Background: In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers.
Methods: We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240.
Results: A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg inclisiran regimen produced the greatest reduction in LDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran.
Conclusions: In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company; ORION-1 ClinicalTrials.gov number, NCT02597127 .).
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1056/NEJMoa1615758 | DOI Listing |
World J Diabetes
January 2025
Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China.
Background: At present, the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent, to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes, the report is as follows.
Aim: To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus (T2DM).
Methods: We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated jejunoileal lateral anastomosis.
World J Gastrointest Oncol
January 2025
Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Background: Colorectal cancer (CRC) is a prevalent malignant neoplasm characterized by subtle early manifestations.
Aim: To investigate the correlation among serum lipid profiles, the triglyceride-glucose (TyG) index, and the atherosclerotic index (AI) in patients with CRC. Furthermore, it explored the clinical diagnostic utility of combining serum lipids with cancer antigens in the context of CRC.
Sisli Etfal Hastan Tip Bul
December 2024
Department of Pharmacognosy and Medicinal Plants, University of Mosul, College of Pharmacy, Mosul, Iraq.
Objectives: Adipsin and leptin are adipokines that link adipose tissue dysfunction and increased fat accumulation to obesity-related metabolic disorders. This study aimed to assess the effects of sitagliptin/metformin versus metformin monotherapy on the levels of adipsin, leptin, and lipid profile in type 2 diabetic patients.
Methods: This comparative case-control study included 120 participants divided into four groups: healthy participants, newly diagnosed type 2 diabetic patients, metformin-treated patients, and sitagliptin/metformin-treated patients.
Orphanet J Rare Dis
January 2025
Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Background: Homozygous familial hypercholesterolaemia (HoFH) increases risk of premature cardiovascular events and cardiac death. In severe cases of HoFH, clinical signs and symptoms cannot be controlled well by non-surgical treatments, liver transplantation (LT) currently represents the viable option.
Method: To assess the clinical efficacy, prognosis, and optimal timing of LT for HoFH, a retrospective analysis was conducted on the preoperative, surgical conditions, and postoperative follow-up of children who received an LT for HoFH at the Beijing Friendship Hospital over the period from December 2014 to August 2022.
JAMA Cardiol
January 2025
Program of Medical and Population Genetics, Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard, Cambridge, Massachusetts.
Importance: Treatment to lower high levels of low-density lipoprotein cholesterol (LDL-C) reduces incident coronary artery disease (CAD) risk but modestly increases the risk for incident type 2 diabetes (T2D). The extent to which genetic factors across the cholesterol spectrum are associated with incident T2D is not well understood.
Objective: To investigate the association of genetic predisposition to increased LDL-C levels with incident T2D risk.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!