Torcetrapib
Adding torcetrapib to atorvastatin lowers lipoprotein(a) by 11 percent while modestly raising PCSK9, an ILLUMINATE biomarker substudy finds (J Clin Lipidol 2018)
Original title: Effect of atorvastatin, cholesterol ester transfer protein inhibition, and diabetes mellitus on circulating proprotein subtilisin kexin type 9 and lipoprotein(a) levels in patients at high cardiovascular risk
This substudy measured PCSK9 and lipoprotein(a) [Lp(a)] levels in plasma from ILLUMINATE trial patients with coronary heart disease and/or type 2 diabetes, all first titrated on atorvastatin before randomization to atorvastatin plus torcetrapib or atorvastatin plus placebo. At baseline, both PCSK9 and Lp(a) rose dose-dependently with atorvastatin dose, and patients with type 2 diabetes had higher PCSK9 (357 plus or minus 123 versus 338 plus or minus 115 ng/mL, p = .0012) and lower Lp(a) (28 plus or minus 32 versus 32 plus or minus 33 mg/dL, p = .0005) than those without. Torcetrapib treatment significantly raised PCSK9 by 3.7% (p = .005) and lowered Lp(a) by 11.1% (p < .0001), while placebo produced no significant change in either marker, showing that CETP inhibition with torcetrapib has small but measurable, offsetting effects on these two independent cardiovascular risk factors.
Original abstract
Background: Proprotein subtilisin kexin type 9 (PCSK9) and lipoprotein (a) [Lp(a)] levels are causative risk factors for coronary heart disease.
Objectives: The objective of the study was to determine the impact of lipid-lowering treatments on circulating PCSK9 and Lp(a).
Methods: We measured PCSK9 and Lp(a) levels in plasma samples from Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events trial patients with coronary heart disease and/or type II diabetes (T2D) mellitus. Patients received atorvastatin, which was titrated (10, 20, 40, or 80 mg/d) to achieve low-density lipoprotein cholesterol levels <100 mg/dL (baseline) and were subsequently randomized either to atorvastatin + torcetrapib, a cholesterol ester transfer protein inhibitor, or to atorvastatin + placebo.
Results: At baseline, both plasma PCSK9 and Lp(a) were dose-dependently increased with increasing atorvastatin doses. Compared with patients without T2D, those with T2D had higher PCSK9 (357 ± 123 vs 338 ± 115 ng/mL, P = .0012) and lower Lp(a) levels (28 ± 32 vs 32 ± 33 mg/dL, P = .0005). Plasma PCSK9 levels significantly increased in patients treated with torcetrapib (+13.1 ± 125.3 ng/mL [+3.7%], P = .005), but not in patients treated with placebo (+2.6 ± 127.9 ng/mL [+0.7%], P = .39). Plasma Lp(a) levels significantly decreased in patients treated with torcetrapib (-3.4 ± 10.7 mg/dL [-11.1%], P < .0001), but not in patients treated with placebo (+0.3 ± 9.4 mg/dL [+0.1%], P = .92).
Conclusion: In patients at high cardiovascular disease risk, PCSK9 and Lp(a) are positively and dose-dependently correlated with atorvastatin dosage, whereas the presence of T2D is associated with higher PCSK9 but lower Lp(a) levels. Cholesterol ester transfer protein inhibition with torcetrapib slightly increases PCSK9 levels and decreases Lp(a) levels.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.