J Lipid Atheroscler.  2018 Jun;7(1):12-20. 10.12997/jla.2018.7.1.12.

What Do We Get from Recent Statin and CETP Inhibitors Trials?

• Kim BJ

• KMID: 2416254
• DOI: http://doi.org/10.12997/jla.2018.7.1.12

Abstract

Recent clinical trials and meta-analyses have indicated that high-intensive statin treatment lowers low-density lipoprotein cholesterol (LDL-C) levels and reduces the risk of nonfatal cardiovascular (CV) events compared with moderate-intensity statin treatment. However, there are residual risks of CV events and safety concerns associated with high-intensity statin treatment. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) study showed that ezetimibe plus moderate-intensity statin therapy after acute coronary syndromes incrementally lowers LDL-C levels and improved CV outcomes compared with moderate-intensity statin therapy. However, despite the LDL-C-lowering effects, a substantial residual CV risk still remains, which includes other lipid abnormalities such as low high-density lipoprotein cholesterol (HDL-C). The most representative agents that primarily increase HDL-C are cholesteryl ester transfer protein (CETP) inhibitors. Until now, 4 CETP inhibitors, including torcetrapib, dalcetrapib, evacetrapib, and anacetrapib, have been introduced and all have significantly raised the HDL-C from 30% to 133%. However, the results for CV outcomes in clinical trials differed, based on the 4 agents. Torcetrapib increased the risk of CV events and total mortality in patients at high CV risk (ILLUMINATE trial). Dalcetrapib and evacetrapib did not result in lower rate of CV events in patients with recent acute coronary syndrome and high risk vascular disease, respectively (dal-OUTCOMES and ACCELERATE trials). However, anacetrapib significantly decreased the incidence of major coronary events in patients with atherosclerotic vascular disease (REVEAL trial). This topic summarizes the major results of recent statin and CETP inhibitor trials and provides framework to interpret and implement the trial results in real clinical practice.

Keyword

Dyslipidemia; Statins; Ezetimibe; Cholesterol ester transfer protein; Cholesteryl ester transfer protein inhibitor; High-density lipoprotein cholesterol

MeSH Terms

Acute Coronary Syndrome
Cholesterol
Cholesterol Ester Transfer Proteins
Dyslipidemias
Ezetimibe
Ezetimibe, Simvastatin Drug Combination
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors*
Incidence
Lipoproteins
Mortality
Vascular Diseases
Cholesterol
Cholesterol Ester Transfer Proteins
Ezetimibe
Ezetimibe, Simvastatin Drug Combination
Lipoproteins

Figure

• 

  Fig. 1 Putative mechanisms explaining the effect of CETP inhibitors on HDL-C and LDL-C. (A) decreased transfer CE in HDL into TRL; (B) decreased transfer CE in HDL into LDL; and (C) increased catabolism of LDL with increased uptake of LDL via hepatic LDL receptor. CETP; cholesteryl ester transfer protein, CE; cholesterol ester, HDL-C; high-density lipoprotein cholesterol, LDL-C; low-density lipoprotein cholesterol, TRL; triglyceride-rich lipoprotein, VLDL; very low-density lipoprotein, IDL; intermediate density lipoprotein.

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