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This highlights a critical unmet need for additional lipid\u2010lowering therapies that are not only efficacious and orally administered, but also demonstrate durable safety and cardiovascular benefits. CETP (cholesteryl ester transfer protein) inhibition alters lipid metabolism by preventing the transfer of cholesteryl esters from high\u2010density lipoprotein to apolipoprotein B\u2013containing lipoproteins, thereby reducing atherogenic cholesterol burden. CETP inhibitors have had \u00a0a challenging development history due to off\u2010target effects observed in early compounds like torcetrapib. However, obicetrapib is a highly selective and hydrophilic CETP inhibitor that heralds a promising new generation of drugs with robust lipid\u2010lowering capabilities and a favorable safety profile. This review presents a comprehensive overview of obicetrapib's mechanism of action, its pharmacokinetic and pharmacodynamic profiles, and a detailed critical assessment of its clinical development through various pivotal trials including TULIP (TA\u20108995: Its Use in Patients With Mild Dyslipidemia), ROSE (Trial Evaluating Obicetrapib in Combination With Ezetimibe), ROSE2 (Phase 2b ROSE Trial Evaluating Obicetrapib in Combination With Ezetimibe), BROADWAY (Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid\u2010Modifying Therapies), BROOKLYN (Obicetrapib on Top of Maximum Tolerated Lipid\u2010Modifying Therapies, TANDEM (Study of Obicetrapib and Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid\u2010Modifying Therapies), and the ongoing PREVAIL (Cardiovascular Outcome Study to Evaluate the Effect of Obicetrapib in Patients With Cardiovascular Disease) cardiovascular outcomes trial. We compare the efficacy, safety, and tolerability of obicetrapib against prevailing treatment options, positioning it as a potential oral adjunct to maximally tolerated lipid\u2010lowering regimens in the current lipid management landscape.<\/jats:p>","DOI":"10.1161\/jaha.125.047676","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:38:56Z","timestamp":1776850736000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["From Failure to Promise: Obicetrapib and the Renaissance of Cholesteryl Ester Transfer Protein Inhibition in Atherosclerotic Cardiovascular Disease"],"prefix":"10.1161","volume":"15","author":[{"given":"Sudesh","family":"Prajapathi","sequence":"first","affiliation":[{"name":"All India Institute of Medical Sciences","place":["Bhopal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9378-6505","authenticated-orcid":false,"given":"Kunal","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Himachal Heart Institute","place":["Mandi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1244-7446","authenticated-orcid":false,"given":"Aditi","family":"Mohta","sequence":"additional","affiliation":[{"name":"People\u2019s College of Medical Sciences & Research Centre, People\u2019s University","place":["Bhopal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2360-7580","authenticated-orcid":false,"given":"Akshyaya","family":"Pradhan","sequence":"additional","affiliation":[{"name":"King George\u2019s Medical University","place":["Lucknow, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz455"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.11.003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd12080300"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2415820"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-024-01231-5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-023-01184-1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706628"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.790733"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1206797"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609581"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23169417"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.10.072"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706444"},{"key":"e_1_3_2_15_2","unstructured":"Merck Announces Results of REVEAL outcomes study of anacetrapib investigational medicine for cardiovascular disease. 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