Journal of clinical lipidology最新文献

Background: Obicetrapib is a next-generation, oral, selective cholesteryl ester transfer protein inhibitor known to significantly affect atherogenic lipoproteins, including low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (Non-HDL-C), and lipoprotein(a) [Lp(a)].

Objective: To evaluate the lipid-lowering efficacy of obicetrapib based on available evidence.

Methods: This systematic review was drafted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search was conducted to identify randomized clinical trials assessing the lipid-lowering effects of obicetrapib compared to placebo. Fixed- and random-effects models were used.

Results: Five randomized clinical trials (n = 288 patients) were included in this analysis. Patients treated with obicetrapib exhibited significantly greater reductions in LDL-C (mean difference [MD]: 41.4% [95% CI: 45.7 to -37.1]; I²: 6%), ApoB (MD: 26.5% [95% CI: 31.3 to -21.6]; I²: 45%) and Non-HDL-C (MD: 34.5% [95% CI: 37.0 to -31.6]; I²: 80%) compared to those receiving a placebo. Additionally, HDL-C levels were significantly higher in the obicetrapib group (MD: 157.4% [95% CI: 142.2 to 172.6]; I²: 69%). While triglyceride levels did not differ significantly between the 2 groups, Lp(a) levels were notably reduced with obicetrapib treatment (MD: 39.5% [95% CI: 54.6 to -24.3]; I²: 67%).

Conclusion: Obicetrapib is associated with significant reductions in key atherogenic lipoproteins, including LDL-C, ApoB, Non-HDL-C and Lp(a). Further investigation is needed to assess its impact on cardiovascular risk.

Background: Cholesterol Lowering via bEmpedoic Acid Regimen (CLEAR) outcomes, a randomized, double-blind, placebo-controlled cardiovascular outcomes trial, and the largest prospective database of patients with statin intolerance (SI), demonstrated that bempedoic acid reduces low-density lipoprotein cholesterol and cardiovascular risk in patients at high cardiovascular risk.

Objective: Assess baseline differences in SI symptoms and whether these influenced the clinical course during CLEAR outcomes.

Methods: Symptoms and impact of SI on daily living were recorded prior to randomization. This posthoc analysis grouped patients as reporting statin-associated muscle symptoms only (SAMS), nonmuscle adverse effects only (nonSAMS), or BOTH.

Results: Of the 13,970 patients at baseline, 49% reported SAMS, 18% NonSAMS, and 33% BOTH. Moderate/severe impact on daily living was recorded for 62% SAMS, 48% NonSAMS, and 69% BOTH. Baseline lipid modifying treatment (LMT) was used in 43% SAMS, 36% nonSAMS, and 42% BOTH. Drop-in use of moderate/high-intensity statin at any time during the study was higher in the placebo group in all SI groups and higher in SAMS and BOTH vs. nonSAMS, but was not generally maintained at study end. SAMS and BOTH groups had more muscle symptoms and higher rates of treatment discontinuation vs. NonSAMS but there was no difference between treatments.

Conclusion: Patients who reported SAMS, regardless of randomization to bempedoic acid or placebo, had higher rates of discontinuation, higher rates of skeletal muscle symptoms, and a greater percentage of patients to attempt statin rechallenge. These findings indicate patients with history of SAMS may have background factors impacting their tolerance to LMT and may require more focused clinical management.

Clinicaltrials:

Gov identifier: NCT02993406.

Objective: Beyond glucose-lowering, sodium-glucose co-transporter 2 (SGLT2) inhibitors have cardioprotective effects with unclear mechanisms. We examined changes in an extensive panel of plasma lipids, lipoproteins, and apolipoproteins and whether these changes were independent of weight loss, hemoglobin A1c, and hematocrit in patients treated with empagliflozin versus placebo to better understand the observed cardioprotective effects.

Methods: Post-hoc analyses of two double-blind, placebo-controlled trials, the Empire HF trial including 190 patients with heart failure and reduced ejection fraction and the SIMPLE trial including 90 patients with type 2 diabetes randomized to, respectively, 10 mg and 25 mg empagliflozin daily or placebo for 12 weeks.

Results: In studies combined, empagliflozin reduced age and sex adjusted body weight by 1.40 kg (SEM: 0.10; p < 0.001) and hemoglobin A1c by 2.71 mmol/mol (SEM: 0.24; p < 0.001); and increased hematocrit by 1.9% (SEM: 0.12; p < 0.001) compared to placebo. No mean changes were seen in concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, small dense LDL cholesterol, very low-density lipoprotein cholesterol, triglyceride rich lipoprotein cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, apolipoprotein B, lipoprotein(a), HDL cholesterol, and triglycerides adjusted for body weight, hemoglobin A1c, and hematocrit with empagliflozin compared to placebo.

Conclusion: Empagliflozin treatment reduced body weight and hemoglobin A1c; and increased hematocrit. No changes were seen in concentrations of lipids and lipoproteins with empagliflozin compared to placebo. This suggests that the cardioprotective effects of SGLT2 inhibitors are independent of lipid and lipoprotein concentrations.