The New England journal of medicine
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Randomized Controlled Trial Multicenter Study
Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia.
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. ⋯ 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.).
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Randomized Controlled Trial Multicenter Study
Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia.
Persons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non-high-density lipoprotein (HDL) cholesterol level, which is driven by remnant cholesterol in triglyceride-rich lipoproteins. The metabolism and clearance of triglyceride-rich lipoproteins are down-regulated through apolipoprotein C3 (APOC3)-mediated inhibition of lipoprotein lipase. ⋯ In this randomized, controlled trial involving participants with mixed hyperlipidemia, plozasiran, as compared with placebo, significantly reduced triglyceride levels at 24 weeks. A clinical outcomes trial is warranted. (Funded by Arrowhead Pharmaceuticals; MUIR ClinicalTrials.gov number NCT04998201.).
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Randomized Controlled Trial Multicenter Study Comparative Study
Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.
Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. ⋯ In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).
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Randomized Controlled Trial Multicenter Study Comparative Study
Doxorubicin-Trabectedin with Trabectedin Maintenance in Leiomyosarcoma.
The addition of trabectedin to doxorubicin, followed by trabectedin maintenance, may have superior efficacy to doxorubicin alone as first-line treatment in patients with advanced leiomyosarcoma. ⋯ Combination therapy with doxorubicin and trabectedin induction, followed by trabectedin maintenance, was associated with improved overall survival and progression-free survival, as compared with doxorubicin alone, among patients with metastatic or surgically unresectable uterine or soft-tissue leiomyosarcoma. (Funded by PharmaMar and others; LMS04 ClinicalTrials.gov number, NCT02997358.).
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Randomized Controlled Trial Multicenter Study
A Monoclonal Antibody to PACAP for Migraine Prevention.
Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) is a new avenue for treating migraine. The efficacy and safety of intravenous Lu AG09222, a humanized monoclonal antibody directed against the PACAP ligand, for migraine prevention are unclear. ⋯ In a phase 2 trial, a single intravenous infusion of 750 mg of Lu AG09222 showed superiority over placebo in reducing migraine frequency over the subsequent 4 weeks. (Funded by H. Lundbeck; HOPE ClinicalTrials.gov number, NCT05133323.).