adverse events, or discontinuations because of an adverse event. Additional trials are necessary to ensure that results of clinical trials are consistent with routine clinical practice, particularly in older patients with more co-morbid conditions and patients on higher statin doses.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Kashani
authors.forename: Tamer
authors.initials: T
authors.lastname: Sallam
authors.forename: Swarna
authors.initials: S
authors.lastname: Bheemreddy
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: JoAnne M
authors.initials: JM
authors.lastname: Foody
mesh_terms: D000924:Anticholesteremic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001384:Azetidines / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D015994:Incidence; D008055:Lipids / Q000097:blood; D009135:Muscular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D000069438:Ezetimibe