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Maternal dyslipidemia and altered cholesterol metabolism in early pregnancy as a risk factor for small for gestational age neonates.
Kim, SY, Lee, SM, Kwon, GE, Kim, BJ, Koo, JN, Oh, IH, Kim, SM, Shin, S, Kim, W, Joo, SK, et al
Scientific reports. 2021;(1):21066
Abstract
We evaluated the relationship between maternal cholesterol levels and its biologically active precursors and metabolites in the first trimester and subsequent risk for small-for-gestational-age birthweight (SGA). This is a secondary analysis of a prospective cohort study which enrolled healthy singleton pregnancies (n = 1337). Maternal fasting blood was taken in the first trimester and followed up till delivery. The lipid parameters were compared between women who delivered SGA neonates (SGA-group, birthweight < 10th percentile, n = 107) and women who did not (non-SGA-group, n = 1230). In addition, metabolic signatures of cholesterol were evaluated in a subset consisting of propensity-score matched SGA (n = 56) and control group (n = 56). Among lipid parameters, maternal high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in SGA-group than in non-SGA-group (p = 0.022). The risk for SGA was negatively correlated with maternal serum HDL-C quartiles (p = 0.003), and this association remained significant after adjustment for confounding variables. In metabolic signatures of cholesterol, the cholesterol/lathosterol ratio in SGA-group was significantly higher than non-SGA-group [(2.7 (1.6-3.7) vs. 2.1 (1.5-2.9), respectively; p = 0.034)], suggesting increased endogenous cholesterol biosynthesis. We demonstrated that dyslipidemia and increased cholesterol biosynthesis led to delivery of SGA neonates even in early pregnancy.
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Efficacy and Safety of Triple Therapy With Telmisartan, Amlodipine, and Rosuvastatin in Patients With Dyslipidemia and Hypertension: The Jeil Telmisartan, Amlodipine, and Rosuvastatin Randomized Clinical Trial.
Hong, SJ, Jeong, HS, Cho, JM, Chang, K, Pyun, WB, Ahn, Y, Hyon, MS, Kang, WC, Lee, JH, Kim, HS
Clinical therapeutics. 2019;(2):233-248.e9
Abstract
PURPOSE Fixed-dose combination therapy with telmisartan, amlodipine, and rosuvastatin is needed in patients with hypertension and dyslipidemia for better adherence and cost-effectiveness than free-equivalent combination therapies. This study aimed to compare the efficacy and safety of combination therapy with telmisartan, amlodipine, and rosuvastatin versus telmisartan plus amlodipine or telmisartan plus rosuvastatin in patients with hypertension and dyslipidemia. METHODS The Jeil Telmisartan, Amlodipine, and Rosuvastatin Randomized Clinical Trial (J-TAROS-RCT) was an 8-week, multicenter, randomized, double-blind, parallel, Phase III clinical trial conducted at 9 hospitals in Korea. After a run-in period of >4 weeks, patients who fulfilled the criteria of the National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for randomization to receive 1 of 3 treatments for 8 weeks: (1) telmisartan/amlodipine 80 mg/10 mg plus rosuvastatin 20 mg, (2) telmisartan/amlodipine 80 mg/10 mg, or (3) telmisartan 80 mg plus rosuvastatin 20 mg. The primary end point was efficacy evaluation of combination therapy with telmisartan/amlodipine/rosuvastatin by comparing the change in mean sitting systolic blood pressure (msSBP) and mean percentage change in LDL-C from baseline after 8 weeks of treatment. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. FINDINGS Among 148 patients, the changes in msSBP from baseline after 8 weeks of treatment were a mean (SD) of -24.41 (2.38) versus -9.31 (2.36) mm Hg in the telmisartan/amlodipine/rosuvastatin and telmisartan/rosuvastatin groups, respectively. Significantly more participants achieved the target BP at week 8 in the telmisartan/amlodipine/rosuvastatin group (41 patients [87.2%]) than in the telmisartan/rosuvastatin group (24 [50.0%], P < 0.001). The changes in mean (SD) LDL-C at 8 weeks compared with baseline values were -57.59% (11.59%) versus 6.08% (20.98%) in the telmisartan/amlodipine/rosuvastatin and telmisartan/amlodipine groups, respectively. The percentages of patients who achieved the target LDL-C according to their risk factors after 8 weeks of treatment were 97.87% vs 6.12% in the telmisartan/amlodipine/rosuvastatin and the telmisartan/amlodipine groups (P < 0.0001), respectively. No significant differences were found in the incidence of overall AEs and adverse drug reactions, and serious AEs were comparable among 3 groups. IMPLICATIONS Fixed-dose combinations of telmisartan, amlodipine, and rosuvastatin decreased BP and LDL-C in patients with hypertension and dyslipidemia. The safety and tolerability profiles of fixed-dose telmisartan, amlodipine, and rosuvastatin combination therapy were comparable with those of telmisartan plus amlodipine or telmisartan plus rosuvastatin. ClinicalTrials.gov identifier: NCT03088254.
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The effect of apple vinegar consumption on glycemic indices, blood pressure, oxidative stress, and homocysteine in patients with type 2 diabetes and dyslipidemia: A randomized controlled clinical trial.
Gheflati, A, Bashiri, R, Ghadiri-Anari, A, Reza, JZ, Kord, MT, Nadjarzadeh, A
Clinical nutrition ESPEN. 2019;:132-138
Abstract
BACKGROUND Some foods and drinks contain special ingredients, causing impressive effects on human health. The aim of the current study was to assess the health effects of apple vinegar in patients with diabetes and dyslipidemia. METHOD Seventy participants with type 2 diabetes and hyperlipidemia were randomly assigned into an intervention and control group in order to assess the effect of 20 ml apple vinegar per day using an 8-week parallel study. Fasting blood sugar (FBS), homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for b-cell function (HOMA-B), quantitative insulin sensitivity checks index (QUICKI), insulin, malondialdehyde (MDA), 2,20-Diphenyl-1- picrylhydrazyl (DPPH), homocysteine, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured at the beginning and end of the study. RESULTS The intervention with apple vinegar could significantly improve FBS (mean change: -10.16 ± 19.48 mg/dl, p = 0.006) and DPPH (mean change: 16.58 ± 11.56, p < 0.001) within intervention group and in comparison with control group (p < 0.001). Additionally, the significant increase of MDA in control group (p < 0.05) caused a considerable difference between two groups. Glycemic indices containing insulin, HOMA-IR, HOMA-B, and QUICKI decrease significantly in both groups (p < 0.05). No considerable effect was observed on blood pressure and homocysteine in intervention group as well as control group. CONCLUSION This trial provided some evidences that apple vinegar consumption may cause beneficial effects on glycemic indices and oxidative stress in individuals with diabetes and dyslipidemia. This randomized clinical trial was registered in the Iranian Registry of Clinical Trials (https://www.irct.ir/) as 2013070710826N5.
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Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial.
Ishibashi, S, Arai, H, Yokote, K, Araki, E, Suganami, H, Yamashita, S, ,
Journal of clinical lipidology. 2018;(1):173-184
Abstract
BACKGROUND To overcome the concerns associated with the use of fibrates, pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor modulator, was developed. In a previous phase 2 trial, we showed excellent efficacy and safety of pemafibrate in patients with dyslipidemia. OBJECTIVE The objective of the study was to evaluate the efficacy and safety of pemafibrate over 24 weeks in adults with dyslipidemia in comparison with fenofibrate. METHODS In this multicenter, 24-week, double-blind, clinical study, 225 patients with high triglyceride (TG; ≥150 mg/dL [1.7 mmol/L] and <500 mg/dL [5.7 mmol/L]) and relatively low high-density lipoprotein cholesterol (<50 mg/dL [1.3 mmol/L] in men or 55 mg/dL [1.4 mmol/L] in women) levels were randomized to receive either pemafibrate at 0.2 or 0.4 mg/d or fenofibrate 106.6 mg/d. RESULTS Pemafibrate 0.2, 0.4 mg/d and fenofibrate significantly reduced TG levels from baseline by -46.2%, -45.9%, and -39.7%, respectively. As compared with fenofibrate, the least squares mean differences (95% confidence intervals) in TG were -6.5% (-12.0, -1.1) and -6.2% (-11.6, -0.8) in pemafibrate 0.2 and 0.4 mg/d respectively, which showed the superiority of these doses of pemafibrate to 106.6 mg/d of fenofibrate. The incidence rates of adverse drug reactions in pemafibrate groups (2.7% and 6.8%) were significantly lower than that in the fenofibrate group (23.7%). Pemafibrate significantly decreased alanine aminotransferase and gamma-glutamyltransferase levels, whereas fenofibrate increased both of them. The increments of serum creatinine and cystatin C were smaller in pemafibrate than those in fenofibrate. CONCLUSIONS Pemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety.
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Study of Saroglitazar in Treatment Of Pre-diabetes with Dyslipidemia: STOP-D.
Bhosle, D, Bhosle, V, Bobde, J, Bhagat, A, Shaikh, H, Kadam, R
The Journal of the Association of Physicians of India. 2018;(3):14-7
Abstract
OBJECTIVES Patients with prediabetes are not only at increased risk of progression to type 2 diabetes, but they are also at high risk of developing cardiovascular risk compared to normoglycemic people. Further, prediabetes is also often associated with abnormal lipid levels (dyslipidemia). We therefore aimed to evaluate the effect of Saroglitazar in patients with prediabetes and dyslipidemia. METHODS This was a prospective, single centre, single arm study involving patients with pre-diabetes and dyslipidemia. Subjects with baseline HbA1c 5.7-6.4% and dyslipidemia (Total cholesterol > 200mg/dl, LDL-C > 130 mg/dl, triglycerides > 150 mg/dl and HDL< 40 mg/dl) were enrolled in this study. Subjects with on-going medications affecting blood glucose or lipids were excluded from the study. Saroglitazar 4mg once daily was administered for a period of 24 weeks. The primary outcome was change in serum triglycerides and secondary outcome parameters included changes in other lipid parameters and HbA1c levels at 24 weeks follow-up. RESULTS Forty patients with prediabetes and dyslipidemia were enrolled in the study. At 24 weeks follow-up, serum triglycerides was significantly reduced from 348 ± 86.98 mg/dl to 216.4 ± 72.34 mg/dl (P <0.0001). HbA1c was significantly reduced from 6.3 ± 0.16 % to 5.5 ± 0.30 % after 24 weeks of Saroglitazar therapy (P<0.0001). There were significant improvements observed in other lipid parameters at 24 weeks follow-up period. Saroglitazar was found to be safe and well tolerated, no serious adverse event reported during entire study period. CONCLUSION Saroglitazar is safe and effective in prediabetes with dyslipidemia by exerting its dual lipid lowering and glycemic actions.
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Alirocumab vs usual lipid-lowering care as add-on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM-DYSLIPIDEMIA randomized trial.
Ray, KK, Leiter, LA, Müller-Wieland, D, Cariou, B, Colhoun, HM, Henry, RR, Tinahones, FJ, Bujas-Bobanovic, M, Domenger, C, Letierce, A, et al
Diabetes, obesity & metabolism. 2018;(6):1479-1489
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Abstract
AIM: To compare alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM-DYSLIPIDEMIA trial (NCT02642159). MATERIALS AND METHODS The UC options (no additional lipid-lowering therapy; fenofibrate; ezetimibe; omega-3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open-label alirocumab 75 mg every 2 weeks (with increase to 150 mg every 2 weeks at week 12 if week 8 non-HDL cholesterol concentration was ≥2.59 mmol/L [100 mg/dL]) or UC for 24 weeks. The primary efficacy endpoint was percentage change in non-HDL cholesterol from baseline to week 24. RESULTS The randomized population comprised 413 individuals (intention-to-treat population, n = 409; safety population, n = 412). At week 24, the mean non-HDL cholesterol reductions were superior with alirocumab (-32.5% difference vs UC, 97.5% confidence interval -38.1 to -27.0; P < .0001). Overall, 63.6% of alirocumab-treated individuals were maintained on 75 mg every 2 weeks. Alirocumab also reduced LDL cholesterol (-43.0%), apolipoprotein B (-32.3%), total cholesterol (-24.6%) and LDL particle number (-37.8%) at week 24 vs UC (all P < .0001). Consistent with the overall trial comparison, alirocumab reduced non-HDL cholesterol to a greater degree within each UC stratum at week 24. The incidence of treatment-emergent adverse events was 68.4% (alirocumab) and 66.4% (UC). No clinically meaningful effect on glycated haemoglobin, or change in number of glucose-lowering agents, was seen. CONCLUSIONS In individuals with T2DM and mixed dyslipidaemia on maximally tolerated statin, alirocumab showed superiority to UC in non-HDL cholesterol reduction and was generally well tolerated.
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Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter, Randomized, 4-arm, Double-blind, Placebo-controlled, Phase III Study.
Oh, GC, Han, JK, Han, KH, Hyon, MS, Doh, JH, Kim, MH, Jeong, JO, Bae, JH, Kim, SH, Yoo, BS, et al
Clinical therapeutics. 2018;(5):676-691.e1
Abstract
PURPOSE Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations. METHODS This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared. FINDINGS A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups. IMPLICATIONS Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.
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Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised, double-blind, superiority trial.
Aberg, JA, Sponseller, CA, Ward, DJ, Kryzhanovski, VA, Campbell, SE, Thompson, MA
The lancet. HIV. 2017;(7):e284-e294
Abstract
BACKGROUND People living with HIV-1 infection are at greater risk for cardiovascular disease than seronegative adults. Treatment of dyslipidaemia with statins has been challenging in people with HIV because of an increased potential for drug interactions due to competing cytochrome P450 metabolism between statins and commonly used antiretroviral agents. Neither pitavastatin nor pravastatin depend on cytochrome P450 for primary metabolism. We aimed to assess the safety and efficacy of pitavastatin versus pravastatin in adults with HIV and dyslipidaemia. METHODS In the INTREPID (HIV-infected patieNts and TREatment with PItavastatin vs pravastatin for Dyslipidemia) randomised, double-blind, active-controlled, phase 4 trial (INTREPID, we recruited adults aged 18-70 years with controlled HIV (with CD4 counts >200 cells per μL and HIV-1 RNA <200 copies per mL) on antiretroviral therapy for at least 6 months and dyslipidaemia (LDL cholesterol 3·4-5·7 mmol/L and triglycerides ≤4·5 mmol/L) from 45 sites in the USA and Puerto Rico. Patients being treated with darunavir, or who had homozygous familial hypercholesterolaemia or any condition causing secondary dyslipidaemia, or a history of statin intolerance, diabetes, or coronary artery disease were not eligible. We randomly assigned patients (1:1) to pitavastatin 4 mg or pravastatin 40 mg with matching placebos once daily orally for 12 weeks, followed by a 40 week safety extension. Randomisation was stratified by viral hepatitis B or C coinfection and computer-generated. Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. The primary endpoint was percentage change in fasting serum LDL cholesterol from baseline to week 12 and the primary efficacy analysis was done in the modified intention-to-treat population. The safety analysis included all patients who took at least one dose of study medication. This study is registered with ClinicalTrials.gov, number NCT01301066. FINDINGS Between Feb 23, 2011, and March 29, 2013, we randomly assigned 252 patients to the pitavastatin (n=126) or pravastatin group (n=126). LDL cholesterol reduction was 31·1% with pitavastatin and 20·9% with pravastatin (least squares mean difference -9·8%, 95% CI -13·8 to -5·9; p<0·0001) at 12 weeks. At week 52, four patients (3%) in the pitavastatin group and six (5%) in the pravastatin group had virological failure, with no significant difference between treatments. Both treatments had neutral effects on glucose metabolism parameters. 85 patients treated with pitavastatin (68%) and 88 patients treated with pravastatin (70%) reported treatment-emergent adverse events, and these caused study discontinuation in six patients (5%) versus five patients (4%). No serious adverse event occurred in more than one participant and none were treatment-related according to investigator assessment. The most common treatment-emergent adverse events were diarrhoea in the pitavastatin group (n=12, 10%) and upper respiratory tract infection in the pravastatin group (n=14, 11%). 11 treatment-emergent serious adverse events were noted in seven patients (6%) in the pitavastatin group (atrial septal defect, chronic obstructive pulmonary disease, chest pain, diverticulitis, enterovesical fistula, gastroenteritis, viral gastroenteritis, herpes dermatitis, multiple fractures, respiratory failure, and transient ischaemic attack) and four events in three patients (2%) in the pravastatin group (cerebrovascular accident, arteriosclerosis coronary artery, myocardial infraction, and muscle haemorrhage). In the pravastatin treatment group, one additional patient discontinued due to an adverse event (prostate cancer that was diagnosed during the screening period, 42 days before first dose of study treatment, and therefore was not a treatment-emergent adverse event). INTERPRETATION The INTREPID results support guideline recommendations for pitavastatin as a preferred drug in the treatment of dyslipidaemia in people with HIV. FUNDING Kowa Pharmaceuticals America and Eli Lilly and Company.
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Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients: A randomized, double blind, active- and placebo-controlled, phase 2 trial.
Ishibashi, S, Yamashita, S, Arai, H, Araki, E, Yokote, K, Suganami, H, Fruchart, JC, Kodama, T, ,
Atherosclerosis. 2016;:36-43
Abstract
BACKGROUND AND AIMS To assess the efficacy and safety of K-877 (Pemafibrate), a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) that possesses unique PPARα activity and selectivity, compared with placebo and fenofibrate in dyslipidaemic patients with high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. METHODS AND RESULTS This study was a double blind, placebo-controlled, parallel-group 12-week clinical trial. The study randomized 224 patients to K-877 0.025, 0.05, 0.1, 0.2 mg BID, fenofibrate 100 mg QD, or placebo (1:1:1:1:1:1) groups. Least squares mean percent changes from the baseline TG levels were -30.9%, -36.4%, -42.6%, -42.7% for the K-877 0.025, 0.05, 0.1, 0.2 mg BID respectively (p < 0.001), which were greater than that of the fenofibrate 100 mg QD (-29.7%, p < 0.001) group. Statistically significant improvements from the baseline HDL-C, very-low-density lipoprotein cholesterol, chylomicron cholesterol, remnant lipoprotein cholesterol, apolipoprotein (apo) B (apoB), and apoC-III were also observed in the K-877 groups. The incidence of adverse events (AEs) in the K-877 groups (32.4-56.8%) was comparable to those in placebo (47.2%) and fenofibrate 100 mg QD (56.8%); adverse drug reactions (ADRs) in the K-877 groups (2.7-5.4%) were less than those in placebo (8.3%) and fenofibrate 100 mg QD (10.8%) groups. CONCLUSION In dyslipidaemic patients with high TG and low HDL-C, K-877 improved TG, HDL-C, and other lipid parameters without increasing AEs or ADRs, compared to placebo and fenofibrate. K-877 can be expected to improve atherogenicity and to be a new beneficial treatment for dyslipidaemic patients.
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Effects of the cholesteryl ester transfer protein inhibitor, TA-8995, on cholesterol efflux capacity and high-density lipoprotein particle subclasses.
van Capelleveen, JC, Kastelein, JJ, Zwinderman, AH, van Deventer, SJ, Collins, HL, Adelman, SJ, Round, P, Ford, J, Rader, DJ, Hovingh, GK
Journal of clinical lipidology. 2016;(5):1137-1144.e3
Abstract
BACKGROUND TA-8995 is a potent inhibitor of cholesteryl ester transfer protein (CETP) with beneficial effects on lipids and lipoproteins. The effect of TA-8995 on cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and HDL subparticle distribution is largely unknown. OBJECTIVE To assess the effect of the CETP inhibitor TA-8995 on ABCA1- and non-ABCA1-driven CEC and on HDL particle distribution. METHODS Total, non-ABCA1-, and ABCA1-specific CEC from J774 cells and HDL subclass distribution assessed by two-dimensional gel electrophoresis were measured at baseline and after 12-week treatment in 187 mild-dyslipidemic patients randomized to placebo, 1 mg, 5 mg, 10 mg TA-8995, or 10 mg TA-8995 combined with 10 mg rosuvastatin (NCT01970215). RESULTS Compared with placebo, total, non-ABCA1-, and ABCA1-specific CEC were increased dose dependently by up to 38%, 72%, and 28%, respectively, in patients randomized to 10 mg of TA-8995. PreBeta-1 HDL, the primary acceptor for ABCA1-driven cholesterol efflux, was increased by 36%. This increase in preBeta-1 HDL correlated significantly with the total and the ABCA1-driven CEC increase, whereas the high-density lipoprotein cholesterol (HDL-C) increase did not. CONCLUSION TA-8995 dose dependently increased not only total and non-ABCA1-specific CEC but also ABCA1-specific CEC and preBeta-1 HDL particle levels. These findings suggest that TA-8995 not only increases HDL-C levels but also promotes functional properties of HDL particles. This CETP inhibitor-driven preBeta-1 HDL increase is an important predictor of both ABCA1 and total CEC increase, independent of HDL-C increase. Whether these changes in HDL particle composition and functionality have a beneficial effect on cardiovascular outcome requires formal testing in a cardiovascular outcome trial.