Xue H, Zhang M, Liu J, Wang J, Ren G. Structure-based mechanism and inhibition of cholesteryl ester transfer protein. Curr Atheroscler Rep. 2023;25:155–66. https://doi.org/10.1007/s11883-023-01087-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kurasawa T, Yokoyama S, Miyake Y, Yamamura T, Yamamoto A. Rate of cholesteryl ester transfer between high and low density lipoproteins in human serum and a case with decreased transfer rate in association with hyperalphalipoproteinemia. J Biochem. 1985;98:1499–508. https://doi.org/10.1093/oxfordjournals.jbchem.a135418.

Article  CAS  PubMed  Google Scholar 

Koizumi J, Mabuchi H, Yoshimura A, Michishita I, Takeda M, Itoh H, et al. Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia. Atherosclerosis. 1985;58:175–86. https://doi.org/10.1016/0021-9150(85)90064-4.

Article  CAS  PubMed  Google Scholar 

Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J, Takata K, et al. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med. 1990;323:1234–8. https://doi.org/10.1056/NEJM199011013231803.

Article  CAS  PubMed  Google Scholar 

Nagano M, Yamashita S, Hirano K, Takano M, Maruyama T, Ishihara M, et al. Molecular mechanisms of cholesteryl ester transfer protein deficiency in Japanese. J Atheroscler Thromb. 2004;11:110–21. https://doi.org/10.5551/jat.11.110.

Article  CAS  PubMed  Google Scholar 

Kannel WB. High-density lipoproteins: epidemiologic profile and risks of coronary artery disease. Am J Cardiol. 1983;52:9B-12B. https://doi.org/10.1016/0002-9149(83)90649-5.

Article  CAS  PubMed  Google Scholar 

Castelli WP. Cholesterol and lipids in the risk of coronary artery disease--the Framingham Heart Study. Can J Cardiol. 1988;4 Suppl A:5A-10A. https://www.ncbi.nlm.nih.gov/pubmed/3179802. Accessed 13 Aug 2023.

Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;79:8–15. https://doi.org/10.1161/01.cir.79.1.8.

Article  CAS  PubMed  Google Scholar 

Assmann G, Schulte H, von Eckardstein A, Huang Y. High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis. 1996;124(Suppl):S11-20. https://doi.org/10.1016/0021-9150(96)05852-2.

Article  CAS  PubMed  Google Scholar 

Emerging Risk Factors C, Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302:1993–2000. https://doi.org/10.1001/jama.2009.1619.

Ouimet M, Barrett TJ, Fisher EA. HDL and reverse cholesterol transport. Circ Res. 2019;124:1505–18. https://doi.org/10.1161/CIRCRESAHA.119.312617.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Endo Y, Fujita M, Ikewaki K. HDL functions-current status and future perspectives. Biomolecules. 2023;13(1):105. https://doi.org/10.3390/biom13010105.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aim-High Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–67. https://doi.org/10.1056/NEJMoa1107579.

Hps Thrive Collaborative Group, Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371:203–12. https://doi.org/10.1056/NEJMoa1300955.

D’Andrea E, Hey SP, Ramirez CL, Kesselheim AS. Assessment of the role of niacin in managing cardiovascular disease outcomes: a systematic review and meta-analysis. JAMA Netw Open. 2019;2: e192224. https://doi.org/10.1001/jamanetworkopen.2019.2224.

Article  PubMed  PubMed Central  Google Scholar 

Riaz H, Khan SU, Rahman H, Shah NP, Kaluski E, Lincoff AM, et al. Effects of high-density lipoprotein targeting treatments on cardiovascular outcomes: a systematic review and meta-analysis. Eur J Prev Cardiol. 2019;26:533–43. https://doi.org/10.1177/2047487318816495.

Article  PubMed  Google Scholar 

Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375:1875–84. https://doi.org/10.1016/S0140-6736(10)60656-3.

Article  CAS  PubMed  Google Scholar 

Wang D, Liu B, Tao W, Hao Z, Liu M. Fibrates for secondary prevention of cardiovascular disease and stroke. Cochrane Database Syst Rev. 2015;2015:CD009580. https://doi.org/10.1002/14651858.CD009580.pub2.

Jakob T, Nordmann AJ, Schandelmaier S, Ferreira-Gonzalez I, Briel M. Fibrates for primary prevention of cardiovascular disease events. Cochrane Database Syst Rev. 2016;11:CD009753. https://doi.org/10.1002/14651858.CD009753.pub2.

Kim NH, Kim SG. Fibrates revisited: potential role in cardiovascular risk reduction. Diabetes Metab J. 2020;44:213–21. https://doi.org/10.4093/dmj.2020.0001.

Article  PubMed  PubMed Central  Google Scholar 

Kjeldsen EW, Thomassen JQ, Frikke-Schmidt R. HDL cholesterol concentrations and risk of atherosclerotic cardiovascular disease - insights from randomized clinical trials and human genetics. Biochim Biophys Acta Mol Cell Biol Lipids. 2022;1867: 159063. https://doi.org/10.1016/j.bbalip.2021.159063.

Article  CAS  PubMed  Google Scholar 

Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22. https://doi.org/10.1056/NEJMoa0706628.

Article  CAS  PubMed  Google Scholar 

Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089–99. https://doi.org/10.1056/NEJMoa1206797.

Article  CAS  PubMed  Google Scholar 

Kosmas CE, DeJesus E, Rosario D, Vittorio TJ. CETP inhibition: past failures and future hopes. Clin Med Insights Cardiol. 2016;10:37–42. https://doi.org/10.4137/CMC.S32667.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lincoff AM, Nicholls SJ, Riesmeyer JS, Barter PJ, Brewer HB, Fox KAA, et al. Evacetrapib and cardiovascular outcomes in high-risk vascular disease. N Engl J Med. 2017;376:1933–42. https://doi.org/10.1056/NEJMoa1609581.

Article  PubMed  Google Scholar 

Tall AR, Rader DJ. Trials and tribulations of CETP inhibitors. Circ Res. 2018;122:106–12. https://doi.org/10.1161/CIRCRESAHA.117.311978.

Article  CAS  PubMed  Google Scholar 

Schmidt AF, Hunt NB, Gordillo-Maranon M, Charoen P, Drenos F, Kivimaki M, et al. Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease. Nat Commun. 2021;12:5640. https://doi.org/10.1038/s41467-021-25703-3.

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Hps Timi Reveal Collaborative Group, Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, et al. Effects of anacetrapib in patients with atherosclerotic vascular disease. N Engl J Med. 2017;377:1217–27. https://doi.org/10.1056/NEJMoa1706444.

• Nelson AJ, Sniderman AD, Ditmarsch M, Dicklin MR, Nicholls SJ, Davidson MH, et al. Cholesteryl ester transfer protein inhibition reduces major adverse cardiovascular events by lowering apolipoprotein B levels. Int J Mol Sci. 2022;23. https://doi.org/10.3390/ijms23169417. Review paper describing the evidence for a reduction in cardiovascular disease risk directly proportional to reductions in LDL cholesterol and Apo B levels with CETP inhibitor treatments.

Nurmohamed NS, Ditmarsch M, Kastelein JJP. Cholesteryl ester transfer protein inhibitors: from high-density lipoprotein cholesterol to low-density lipoprotein cholesterol lowering agents? Cardiovasc Res. 2022;118:2919–31. https://doi.org/10.1093/cvr/cvab350.

Article  CAS  PubMed  Google Scholar 

Merck News Release. Merck provides update on anacetrapib development program. In: Merck & Co, Inc. https://www.merck.com/news/merck-provides-update-on-anacetrapib-development-program/. Accessed 13 Aug 2023.

Krishna R, Gheyas F, Liu Y, Hagen DR, Walker B, Chawla A, et al. Chronic administration of anacetrapib is associated with accumulation in adipose and slow elimination. Clin Pharmacol Ther. 2017;102:832–40. https://doi.org/10.1002/cpt.700.

Article  CAS  PubMed  Google Scholar 

Lee JM, Lee YJ, Kwon NY, Ryu KH. Old target, but new drug: 2nd generation CETP inhibitor, CKD-508. Atherosclerosis. 2020;315:e108–281.

Article  Google Scholar 

Vachal P, Duffy JL, Campeau LC, Amin RP, Mitra K, Murphy BA, et al. Invention of MK-8262, a cholesteryl ester transfer protein (CETP) inhibitor backup to anacetrapib with best-in-class properties. J Med Chem. 2021;64:13215–58. https://doi.org/10.1021/acs.jmedchem.1c00959.

Article  CAS  PubMed  Google Scholar 

• Ballantyne CM, Ditmarsch M, Kastelein JJ, Nelson AJ, Kling D, Hsieh A, et al. Obicetrapib plus ezetimibe as an adjunct to high-intensity statin therapy: a randomized phase 2 trial. J Clin Lipidol. 2023. https://doi.org/10.1016/j.jacl.2023.05.098. Phase 2b randomized controlled trial showing obicetrapib plus ezetimibe on top of high-intensity statin therapy significantly reduced LDL-C, Apo B, and LDL particles.

NewAmsterdam Pharma. Evaluate the effect of obicetrapib in patients with HeFH on top of maximum tolerated lipid-modifying therapies (BROOKLYN). In: U.S. Department of Health and Human Services, National Institutes of Health, National LIbrary of Medicine, National Center for Biotechnology Information, ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT05425745. Accessed 13 Aug 2023.

NewAmsterdam Pharma. Randomized study to evaluate the effect of obicetrapib on top of maximum tolerated lipid-modifying therapies (BROADWAY). In: U.S. Department of Health and Human Services, National Institutes of Health, National LIbrary of Medicine, National Center for Biotechnology Information, ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT05142722. Accessed 13 Aug 2023.

NewAmsterdam Pharma. Cardiovascular outcome study to evaluate the effect of obicetrapib in patients with cardiovascular disease (PREVAIL). In: U.S. Department of Health and Human Services, National Institutes of Health, National LIbrary of Medicine, National Center for Biotechnology Information, ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT05202509. Accessed 13 Aug 2023.

Ford J, Lawson M, Fowler D, Maruyama N, Mito S, Tomiyasu K, et al. Tolerability, pharmacokinetics and pharmacodynamics of TA-8995, a selective cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Br J Clin Pharmacol. 2014;78:498–508. https://doi.org/10.1111/bcp.12380.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hovingh GK, Kastelein JJ, van Deventer SJ, Round P, Ford J, Saleheen D, et al. Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2015;386:452–60. https://doi.org/10.1016/S0140-6736(15)60158-1.

Article  CAS  PubMed  Google Scholar 

van Capelleveen JC, Kastelein JJ, Zwinderman AH, van Deventer SJ, Collins HL, Adelman SJ, et al. Effects of the cholesteryl ester transfer protein inhibitor, TA-8995, on cholesterol efflux capacity and high-density lipoprotein particle subclasses. J Clin Lipidol. 2016;10(1137–44): e3. https://doi.org/10.1016/j.jacl.2016.06.006.

Article