Comparison of the safety of statin monotherapy and coadministration with fenofibrate in patients with mixed hyperlipidemia a meta analysis
Objective: To compare adverse events of statin monotherapy and combination therapy of statin and fenofibrate. Methods: We searched the online databases of PUBMED and EMBASE for high quality randomized controlled trials (RCTs) Interested outcomes included discontinuation because of any adverse event, any adverse event, serious adverse events, drug related adverse events, increase in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) 3 times upper limit of normal (ULN) increase in creatine kinase (CK) 5 times ULN, increase in creatinine 50% and above ULN. As the incidence of adverse events was dichotomous, odds ratios (ORs) were calculated for each included trial with a fixed effects or random effects model depending on the heterogeneity of the studies. Results: Twelve RCTs covering 5398 participants were included in this meta analysis. Our results revealed that combination therapy was associated with a significantly higher discontinuation because of any adverse event compared with statin monotherapy (P 0.00001) but there were no significant difference in any adverse event (P 0.54) serious adverse events (P 0.55) and drug related adverse events (P 0.39) Fenofibrate plus statin did not result in a greater risk of muscle related adverse events than monotherapy (P 0.79) However, there were more hepatic enzyme elevation related adverse events (P 0.0006) and plasma creatinine elevation related adverse events (P 0.0002) in coadministration group than monotherapy group. Conclusions: The pooled evidence showed that combination therapy of statin and fenofibrate is associated with a higher incidence of hepatic and renal abnormality compared with statin monotherapy. Fenofibrate should be used carefully in patients with liver and renal impairment, and function of liver and kidney should be monitored closely within the combination therapy.