Kumar Ashish

Cardiovascular Outcomes of PCSK9 Inhibitors: With Special Emphasis on Its Effect beyond LDL-Cholesterol Lowering

PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs. FDA first approved them in July 2015. PCSK9 protein (692-amino acids) was discovered in 2003. It plays a major role in LDL receptor degradation and is a prominent modulator in low-density lipoprotein cholesterol (LDL-C) metabolism. PCSK9 inhibitors are monoclonal antibodies that target PCSK9 protein in liver and inhibiting this protein leads to drastically lowering harmful LDL-C level in the bloodstream. Despite widespread use of the statin, not all the high-risk patients were able to achieve targeted level of LDL-C. Using PCSK9 inhibitors could lead to a substantial decrement in LDL-C plasma level ranging from 50% to 70%, either as a monotherapy or on top of statins. A large number of trials have shown robust reduction of LDL-C plasma level with the use of PCSK9 inhibitors as a monotherapy or in combination with statins in familial and nonfamilial forms of hypercholesterolemia. Moreover, PCSK9 inhibitors do not appear to increase the risk of hepatic and muscle-related side effects. PCSK9 inhibitors proved to be a highly potent and promising antihypercholesterolemic drug by decreasing LDL-R lysosomal degradation by PCSK9 protein. Statin drugs are known to have some pleiotropic effects. In this article, we are also focusing on the effects of PCSK9 inhibitor beyond LDL-C reduction like endothelial inflammation, atherosclerosis, its safety in patients with diabetes, obesity, and chronic kidney disease, and its influence on neurocognition and stroke.

Safety and Efficacy of Extremely Low LDL-Cholesterol Levels and Its Prospects in Hyperlipidemia Management

The risk of cardiovascular disease has been reported to have a linear relationship with LDL levels. Additionally, the currently recommended LDL target goal of 70 mg/dl does not diminish the CV risk entirely leaving behind some residual risk. Previous attempts to maximally lower the LDL levels with statin monotherapy have met dejection due to the increased side effects associated with the treatment. Nevertheless, with the new advancements in clinical medicine, it has now become possible to bring down the LDL levels to as low as 15 mg/dl using PCSK9 monoclonal antibodies alone or in combination with statins. The development of inclisiran, siRNA silencer targeting PCSK9 gene, is a one step forward in these endeavors. Moreover, various studies aiming to lower the CV risk and mortality by lowering LDL levels have demonstrated encouraging results. The current challenge is to explore this arena to redefine the target LDL levels, if required, to avoid any suboptimal treatment. After thorough literature search in the PubMed, Embase, Scopus, and Google Scholar, we present this article to provide a brief overview of the safety and efficacy of lowering LDL below the current goal.

Role of quantitative myocardial-iron in hemodialysis-dependent end-stage renal disease subjects

Article history: Received 20 November 2017 Accepted 21 November 2017 function in hemodialysis-dependent ESRD patients. Their study also demonstrated that regardless of clinical rectification of SF and liver iron level, hemodialysis-dependent ESRDpatients havemyocardial iron inadequacy. Myocardial-iron was found to be an independent and critical indicator of LV dysfunction, as iron deficiency is associated with myocyte