Tafolecimab in Chinese patients with non-familial hypercholesterolemia (CREDIT-1): a 48-week randomized, double-blind, placebo-controlled phase 3 trial.

Background: Tafolecimab, a fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody developed for the treatment of hypercholesterolemia, demonstrated robust lipid-lowering efficacy and favorable safety in previous short-term studies. We aimed to assess the long-term efficacy and safety of tafolecimab in Chinese non-familial hypercholesterolemia (non-FH) patients. Methods: Non-FH patients at high or very-high cardiovascular risk with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L or non-FH patients with screening LDL-C level ≥3.4 mmol/L and on stable lipid-lowering therapy for at least 4 weeks, were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 450 mg Q4W, tafolecimab 600 mg Q6W, placebo 450 mg Q4W, or placebo 600 mg Q6W, respectively, in the 48-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Findings: A total of 618 patients were randomized and 614 patients received at least one dose of tafolecimab (n = 411) or placebo (n = 203). At week 48, tafolecimab induced significant reductions in LDL-C levels (treatment differences versus placebo [on-treatment estimand]: -65.0% [97.5% CI: -70.2%, -59.9%] for 450 mg Q4W; -57.3% [97.5% CI: -64.0%, -50.7%] for 600 mg Q6W; both P < 0.0001). Significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C < 1.8 mmol/L, and LDL-C < 1.4 mmol/L than placebo group at both dose regimens (all P < 0.0001). Furthermore, tafolecimab significantly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. The most commonly-reported treatment emergent adverse events in the tafolecimab groups included upper respiratory infection, urinary tract infection and hyperuricemia. Interpretation: Tafolecimab dosed at 450 mg Q4W and 600 mg Q6W was safe and showed superior lipid-lowering efficacy versus placebo, providing a novel treatment option for Chinese hypercholesterolemia patients. Funding: This study was sponsored by Innovent Biologics, Inc.

Tafolecimab in Chinese Patients With Hypercholesterolemia (CREDIT-4): A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial.

Background: Tafolecimab is a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, developed for the treatment of hypercholesterolemia. Objectives: The purpose of this study was to assess the efficacy and safety of tafolecimab in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. Methods: Patients with diagnoses of heterozygous familial hypercholesterolemia (HeFH) by the Simon Broome criteria or at high or very high cardiovascular risk with nonfamilial hypercholesterolemia, with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L, were randomized 2:1 to receive tafolecimab or placebo 450 mg every 4 weeks (Q4W) in the 12-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Results: A total of 303 patients were enrolled and received at least 1 dose of tafolecimab (n = 205) or placebo (n = 98). The least squares mean percent change in LDL-C level from baseline to week 12 was -68.9% (SE 1.4%) in the tafolecimab group and -5.8% (1.8%) in the placebo group (difference: -63.0%; [95% CI: -66.5% to -59.6%]; P < 0.0001). More patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C <1.8 mmol/L, and LDL-C <1.4 mmol/L at week 12 than did those in the placebo group (all P < 0.0001). Furthermore, tafolecimab markedly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. During the double-blind treatment period, the most commonly reported adverse events included urinary tract infection (5.9% with tafolecimab vs 4.1% with placebo) and hyperuricemia (3.4% vs 4.1%). Conclusions: Tafolecimab was safe and showed robust lipid-lowering efficacy in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. (A Study of IBI306 in Participants With Hypercholesterolemia; NCT04709536).

The effects of VEGF on deep venous thrombosis in the perioperative period of elderly fracture patients.

Deep venous thrombosis is a very common complication of orthopedic patients on bed rest. In the present study, comparison of the correlation between serum vascular endothelial growth factor (VEGF) with D-Dimer, fibrinogen and thrombo elastogram was done. 68 elderly fractured patients that had undergone surgery were divided into two groups according to whether they were diagnosed with deep venous thrombosis in the perioperative period or not. ELISA assays was carried out to detect the VEGF, D-Dimer and fibrinogen levels prior to operation and post-operation on 1st, 5th & 10th day. SPSS20.0 (IBM US) statistical software was used in the research for statistical data analysis. The measured data was evaluated by using mean ± standard deviation. The present study has found that VEGF levels in both these two groups showed an increase at first followed by a decrease, which indicated that the angiogenesis process after operative injury can cause an increase of serum VEGF levels. The thrombosis group showed higher VEGF levels compared to the non-thrombosis group after the operation for different days; difference was statistically significant (P<0.05). In addition, VEGF levels in the thrombosis group after the operation were closely related to the D-Dimer and fibrinogen content. However, for non-thrombosis group, the relationship between VEGF levels and the content of D-Dimer and fibrinogen was weak.

Troxerutin protects against diabetic cardiomyopathy through NF­κB/AKT/IRS1 in a rat model of type 2 diabetes.

Troxerutin is a bioflavonoid, which can be used to treat venous disorders, thrombosis and cerebrovascular diseases. Recent studies have demonstrated that it may also be used to prevent edemas. However, it is not known whether troxerutin protects against the cardiomyopathic complications of diabetes. In the present study, a rat model of type 2 diabetes was used to investigate the potential for troxerutin to protect against diabetic cardiomyopathy, through changes to nuclear factor­κB (NF­κB) expression. Troxerutin administration significantly reduced heart rate, blood pressure, blood glucose and plasma triglyceride levels across all measured time points. Furthermore, troxerutin significantly reduced reactive oxygen species levels, NF­κB protein expression, and suppressed the phosphorylated forms of AKT, insulin receptor substrate 1 (IRS1) and c­Jun N­terminal kinase (JNK). These results suggested that troxerutin protects against cardiomyopathy via alterations in NF­κB, AKT and IRS1 signaling, in a rat model of type 2 diabetes.