RESUMO
BACKGROUND: Angiopoietin-like 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases and hepatic uptake of triglyceride-rich lipoprotein remnants. ANGPTL3 loss-of-function carriers have lower levels of triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol and a lower risk of atherosclerotic cardiovascular disease than noncarriers. Zodasiran is an RNA interference (RNAi) therapy targeting expression of ANGPTL3 in the liver. METHODS: We conducted a double-blind, placebo-controlled, dose-ranging phase 2b trial to evaluate the safety and efficacy of zodasiran in adults with mixed hyperlipidemia (fasting triglyceride level of 150 to 499 mg per deciliter and either an LDL cholesterol level of ≥70 mg per deciliter or a non-HDL cholesterol level of ≥100 mg per deciliter). Eligible patients were randomly assigned in a 3:1 ratio to receive subcutaneous injections of zodasiran (50, 100, or 200 mg) or placebo on day 1 and week 12 and were followed through week 36. The primary end point was the percent change in the triglyceride level from baseline to week 24. RESULTS: A total of 204 patients underwent randomization. At week 24, substantial mean dose-dependent decreases from baseline in ANGPTL3 levels were observed with zodasiran (difference in change vs. placebo, -54 percentage points with 50 mg, -70 percentage points with 100 mg, and -74 percentage points with 200 mg), and significant dose-dependent decreases in triglyceride levels were observed (difference in change vs. placebo, -51 percentage points, -57 percentage points, and -63 percentage points, respectively) (P<0.001 for all comparisons). Other differences in change from baseline as compared with placebo included the following: for non-HDL cholesterol level, -29 percentage points with 50 mg, -29 percentage points with 100 mg, and -36 percentage points with 200 mg; for apolipoprotein B level, -19 percentage points, -15 percentage points, and -22 percentage points, respectively; and for LDL cholesterol level, -16 percentage points, -14 percentage points, and -20 percentage points, respectively. We observed a transient elevation in glycated hemoglobin levels in patients with preexisting diabetes who received the highest dose of zodasiran. CONCLUSIONS: In patients with mixed hyperlipidemia, zodasiran was associated with significant decreases in triglyceride levels at 24 weeks. (Funded by Arrowhead Pharmaceuticals; ARCHES-2 ClinicalTrials.gov number, NCT04832971.).
RESUMO
PURPOSE: This study evaluated the effectiveness and coaching labor requirements of a web-based automated telehealth (TH) messaging program compared with standard of care (SOC) in newly diagnosed patients with obstructive sleep apnea (OSA). METHODS: In this non-blinded, multicenter, prospective study, all patients were started on continuous positive airway pressure (CPAP) with heated humidification and a wireless modem. They all received standardized CPAP education and setup. Patients in the TH group (n = 58) received an automated series of text messages and/or e-mails that were triggered by preset conditions. Patients in the SOC group (n = 64) received scheduled calls on days 1, 7, 14, and 30. Additional contacts were allowed for patients in both groups as deemed clinically necessary. Coaching labor was calculated by totaling the number and type of patient contacts and assigning historical time values. RESULTS: One hundred twenty-two patients were included in the final analysis. There were no statistically significant differences between the TH and SOC groups for Medicare adherence (83 vs. 73 %), daily CPAP usage (5.1 ± 1.9 h vs. 4.7 ± 2.1 h), CPAP efficacy (mean residual apnea-hypopnea index (3.0 ± 4.1/h vs. 2.8 ± 3.8/h), or change in Epworth Sleepiness Scale score (-5.8 ± 5.5 vs. -5.1 ± 5.9), although all trends favored the TH group. There was, however, a significant reduction in the number of minutes coaching required per patient in the TH vs. SOC group (23.9 ± 26 vs. 58.3 ± 25, 59 % reduction; p < 0.0001). CONCLUSIONS: Use of a web-based telehealth program for CPAP adherence coaching significantly reduced the coaching labor requirement compared with SOC, while maintaining similar adherence and effectiveness.
