High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany.

BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany. METHODS: Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration. RESULTS: Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%). CONCLUSION: In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy.

[Hazards posed by LEDs? : A comparative study]. / Gefahr durch LED-Licht? : Eine vergleichende Untersuchung.

BACKGROUND: The increasing use of light-emitting diodes (LEDs) for lighting applications and displays is giving rise to public and professional concern that blue LED emissions could damage the retina or via the proven influence on the melatonin levels disrupt the human day-night rhythm. OBJECTIVE: The study aimed to measure the emission of LEDs and other relevant light sources and evaluate the results comparatively with the help of suitable evaluation functions in order to recognize whether LEDs differ considerably from other light sources in their hazard potential. MATERIAL AND METHODS: The spectra of a cold white and a warm white LED, a white tablet LED display, a fluorescent tube and a halogen lamp were measured and evaluated together with a sunlight spectrum relative to each other using the blue light hazard retina weighting function and the circadian action function. RESULT: Since LEDs can be very different, relative LED ratings also vary greatly. The warm white LED is the one with the lowest risk of blue light retinal damage and the lowest potential for inhibition of melatonin formation and in this respect even gentler than halogen lamps. For cold white LEDs, the values for photochemical retinal danger as well as for the expected inhibition of melatonin formation are much greater. The values for the tablet LED display are even higher. CONCLUSION: Not only LEDs but all examined light sources emit in the blue spectral range, so that in principle they represent a retinal hazard. Depending on the employed LED type, this hazard may be greater or less compared to conventional light sources but even cold white LEDs are rated slightly better than sunlight at noon. To support consumers it might be helpful to classify LEDs and other illuminants by their potential hazard to the eye, as they are already labelled with respect to their energy efficiency.

[Dyslipidemias : Diagnostics and management]. / Fettstoffwechselstörungen : Diagnostik und Therapie.

For disorders of lipid metabolism the risk-adapted adjustment of low-density lipoprotein (LDL) cholesterol remains the primary treatment target, as a causal role in minimizing the progression of ACVD has been shown. Because of their efficacy in reducing cardiovascular morbidity and mortality, statins are recommended as first-line pharmacological treatment in dyslipidemias. Additionally, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have been shown to significantly reduce cardiovascular events in high-risk patients. Life style changes can improve the plasma lipid profile, particularly in the setting of hypertriglyceridemia. Evaluation of high-density lipoprotein (HDL) cholesterol and lipoprotein(a) provides further information when assessing the individual cardiovascular risk, but direct evidence that pharmacologically targeting HDL cholesterol or Lp(a) results in a reduction of cardiovascular events has not yet been shown.

[ECS guidelines 2016 - dyslipidaemias]. / ESC-Leitlinien 2016 ­ Dyslipidämien.

Dyslipidaemia is a major cause of atherosclerotic cardiovascular disease and its progression towards clinical complications, such as acute coronary syndromes and stroke. In August 2016 the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) issued new joint guidelines for the management of dyslipidaemias. In these new guidelines, the concept of treating patients to a risk-based low-density lipoprotein (LDL) cholesterol target is reinforced. The task force considers LDL cholesterol as the primary target for dyslipidaemia treatment, whereas high-density lipoprotein (HDL) cholesterol is not recommended as a treatment target (based on the failure of HDL cholesterol elevation treatment strategies to reduce cardiovascular risk in recent studies). In patients with a very high risk for cardiovascular events it is recommended to treat to an LDL cholesterol target of less than 70 mg/dl. Moreover, the new guidelines now additionally recommend a > 50% reduction of LDL cholesterol in patients with very high cardiovascular risk patients and baseline levels between 70 and 135 mg/dl as well as in patients with high cardiovascular risk and baseline LDL cholesterol levels between 100 and 200 mg/dl. Statins are recommended as first-line medicinal treatment and the LDL cholesterol goals given imply the more frequent use of maximum tolerated statin therapy, in particular for patients with very high cardiovascular risk. Treatment with ezetimibe in patients with substantially elevated LDL cholesterol levels despite maximum tolerated statin therapy has now received a stronger recommendation (currently IIa recommendation). The guidelines also now include the potential use of the novel proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and a recent ESC/EAS consensus document provides more detailed information on which patients can be considered for treatment with PCSK9 inhibitors, i. e. in particular patients with familial hypercholesterolemia and patients at very high cardiovascular risk who have markedly elevated LDL cholesterol levels despite maximum tolerated statin and ezetimibe therapy.

[Impact of lipid metabolism parameters on the development and progression of coronary artery disease : An update]. / Einfluss der Lipidstoffwechselparameter auf die Entstehung und Progression der koronaren Herzerkrankung : Ein Update.

Disorders of lipid metabolism play a major role in the development and progression of coronary artery disease. Dyslipidemia therefore plays a central role in therapeutic approaches for prevention and treatment of cardiovascular events associated with coronary artery disease. Epidemiological studies have shown an association between various lipid metabolism parameters, the risk of developing coronary artery disease and progression of a pre-existing disease. In particular, increased levels of low-density lipoprotein cholesterol (LDL-C), reduced levels of HDL cholesterol (HDL-C), as well as high levels of triglycerides and increased lipoprotein(a) [Lp(a)] levels can be taken into account when assessing the risk stratification of patients for primary prevention of coronary artery disease. Lifestyle and dietary changes, intensified statin therapy and possibly the addition of ezetimibe remain the major interventions in both primary and secondary prevention of coronary artery disease, as they improve the prognosis particularly by lowering levels of LDL-C. Recently, genetic studies have contributed to extending our understanding of the relationship between lipid metabolism and coronary artery disease. A causal role for progression of coronary artery disease could be demonstrated for LDL-C, Lpa and triglyceride-rich lipoproteins (TRL), which could not be demonstrated for HDL-C in various studies. Furthermore, the effect of reduction of LDL-C by proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and by the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib on cardiovascular events is currently being investigated in large clinical outcome study programs.