title: Cholesteryl ester transfer protein inhibitors in the treatment of dyslipidemia: a systematic review and meta-analysis.
abstract: Cholesteryl ester transfer protein (CETP) inhibitors are gaining substantial research interest for raising high density lipoprotein cholesterol levels. The aim of the research was to estimate the efficacy and safety of cholesteryl ester transfer protein inhibitors as novel lipid modifying drugs. Systematic searches of English literature for randomized controlled trials (RCT) were collected from MEDLINE, EBASE, CENTRAL and references listed in eligible studies. Two independent authors assessed the search results and only included the double-blind RCTs by using cholesteryl ester transfer protein inhibitors as exclusively or co-administrated with statin therapy irrespective of gender in enrolled adult subjects. Two independent authors extracted the data by using predefined data fields. Of 503 studies identified, 14 studies met the inclusion criteria, and 12 studies were included into the final meta-analysis. Our meta-analysis revealed that CETP inhibitors increased the HDL-c levels (n = 2826, p<0.00001, mean difference (MD) = 20.47, 95% CI [19.80 to 21.15]) and total cholesterol (n = 3423, p = 0.0002, MD = 3.57, 95%CI [1.69 to 5.44] to some extent combined with a reduction in triglyceride (n = 3739, p<0.00001, MD = -10.47, 95% CI [-11.91 to -9.03]) and LDL-c (n = 3159, p<0.00001, MD = -17.12, 95% CI [-18.87 to -15.36]) irrespective of mono-therapy or co-administration with statins. Subgroup analysis suggested that the lipid modifying effects varied according to the four currently available CETP inhibitors. CETP inhibitor therapy did not increase the adverse events when compared with control. However, we observed a slight increase in blood pressure (SBP, n = 2384, p<0.00001, MD = 2.73, 95% CI [2.14 to 3.31], DBP, n = 2384, p<0.00001, MD = 1.16, 95% CI [0.73 to 1.60]) after CETP inhibitor treatment, which were mainly ascribed to the torcetrapib treatment subgroup. CETP inhibitors therapy is associated with significant increase in HDL-c and decrease in triglyceride and LDL-c with satisfactory safety and tolerability in patients with dyslipidemia. However, the side-effect on blood pressure deserves more consideration in future studies.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, PR China ; Chongqing Institute of Cardiology, Chongqing, PR China.
authors.forename: Chuanwei
authors.initials: C
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Faying
authors.initials: F
authors.lastname: Zhou
authors.forename: Caiyu
authors.initials: C
authors.lastname: Chen
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Yafei
authors.initials: Y
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Pei
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.forename: Zhangxue
authors.initials: Z
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000577:Amides; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D004952:Esters; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000577:Amides; D000924:Anticholesteremic Agents; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004952:Esters; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D023303:Oxazolidinones; D011804:Quinolines; D013438:Sulfhydryl Compounds; D014280:Triglycerides; D001569:Benzodiazepines; C411602:dalcetrapib; C483909:torcetrapib; C568301:evacetrapib; D002784:Cholesterol; C530884:anacetrapib