title: Effects of add-on lipid-modifying therapy on top of background statin treatment on major cardiovascular events: A meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  In patients at high risk of atherosclerotic cardiovascular diseases (ASCVDs), residual cardiovascular risk persists despite the achievement of target LDL cholesterol levels with statin therapy. It is still unclear whether adding lipid-modifying agent to statin treatment can further improve clinical outcomes.
  
  
  METHODS
  Randomized controlled trials (RCTs) in terms of adding lipid-modifying agent to statin versus statin monotherapy in patients at high risk of ASCVD were identified by electronic and manual searches. Results were expressed as relative risk (RR) with 95% confidence intervals (CIs).
  
  
  RESULTS
  Eleven RCTs with 109,244 patients were included in this meta-analysis. Overall, the incidences of major adverse cardiovascular events (MACEs) were 9.70% in the statin combination groups and 9.92% in the statin monotherapy groups. No significant difference was observed in the risk of MACEs either in overall (RR 0.99, 95% CI 0.93-1.05, P=0.76) or subgroup analysis (CETP inhibitor: RR 1.07, 95% CI 0.93-1.23, P=0.37; niacin: RR 1.03, 95% CI 0.85-1.25, P=0.79; n-3 fatty acid: RR 0.98, 95% CI 0.88-1.09, P=0.70; fenofibrate: RR 0.93, 95% CI 0.80-1.09, P=0.38), with the exception of the statin/ezetimibe combination subgroup (RR 0.92, 95% CI 0.87-0.97, P=0.004). Adding lipid-modifying agent to statin significantly increased liver injury risk. Adding ezetimibe to statin did not alter side effect profile.
  
  
  CONCLUSIONS
  Adding niacin, CETP inhibitors, n-3 fatty acid or fibrates to statin therapy has all failed to achieve a clinical benefit. Adding ezetimibe to statin therapy further lowers LDL-cholesterol safely and translates into a clinical benefit in patients at high risk of ASCVD.
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Electrophysiology and Arrhythmia of Guangdong Province, Guangzhou, China.
authors.forename: Chi-kin
authors.initials: CK
authors.lastname: Ip
authors.affiliation: Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Jin
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Electrophysiology and Arrhythmia of Guangdong Province, Guangzhou, China; Shenzhen Sun Yixian Cardiovascular Hospital, Shenzhen 518001,China.
authors.forename: Jia-jia
authors.initials: JJ
authors.lastname: Gao
authors.affiliation: Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou 215000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Electrophysiology and Arrhythmia of Guangdong Province, Guangzhou, China. Electronic address: dr.wangjf@hotmail.com.
authors.forename: Jing-feng
authors.initials: JF
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Electrophysiology and Arrhythmia of Guangdong Province, Guangzhou, China. Electronic address: dr.dfengg@hotmail.com.
authors.forename: Deng-feng
authors.initials: DF
authors.lastname: Geng
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids
keywords: Cardiovascular events; Cholesteryl ester transfer protein inhibitor; Ezetimibe; Fibrate; Niacin; Statin; n−3 fatty acid