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Inclisiran, a small interfering RNA therapeutic, reduces hepatic synthesis of PCSK9. In two separate randomized trials, subcutaneous injections of inclisiran on day 1, day 90, and then every 6 months reduced LDL cholesterol levels by approximately 50% at month 17, with a modest excess of injection-site adverse events.

Phytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However, deeper insights into its mechanism remain unclear. In this randomized controlled study, we assigned 210 mildly hypercholesterolemic subjects from three study centers across China (Beijing, Nanjing, and Shanghai) to consume 80 g of oats or rice daily for 45 days. Plasma lipid profiles, short chain fatty acids (SCFAs), and fecal microbiota were measured. The results showed that total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) decreased significantly with both oats and rice intake after 30 and 45 days. The reduction in TC and non-HDL-C was greater in the participants consuming oats compared with rice at day 45 ( p  = 0.011 and 0.049, respectively). Oat consumption significantly increased the abundance of Akkermansia muciniphila and Roseburia , and the relative abundance of Dialister , Butyrivibrio , and Paraprevotella , and decreased unclassified f-Sutterellaceae. In the oat group, Bifidobacterium abundance was negatively correlated with LDL-C ( p  = 0.01, r  = −0.31) and, TC and LDL-C were negatively correlated to Faecalibacterium prausnitzii ( p  = 0.02, r  = −0.29; p  = 0.03, r  = −0.27, respectively). Enterobacteriaceae , Roseburia , and Faecalibacterium prausnitzii were positively correlated with plasma butyric acid and valeric acid concentrations and negatively correlated to isobutyric acid. HDL-C was negatively correlated with valeric acid ( p  = 0.02, r  = −0.25) and total triglyceride (TG) was positively correlated to isovaleric acid ( p  = 0.03, r  = 0.23). Taken together, oats consumption significantly reduced TC and LDL-C, and also mediated a prebiotic effect on gut microbiome. Akkermansia muciniphila , Roseburia , Bifidobacterium , and Faecalibacterium prausnitzii , and plasma SCFA correlated with oat-induced changes in plasma lipids, suggesting prebiotic activity of oats to modulate gut microbiome could contribute towards its cholesterol-lowering effect.

Participants in an underserved minority population in the United States were randomly assigned to receive a polypill that included low doses of atorvastatin, amlodipine, losartan, and hydrochlorothiazide or to receive usual care. At 12 months, systolic blood pressure and LDL cholesterol levels were significantly lower in the polypill group.

Background This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Methods Data from up to 12 weeks were analyzed to assess the effects of tafolecimab 450 mg every four weeks (Q4W) in patients with T2D and hypercholesterolemia. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Secondary endpoints included the proportion of participants achieving LDL-C levels below 1.8 mmol/L at weeks 12, the proportion of patients achieving LDL-C ≥ 50% reduction and LDL-C < 1.4 mmol/L, as well as percentage changes from baseline to week 12 in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and triglyceride (TG) levels. Results The reduction in LDL-C from baseline was significantly greater in patients receiving tafolecimab than in those receiving placebo (estimated treatment difference: − 64.02%, 95% confidence interval: [− 68.08%, − 59.96%], P  < 0.0001). The proportion of patients achieving a reduction of over 50% and an absolute LDL-C value below 1.4 mmol/L was significantly higher in the tafolecimab group than that in the placebo group ( P  < 0.0001). Furthermore, a significantly greater proportion of patients in the tafolecimab group achieved LDL-C levels below 1.8 mmol/L at week 12 compared to the placebo group ( P  < 0.0001). The tafolecimab group also showed significant reductions in TG, non-HDL-C, apo B, and Lp(a) from baseline to week 12 compared to the placebo group (all P  < 0.001). The incidence of adverse events was generally similar between the two groups. Conclusion Tafolecimab 450 mg Q4W demonstrated a superior lipid-lowering efficacy and favorable safety profile compared to placebo. This suggests it could be a promising new treatment option for Chinese patients with T2D and hypercholesterolemia. Graphical abstract

The ODYSSEY COMBO I study (http://clinicaltrials.gov/show/NCT01644175) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia. This multicenter, phase 3, randomized (2:1 alirocumab vs placebo), double-blind, 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia. Alirocumab (75 mg every 2 weeks [Q2W]) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen. The alirocumab dose was increased to 150 mg Q2W (also 1 mL) at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥70 mg/dL. The primary efficacy end point was percent change in LDL-C from baseline to week 24 (intention-to-treat analysis). At week 24, estimated mean (95% CI) changes in LDL-C from baseline were −48.2% (−52.0% to −44.4%) and −2.3% (−7.6% to 3.1%) for alirocumab and placebo, respectively, an estimated mean (95% CI) difference of −45.9% (−52.5% to −39.3%) (P < .0001). Low-density lipoprotein cholesterol <70 mg/dL was achieved by 75% alirocumab versus 9% placebo patients at week 24. At week 12, 83.2% of evaluable alirocumab-treated patients remained on 75-mg Q2W. Treatment-emergent adverse events were comparable between groups. Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals, versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy. The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups.

Obesity and overweight conditions, frequently accompanied by hypercholesterolemia, are major risk factors for cardiovascular disease. Lifestyle interventions remain the cornerstone of non-pharmacological treatment; however, their effectiveness in improving lipid profiles is limited. Intermittent hypoxic training (IHT) has recently emerged as a potential strategy to enhance metabolic outcomes. This study aimed to evaluate the effects of a 4-week intensive IHT program combined with a calorie-restricted diet on lipid profile and body composition in men with overweight or obesity and secondary hypercholesterolemia. Twenty physically inactive men (35.3 ± 5.4 years) were randomly assigned to either a hypoxic group (H, n = 10) or a normoxic control group (C, n = 10). Both groups followed the same training protocol and diet, differing only in environmental training conditions. Body composition, resting metabolic rate, and blood lipid parameters (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; non-high-density lipoprotein cholesterol, non-HDL-C; Triglycerides, TG) were assessed before and after the intervention. Compared with the C group, participants in the H group achieved significantly greater reductions in body mass (−5.4% vs. −2.6%, p < 0.05) and fat mass (−14.7% vs. −7%, p < 0.01). IHT also induced marked decreases in TC (−22.6%, p < 0.001), LDL-C (−25.8%, p < 0.001), non-HDL-C (−26.5%, p < 0.001), and TG (−31.4%, p < 0.01), along with a significant improvement in the atherogenic index of plasma (AIP, −24.4%, p < 0.05). In contrast, the C group showed only non-significant downward trends. No significant changes in HDL-C were observed in either group. These findings suggest that IHT combined with dietary restriction produces more favorable changes in lipid profile and body composition than normoxic training. IHT may therefore represent a promising adjunct to conventional lifestyle-based interventions in the management of obesity-related hypercholesterolemia.

Among patients who had had an acute coronary syndrome, the risk of death from coronary heart disease, nonfatal myocardial infarction, stroke, or unstable angina requiring hospitalization at 2.8 years was lower among those randomly assigned to alirocumab than among those assigned to placebo.

In this trial, 27,564 patients with cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter or higher on statin therapy were assigned to either evolocumab or placebo. At 2.2 years, the evolocumab group had a significantly lower rate of major adverse cardiovascular events. Low-density lipoprotein (LDL) cholesterol is a well-established and modifiable risk factor for cardiovascular disease. Monoclonal antibodies that inhibit proprotein convertase subtilisin–kexin type 9 (PCSK9) have emerged as a new class of drugs that effectively lower LDL cholesterol levels. 1 Evolocumab, a member of this class, is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60%. 2 – 6 Genetic studies have shown that carriage of PCSK9 loss-of-function alleles is associated with lower LDL cholesterol levels and a reduced risk of myocardial infarction. 7 , 8 Moreover, exploratory data from longer-term follow-up in phase 2 and phase 3 trials of PCSK9 inhibitors . . .

LDL cholesterol is a well established risk factor for atherosclerotic cardiovascular disease. How much one should or safely can lower this risk factor remains debated. We aimed to explore the relationship between progressively lower LDL-cholesterol concentrations achieved at 4 weeks and clinical efficacy and safety in the FOURIER trial of evolocumab, a monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9). In this prespecified secondary analysis of 25 982 patients from the randomised FOURIER trial, the relationship between achieved LDL-cholesterol concentration at 4 weeks and subsequent cardiovascular outcomes (primary endpoint was the composite of cardiovascular death, myocardial infarction, stroke, coronary revascularisation, or unstable angina; key secondary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke) and ten prespecified safety events of interest was examined over a median of 2·2 years of follow-up. We used multivariable modelling to adjust for baseline factors associated with achieved LDL cholesterol. This trial is registered with ClinicalTrials.gov, number NCT01764633. Between Feb 8, 2013, and June 5, 2015, 27 564 patients were randomly assigned a treatment in the FOURIER study. 1025 (4%) patients did not have an LDL cholesterol measured at 4 weeks and 557 (2%) had already had a primary endpoint event or one of the ten prespecified safety events before the week-4 visit. From the remaining 25 982 patients (94% of those randomly assigned) 13 013 were assigned evolocumab and 12 969 were assigned placebo. 2669 (10%) of 25 982 patients achieved LDL-cholesterol concentrations of less than 0·5 mmol/L, 8003 (31%) patients achieved concentrations between 0·5 and less than 1·3 mmol/L, 3444 (13%) patients achieved concentrations between 1·3 and less than 1·8 mmol/L, 7471 (29%) patients achieved concentrations between 1·8 to less than 2·6 mmol/L, and 4395 (17%) patients achieved concentrations of 2·6 mmol/L or higher. There was a highly significant monotonic relationship between low LDL-cholesterol concentrations and lower risk of the primary and secondary efficacy composite endpoints extending to the bottom first percentile (LDL-cholesterol concentrations of less than 0·2 mmol/L; p=0·0012 for the primary endpoint, p=0·0001 for the secondary endpoint). Conversely, no significant association was observed between achieved LDL cholesterol and safety outcomes, either for all serious adverse events or any of the other nine prespecified safety events. There was a monotonic relationship between achieved LDL cholesterol and major cardiovascular outcomes down to LDL-cholesterol concentrations of less than 0·2 mmol/L. Conversely, there were no safety concerns with very low LDL-cholesterol concentrations over a median of 2·2 years. These data support further LDL-cholesterol lowering in patients with cardiovascular disease to well below current recommendations. Amgen.