Anacetrapib 129 items
REVEAL, the only positive outcomes trial in the class, and the decision not to file.
Trials, agents, guidance
- Agent Anacetrapib
- Trial REVEAL
Studies
- REVEAL extended follow-up: the coronary benefit of anacetrapib grows over time, 12% overall, with no long-term safety signal (Eur Heart J 2022)
- REVEAL: anacetrapib cuts major coronary events by 9% in 30,449 patients already on intensive statin therapy (N Engl J Med 2017)
- Landmark NEJM safety trial shows anacetrapib avoids the cardiovascular harm of torcetrapib while doubling HDL cholesterol (N Engl J Med 2010)
- REVEAL, the largest ADCY9 pharmacogenetic study yet, finds no genotype interaction with the benefit of anacetrapib, unlike the dalcetrapib hypothesis (Circulation 2019)
- REALIZE phase 3 trial: anacetrapib cuts LDL-C by 39·7% versus placebo in familial hypercholesterolaemia over one year (Lancet 2015)
- First-in-class phase I trials show anacetrapib raises HDL-C by 129% and lowers LDL-C by 38% without raising blood pressure (Lancet 2007)
- Bayesian network meta-analysis of 84,134 patients ranks evacetrapib and anacetrapib best for cardiovascular outcomes among CETP inhibitors (Medicine 2026)
- Network meta-analysis of 2,937 patients: obicetrapib outperforms anacetrapib on LDL-C, HDL-C and overall adverse events (Daru 2026)
- Network meta-analysis of 33 RCTs in 120,292 adults: atorvastatin plus obicetrapib ranks best for LDL-C, rosuvastatin plus obicetrapib best for HDL-C (Clin Cardiol 2025)
- First meta-analysis of nine CETP-inhibitor RCTs finds a class-wide reduction in cardiovascular mortality and myocardial infarction (J Cardiovasc Dev Dis 2024)
- From raising HDL-C to lowering LDL-C: a review argues Mendelian randomisation and anacetrapib recast the whole CETP-inhibitor class (Cardiovasc Res 2022)
- CETP inhibition reduces major cardiovascular events through apoB lowering, a review argues, with obicetrapib cutting apoB by up to 30% (Int J Mol Sci 2022)
- Genetic and drug-based CETP inhibition preserves HDL and improves survival in sepsis, in humans and humanized mice (Circulation 2021)
- In obese CETP-transgenic mice, anacetrapib improved HDL function but drove fatty liver and insulin resistance, a clue to trials where two-thirds of patients were obese (Diabetes 2018)
- Meta-analysis of 34,781 patients confirms the lipid benefits of anacetrapib carry no excess hepatic or muscular risk (Postgrad Med 2018)
- Anacetrapib lowers lipoprotein(a) by cutting its production rate 41%, not by speeding its clearance (ATVB 2017)
- Phase 3 trial finds anacetrapib added to statins cuts LDL-C by 37% and more than doubles HDL-C, well tolerated over 24 weeks (Am J Cardiol 2017)
- Anacetrapib impairs endothelial function in CETP-transgenic mice despite raising HDL-C fivefold, while evacetrapib does not (Atherosclerosis 2017)
- Anacetrapib raises HDL apoA-I and plasma CETP levels by slowing their clearance rather than boosting their production (ATVB 2016)
- CETP inhibitors raise blood pressure through a CETP-independent, redox- and STAT3-dependent vascular contraction pathway (J Pharmacol Exp Ther 2016)
- Anacetrapib lowers LDL-ApoB by accelerating its clearance, not by slowing its production (J Clin Invest 2015)
- CETP inhibitors trigger aldosterone-producing enzymes in adipocytes through Nox-driven reactive oxygen species and STAT3 (J Pharmacol Exp Ther 2015)
- Anacetrapib dose-dependently shrinks atherosclerotic lesions by up to 92% and adds to the benefit of atorvastatin (Eur Heart J 2015)
- Two more years of anacetrapib in the DEFINE extension sustain a 39.9% LDL-C drop and 153.3% HDL-C rise with no new safety signals (J Cardiovasc Pharmacol Ther 2014)
- Medicinal chemistry paper describes the structure-activity work that led to the discovery of anacetrapib (J Med Chem 2011)
- Only dalcetrapib preserves pre-beta HDL formation and boosts fecal sterol excretion, unlike torcetrapib and anacetrapib (J Lipid Res 2010)
- Anacetrapib binds CETP reversibly while dalcetrapib binds covalently, explaining their different inhibitory kinetics (J Lipid Res 2010)
- Anacetrapib doubles HDL cholesterol and, unlike niacin, boosts cholesterol efflux per particle at high HDL levels (ATVB 2010)
- Adrenalectomy prevents the torcetrapib blood pressure rise, proving CETP inhibition itself is not the culprit (Br J Pharmacol 2008)
- Mouse mechanism study: CETP inhibition raises HDL, which blocks IL-1beta activation via SR-B1 and cuts endotoxaemia mortality (J Lipid Res 2025)
- Unlike anacetrapib, obicetrapib clears completely from the body and does not accumulate in fat, monkey and human data show (Pharmacol Res Perspect 2024)
- Anacetrapib reduces mortality from pneumococcal sepsis in mice by priming monocytes and speeding bacterial clearance (JCI Insight 2024)
- In REVEAL, new stroke, heart failure or cancer each cut quality of life and add thousands in hospital costs, but MI and coronary revascularisation alone do not (J Am Heart Assoc 2023)
- Dalcetrapib and anacetrapib generate large apoE-containing HDL particles that can bind the hepatic LDL receptor (J Lipid Res 2023)
- MK-8262 is invented as a best-in-class CETP inhibitor backup to anacetrapib after its 9% added cardiovascular risk reduction (J Med Chem 2021)
- Anacetrapib raises macrophage cholesterol efflux capacity in men, with the effect modified by haptoglobin genotype in diabetes (JAHA 2020)
- Meta-analysis of 62,431 patients across 11 RCTs finds CETP inhibitors do not reduce major adverse cardiovascular events (RR 0.97) (Cardiology 2020)
- An anacetrapib analog cuts CETP activity by 89% and reduces neointimal hyperplasia in bypassed rabbit veins by 38% (Sci Rep 2019)
- Anacetrapib parks itself in the lipid droplets of fat cells without needing active transport, explaining its long half-life and shelving (Drug Metab Dispos 2019)
- Unlike statins, anacetrapib lowers rather than raises new-onset diabetes risk on top of a coronary benefit, a review argues for a statin-plus-CETP-inhibitor combination (Atherosclerosis 2018)
- What the cetrapib trials taught us: torcetrapib, evacetrapib and anacetrapib all raised atherogenic apoproteins, muddying the HDL-raising story (Curr Opin Lipidol 2018)
- Were the benefits of REVEAL with anacetrapib really major? A critical evaluation says not significant in years one or two, and modest overall (Expert Opin Pharmacother 2018)
- The present therapeutic role of CETP inhibitors: REVEAL numbers, HDL-C +104%, LDL-C -18%, major coronary events RR 0.91, against three prior failures (Pharmacol Res 2018)
- A new piperidine-based CETP inhibitor retains potency in hypertriglyceridemic plasma where other CETP inhibitors lose efficacy (J Med Chem 2017)
- Inhibiting CETP with des-fluoro-anacetrapib cuts in-stent intimal area by 43% via a scavenger receptor-B1-dependent pathway (ATVB 2017)
- Trials and tribulations of CETP inhibitors: the REVEAL benefit traces to lower non-HDL-C, not higher HDL-C, plus a small diabetes reduction (Circ Res 2018)
- Anacetrapib, the new CETP inhibitor: raises large HDL2 and pre-beta HDL, lowers Lp(a) via ApoA production, and shows a hint of glucose benefit (Diseases 2017)
- Same drug, opposite effect: dalcetrapib raised HDL in rabbits but cut it 48% in monkeys, while anacetrapib behaved consistently across species (J Lipid Res 2017)
- Human phase 1 data confirm anacetrapib keeps accumulating in fat for a year while plasma levels plateau, explaining its long residence time (Clin Pharmacol Ther 2017)
- Anacetrapib lowers VLDL triglyceride only on a statin background, by boosting the catabolic rate of VLDL-TG (J Lipid Res 2017)
- In Japanese patients, adding anacetrapib to statins nearly doubles HDL-C and sustains lipid benefits through a 28-week extension (Atherosclerosis 2017)
- REVEAL trial design enrolled 30,449 patients to test whether anacetrapib lipid changes reduce cardiovascular events (Am Heart J 2017)
- Both 25 mg and 100 mg doses of anacetrapib substantially cut LDL-C and raise HDL-C on top of statin therapy (Am J Cardiol 2017)
- In Japanese patients with familial hypercholesterolaemia, anacetrapib cuts LDL-C by nearly 30% versus placebo in 12 weeks (Atherosclerosis 2016)
- White adipose tissue accumulates anacetrapib up to 40-fold, explaining its long elimination half-life in mice (Drug Metab Dispos 2016)
- A new non-steady-state tracer method shows anacetrapib blocks 97% of postprandial triglyceride flux into HDL (J Lipid Res 2016)
- Anacetrapib lowers VLDL/LDL cholesterol through both CETP inhibition and a separate PCSK9-lowering mechanism in mice (J Lipid Res 2015)
- Inhibiting CETP with des-fluoro-anacetrapib doubles capillary density in ischemic rabbit hindlimbs via SR-B1 and PI3K/Akt signaling (Int J Cardiol 2015)
- In vivo, anacetrapib promotes rather than blocks cholesteryl ester flux into large HDL, contradicting in vitro homotypic-transfer predictions (Eur J Pharmacol 2015)
- Modeling predicts a 550-day half-life for the tissue depot of anacetrapib, but no comparable accumulation for evacetrapib (J Clin Pharmacol 2015)
- Inhibiting CETP with des-fluoro-anacetrapib nearly doubles re-endothelialization after balloon injury in rabbit aortas (ATVB 2015)
- Atomistic simulations show anacetrapib lodges in the N-terminal tunnel of CETP to block cholesteryl ester diffusion (PLoS Comput Biol 2014)
- Anacetrapib reshapes LDL particle subfractions differently than atorvastatin, and neither drug reduces the smallest LDL particles (J Clin Lipidol 2015)
- At matched CETP inhibition, only anacetrapib boosts macrophage-to-feces cholesterol excretion in dyslipidemic hamsters (Eur J Pharmacol 2014)
- In rhesus macaques, anacetrapib reproduces the human lipid response and significantly lowers plasma PCSK9 (Eur J Pharmacol 2014)
- Even at 8 times the therapeutic dose, anacetrapib does not clinically prolong the QTcF interval (J Clin Pharmacol 2014)
- Anacetrapib lipid effects and detectable plasma drug persist for years after stopping treatment (Am J Cardiol 2014)
- In hamsters, anacetrapib raises preβ HDL and reverse cholesterol transport without affecting cholesterol absorption, unlike dalcetrapib (J Lipid Res 2013)
- Antisense CETP inhibition, unlike anacetrapib, boosts macrophage reverse cholesterol transport in CETP-transgenic mice (J Lipid Res 2013)
- Ten-arm dose-ranging trial in Japanese patients shows anacetrapib raises HDL-C up to 159% and adds to the LDL-lowering of atorvastatin (Atherosclerosis 2013)
- Anacetrapib-raised HDL retains its anti-inflammatory effect on endothelial cells (Biochim Biophys Acta 2013)
- The Friedewald formula underestimates LDL-C by 12 mg/dl after anacetrapib treatment, likely from VLDL-C overestimation (J Lipid Res 2013)
- DEFINE trial found anacetrapib safe through 76 weeks with no signal for the 25% event excess seen with a prior CETP inhibitor (Expert Rev Cardiovasc Ther 2012)
- Review focuses on anacetrapib as the CETP inhibitor without the mortality signal of torcetrapib (Vasc Health Risk Manag 2012)
- Anacetrapib shrinks medium and small LDL while paradoxically raising the smallest, densest LDL4b subfraction (J Lipid Res 2012)
- A new reverse-phase-array lipoprotein-profiling method shows dalcetrapib, unlike torcetrapib and anacetrapib, spares pre-beta HDL formation (J Lipid Res 2011)
- Eight weeks after stopping anacetrapib, HDL-C remains up to 43.4% higher, tracking residual drug levels and CETP inhibition (Am Heart J 2011)
- Anacetrapib inhibited CETP 94% and boosted macrophage-to-feces cholesterol excretion in hamsters (J Lipid Res 2011)
- Review distinguishes CETP inhibitors from the CETP modulator dalcetrapib by their opposite effects on HDL2-to-HDL3 transfer (Curr Opin Lipidol 2011)
- Population PK/PD modeling picks the 100 mg tablet dose for anacetrapib phase III without a dedicated phase IIb trial to test it (AAPS J 2011)
- DEFINE trial design paper describes screening 2,757 patients and randomizing 1,623 across 153 centers in 20 countries (Am Heart J 2009)
- A high-fat meal can raise anacetrapib exposure up to eight-fold, but age, sex, and obesity barely move it (Br J Clin Pharmacol 2009)
- Anacetrapib leaves simvastatin pharmacokinetics unchanged while adding incremental LDL-C lowering when combined (Br J Clin Pharmacol 2009)
- Phase 2 dose-ranging trial finds anacetrapib plus atorvastatin cuts LDL-C by 70% and more than doubles HDL-C (Am Heart J 2009)
- Viewpoint charts efforts to optimize anacetrapib into a best-in-class CETP inhibitor (J Med Chem 2021)
- Anacetrapib pharmacokinetics in healthy Chinese subjects closely match those seen in black and white populations (Adv Ther 2021)
- Anacetrapib accumulates to 0.6 mmol/L in mouse adipose tissue without impairing adipose function, even after weight loss (Pharmacol Res Perspect 2019)
- Review asks whether anacetrapib, the fourth CETP inhibitor tested, finally outperforms its predecessor drugs (Cardiol Rev 2019)
- The lipid-lowering effect of anacetrapib is smaller in Black subjects than White subjects despite identical pharmacokinetics (J Clin Pharmacol 2018)
- Anacetrapib reproduced the CETP-deficiency phenotype and showed a highly significant, if moderate, coronary benefit in REVEAL, a review on HDL and atherogenic inflammation notes (Atherosclerosis 2018)
- Update on novel lipid drugs: anacetrapib cut coronary events by 7% but not wider CVD outcomes, leaving CETP inhibitors without further development (Curr Opin Cardiol 2018)
- For lipid management in diabetes, CETP inhibitor trials have generally underwhelmed and are no longer being developed, a review concludes (Diabet Med 2018)
- CETP inhibitors as agents to reduce coronary heart disease risk: after earlier trial failures, REVEAL showed anacetrapib actually works (Cardiol Clin 2018)
- Nat Rev Cardiol commentary: the REVEAL coronary benefit from CETP inhibition is probably down to lowering non-HDL-C, not raising HDL-C (Nat Rev Cardiol 2017)
- A single dose of anacetrapib inhibits CETP equally well in young Japanese and white men, with a Japanese breakfast boosting exposure similarly (J Clin Pharmacol 2018)
- Review weighs whether anacetrapib can succeed as a cardioprotective CETP inhibitor where earlier drugs failed (Drug Des Devel Ther 2017)
- Review asks whether anacetrapib is the last surviving CETP inhibitor as REVEAL results loom (Expert Opin Pharmacother 2016)
- The LDL-C and HDL-C effects of anacetrapib were smaller in Black than White DEFINE trial patients (J Clin Lipidol 2015)
- Neither moderate hepatic nor severe renal impairment meaningfully alters anacetrapib pharmacokinetics (J Clin Pharmacol 2014)
- Unlike torcetrapib, anacetrapib raises HDL-C by 138% without elevating blood pressure or disturbing electrolytes (Cardiol Rev 2014)
- Chronic rifampin dosing slashes anacetrapib exposure by 65% through CYP3A induction, while a single dose barely moves it (J Clin Pharmacol 2013)
- Anacetrapib has no clinically meaningful interaction with warfarin, sparing patients a dosage adjustment (Br J Clin Pharmacol 2012)
- Review positions anacetrapib as free of the off-target toxicity of torcetrapib, with phase III trial results still awaited (Expert Opin Investig Drugs 2012)
- Anacetrapib does not meaningfully inhibit P-glycoprotein, leaving digoxin exposure essentially unchanged (Biopharm Drug Dispos 2011)
- Review by the developers of anacetrapib frames CETP inhibition as a new approach to cutting cardiovascular risk (Clin Pharmacol Ther 2012)
- Review calls anacetrapib a new weapon against dyslipidemia, pending long-term mortality data (Curr Clin Pharmacol 2011)
- Review finds anacetrapib and dalcetrapib safely raise HDL-C without the off-target effects that doomed torcetrapib (Ann Pharmacother 2011)
- Review asks whether anacetrapib offers the greatest HDL-raising, LDL-lowering promise among CETP inhibitors (Cardiovasc Ther 2011)
- Drug profile tracks the path of anacetrapib from Merck development into a 76-week international phase III trial (Am J Cardiovasc Drugs 2010)
- Anacetrapib shows moderate oral bioavailability in rats and monkeys, with most of the dose excreted unchanged in feces (Drug Metab Dispos 2010)
- Nearly 87% of an oral anacetrapib dose is eliminated unchanged in feces, with only trace CYP3A4-generated metabolites (Drug Metab Dispos 2010)
- Review finds the lipoprotein effects of anacetrapib surpass both torcetrapib and dalcetrapib, though long-term safety remains unproven (Curr Opin Investig Drugs 2009)
- Anacetrapib neither inhibits nor induces CYP3A, but ketoconazole raises its own exposure more than fourfold (J Clin Pharmacol 2009)
- Review asks whether JTT-705 (dalcetrapib) or anacetrapib can still succeed after the collapse of torcetrapib (Expert Opin Investig Drugs 2008)
- A validated mass spectrometry assay quantifies anacetrapib in fat tissue across three animal species and humans (Bioanalysis 2024)
- Review of new oral dyslipidaemia drugs names anacetrapib the only CETP antagonist that reduces cardiovascular events (Eur J Prev Cardiol 2020)
- Shrinking anacetrapib nanoparticles below 100 nm boosts bioavailability in dogs beyond what dissolution rate alone explains (J Pharm Sci 2019)
- Pharmacokinetic review details the long elimination half-life and faeces-dominant clearance of anacetrapib (Expert Opin Drug Metab Toxicol 2017)
- Dalcetrapib, but not anacetrapib, raises plasma and liver levels of the dietary antioxidants lutein and zeaxanthin (Lipids 2014)
- Review collates the bioanalytical methods developed to quantify anacetrapib, dalcetrapib, and torcetrapib in biological samples (Biomed Chromatogr 2013)
- A new palladium-catalysed C-H fluorination reaction offers a concise late-stage route to anacetrapib (Chem Commun 2021)
- LC-MS/MS method measures anacetrapib pharmacokinetics and low protein binding in rats (Biomed Chromatogr 2017)
- LC-MS/MS method quantifies anacetrapib, a stable-isotope tracer, and four metabolites in human plasma (J Chromatogr B 2016)
- Isotope-labeled anacetrapib and its metabolites are synthesized to support bioavailability and drug-metabolism studies (J Labelled Comp Radiopharm 2013)
- A hidden solvent impurity turns out to enable a scalable, chromatography-free synthesis of the anacetrapib biaryl core (J Org Chem 2011)
- AHA 2010 trials update reports DEFINE found no adverse safety signal for anacetrapib (Cardiovasc Drugs Ther 2011)