Lipid Management in Chronic Kidney Disease: Systematic Review of PCSK9 Targeting

AbstractCardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and CKD is considered a coronary artery disease risk equivalent. So far, statins have been the mainstay of primary and secondary prevention of cardiovascular disease in the general population. However, their benefit on outcomes is limited and controversial in CKD patients and new therapeutic approaches to reduce cardiovascular risk are needed. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) in high-risk populations and cardiovascular events in secondary prevention. We now review the limitations of the current approach to lipid management in CKD and information on CKD patients from clinical trials of anti-PCSK9 monoclonal antibodies alirocumab and evolocumab. In CKD sub-group analysis, ODYSSEY COMBO I and ODYSSEY COMBO II studies demonstrated significant superiority of alirocumab on LDL-cholesterol lowering in comparison to placebo and ezetimibe, respectively, when added to statins, and case reports have shown efficacy in nephrotic syndrome. A detailed analysis of CKD subgroups in general population trials of anti-PCSK9 strategies addressing events is needed, given the limited efficacy of statins in CKD both in terms of lipid lowering and events, the high rate of statin non-compliance in these patients, and the high lipoprotein(a) levels. This information should guide th...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research

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Condition:   Familial Hypercholesterolemia Intervention:   Sponsor:   Imperial College London Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
AbstractIn a rapidly expanding population of patients with chronic kidney disease, including 2 million people requiring renal replacement therapy, cardiovascular mortality is 15 times greater than the general population. In addition to traditional cardiovascular risk factors, more poorly defined risks related to uraemia and it ’s treatments appear to contribute to this exaggerated risk. In this context, the microcirculation may play an important early role in cardiovascular disease associated with chronic kidney disease. Experimentally the uraemic environment and dialysis have been linked to multiple pathways causing...
Source: Microcirculation - Category: Research Authors: Tags: REVIEW Source Type: research
SummaryBackgroundPharmacological treatment options for adolescents with obesity are very limited. Glucagon ‐like‐peptide‐1 (GLP‐1) receptor agonist could be a treatment option for adolescent obesity.ObjectiveTo investigate the effect of exenatide extended release on body mass index (BMI) ‐SDS as primary outcome, and glucose metabolism, cardiometabolic risk factors, liver steatosis, and other BMI metrics as secondary outcomes, and its safety and tolerability in adolescents with obesity.MethodsSix ‐month, randomized, double‐blinded, parallel, placebo‐controlled clinical trial in patients (n = 44, 10‐18&thin...
Source: Pediatric Obesity - Category: Eating Disorders & Weight Management Authors: Tags: ORIGINAL RESEARCH Source Type: research
AbstractBackgroundRisk factors for heart disease include arterial hypertension, high cholesterol, tobacco abuse, and obesity. There is a paucity of data regarding role of ethnicity in bariatric surgery (BS) outcomes. The study ’s aim is to determine if ethnicity plays a significant role in BS outcomes, heart age, and cardiovascular risk.MethodsWe conducted a retrospective review of data collected concurrently from patients who underwent BS from 2010 to 2015. We analyzed demographics, comorbidities, heart age, and cardiovascular risk-score at surgery and 12-month follow-up. Ethnicities categorized were Caucasian and A...
Source: Obesity Surgery - Category: Surgery Source Type: research
AbstractIntroductionEzetimibe/statin combination therapy has been reported to provide additional cardioprotective effects compared to statin monotherapy. The apolipoprotein B/A1 (apoB/A1) ratio is an effective predictor of cardiovascular diseases. The aim of this study was to compare the efficacy and safety of rosuvastatin/ezetimibe combination therapy versus rosuvastatin monotherapy using the apoB/A1 ratio in patients with diabetes and hypercholesterolemia.MethodsIn this randomized, multicenter, open-label, parallel-group study, patients were randomly assigned to receive the combination therapy of rosuvastatin 5  mg/...
Source: Diabetes Therapy - Category: Endocrinology Source Type: research
Conclusions: Atorvastatin improved hepatic tissue lipid metabolism and renal function in adenine-induced CKD rats. PMID: 31828139 [PubMed - in process]
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Conclusion: Anti-PLA2R IHC is a specific marker to distinguish primary MN from secondary MN. 
Nephron Extra 2017;7:1 –9
Source: Nephron Extra - Category: Urology & Nephrology Source Type: research
Authors: Mikolasevic I, Žutelija M, Mavrinac V, Orlic L Abstract Patients with chronic kidney disease (CKD), including those with end-stage renal disease, treated with dialysis, or renal transplant recipients have an increased risk for cardiovascular disease (CVD) morbidity and mortality. Dyslipidemia, often present in this patient population, is an important risk factor for CVD development. Specific quantitative and qualitative changes are seen at different stages of renal impairment and are associated with the degree of glomerular filtration rate declining. Patients with non-dialysis-dependent CKD have low high-...
Source: International Journal of Nephrology and Renovascular Disease - Category: Urology & Nephrology Tags: Int J Nephrol Renovasc Dis Source Type: research
Conclusion: Anti-PLA2R IHC is a specific marker to distinguish primary MN from secondary MN. 
Nephron Extra 2017;7:1 –9
Source: Nephron Extra - Category: Urology & Nephrology Source Type: research
In this study, the effectiveness of lipid-lowering therapy on mortality and cardiovascular outcomes is explored.Summary: Mortality is inversely associated with the cholesterol level. The degree of inflammation and wasting is a stronger predictor of mortality than are cholesterol levels. Treatment with statins reduces the risk of death and cardiovascular outcomes among patients not yet requiring renal replacement therapy, but is not effective once dialysis is initiated, most likely because other processes, such as inflammation, not affected by lipid-lowering therapy, dominate in the causal pathway leading to adverse outcome...
Source: Blood Purification - Category: Hematology Source Type: research
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