Patients with ULMCA disease treated with PCI had favorable early outcomes in comparison with the CABG group. At 1 year, LVEF had improved significantly only in the PCI group. After more than 2 years, MACCE-free survival was similar in both groups with a trend toward improved survival after PCI.
Background:
Genetic loss-of-function variants in
ANGPTL3
are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis.
Methods:
Adults with non-high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks). The primary end point was placebo-adjusted percentage change from baseline in non-HDL-C at 24 weeks. Secondary end points included placebo-adjusted percentage changes from baseline in triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and ANGPTL3.
Results:
Two hundred eighty-six subjects were randomized: 44 to placebo and 242 to vupanorsen. The median age was 64 (interquartile range, 58-69) years, 44% were female, the median non-HDL-C was 132.4 (interquartile range, 118.0-154.1) mg/dL, and the median triglycerides were 216.2 (interquartile range, 181.4-270.4) mg/dL. Vupanorsen resulted in significant decreases from baseline over placebo in non-HDL-C ranging from 22.0% in the 60 mg every 2 weeks arm to 27.7% in the 80 mg every 2 weeks arm (all
P
<0.001 for all doses). There were dose-dependent reductions in triglycerides that ranged from 41.3% to 56.8% (all
P
<0.001). The effects on LDL-C and ApoB were more modest (7.9%-16.0% and 6.0%-15.1%, respectively) and without a clear dose-response relationship‚ and only the higher reductions achieved statistical significance. ANGPTL3 levels were decreased in a dose-dependent manner by 69.9% to 95.2% (all
P
<0.001). There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen. Injection site reactions and >3x elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively), and there was a dose-dependent increase in hepatic fat fraction (up to 76%).
Conclusions:
Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non-HDL-C and additional lipid parameters. Injection site reactions and liver enzyme elevations were more frequent at higher doses, and there was a dose-dependent increase in hepatic f at fraction.
OBJECTIVE: To study whether weight reducing treatment modulates serum concentration of TNF-a a and two soluble TNF-a a receptors in obese subjects. SUBJECTS AND MEASUREMENTS: Serum concentrations of TNF-a a and two soluble receptors (sTNF-R1, sTNF-R2), plasma glucose, insulin, total cholesterol, HDL-cholesterol and triglicerides were measured in 27 obese subjects (age 48 AE 12 y, body mass index (BMI): 36 AE 6 kgam 2 ) before and after 3 months weight reducing treatment consisted of a diet & 1000 kcaladay and physical exercises. RESULTS: The mean loss of weight during 3 months' treatment was 9.3 AE 3.3 kg. The serum concentration of TNF-a a decreased after weight loss and at the same time both of the receptors (sTNF-R1,sTNF-R2) increased signi®cantly. CONCLUSION: The observed decrease of the serum concentration of TNF-a a and the increase in both TNF soluble receptors after weight reducing treatment in obese subjects, may be a counter-regulation preventing further weight loss.
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