Meta-analysis of 12 trials finds CETP inhibitors raise HDL-c by 20.5 mg/dL and lower LDL-c by 17.1 mg/dL, with a blood-pressure signal from torcetrapib (PLoS One 2013)

Original title: Cholesteryl ester transfer protein inhibitors in the treatment of dyslipidemia: a systematic review and meta-analysis

PLoS One · 1 January 2013 · 7

Li C, Zhang W, Zhou F, Chen C, Zhou L, Li Y, Liu L, Pei F, Luo H, Hu Z, Cai J, Zeng C

This systematic review and meta-analysis of double-blind randomized controlled trials assessed the efficacy and safety of cholesteryl ester transfer protein (CETP) inhibitors, alone or combined with statins, for dyslipidemia. Of 503 studies identified, 14 met inclusion criteria and 12 were meta-analyzed. CETP inhibitors significantly increased HDL cholesterol (n=2826, mean difference 20.47 mg/dL, 95% CI, 19.80 to 21.15, p<0.00001) and modestly increased total cholesterol (n=3423, mean difference 3.57, 95% CI, 1.69 to 5.44, p=0.0002), while reducing triglycerides (n=3739, mean difference -10.47, 95% CI, -11.91 to -9.03, p<0.00001) and LDL cholesterol (n=3159, mean difference -17.12, 95% CI, -18.87 to -15.36, p<0.00001), with effects varying across the four available CETP inhibitors. CETP inhibitor therapy did not increase overall adverse events versus control, but slightly raised systolic (mean difference 2.73 mmHg) and diastolic (mean difference 1.16 mmHg) blood pressure, an effect mainly attributed to the torcetrapib subgroup. The authors conclude CETP inhibitors improve lipid profiles with acceptable safety, though the blood-pressure signal warrants further study.

Original 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.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.