Prior trials with monoclonal antibodies to proprotein convertase subtilizin/kexin type 9 (PCSK9) reported robust low density lipoprotein cholesterol (LDL-C) reductions. However, the ability to detect ...potentially beneficial changes in other lipoproteins such as lipoprotein (a), triglycerides, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein (Apo) A1, and adverse events (AEs) was limited by sample sizes of individual trials. We report a pooled analysis from four phase 2 studies of evolocumab (AMG 145), a monoclonal antibody to PCSK9.
The trials randomized 1359 patients to various doses of subcutaneous evolocumab every 2 weeks (Q2W) or 4 weeks (Q4W), placebo, or ezetimibe for 12 weeks; 1252 patients contributed to efficacy and 1314, to safety analyses. Mean percentage (95% CI) reductions in LDL-C vs. placebo ranged from 40.2% (44.6%, 35.8%) to 59.3% (63.7%, 54.8%) among the evolocumab groups (all P < 0.001). Statistically significant reductions in apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides and lipoprotein (a) Lp(a), and increases in HDL-C were also observed. Adverse events (AEs) and serious AEs with evolocumab were reported in 56.8 and 2.0% of patients, compared with 49.2% and 1.2% with placebo. Adjudicated cardiac and cerebrovascular events were reported in 0.3 and 0% in the placebo and 0.9 and 0.3% in the evolocumab arms, respectively.
In addition to LDL-C reduction, evolocumab, dosed either Q2W or Q4W, demonstrated significant and favourable changes in other atherogenic and anti-atherogenic lipoproteins, and was well tolerated over the 12-week treatment period.
Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). In addition, CKD itself is a coronary artery disease ...equivalent due to its atherogenic potential. Despite the role of CKD in ASCVD and recommendations to control lipid levels aggressively, landmark lipid studies have often excluded patients with advanced CKD. Furthermore, there is a scarcity of data on the use and efficacy of lipid-lowering therapy (LLT) in those with CKD in South Africa (SA).
To determine the prevalence and control of dyslipidaemia in a cohort of SA patients with CKD.
A retrospective, cross-sectional observational study of 250 patients with CKD attending the Charlotte Maxeke Johannesburg Academic Hospital renal clinic from 1 July 2019 to 31 July 2020 was carried out. Lipograms, the use of LLT and achievement of target lipid levels were examined.
The median (interquartile range) age of this cohort was 58 (46 - 69) years; 50.4% were males and 64.4% black African. Dyslipidaemia was prevalent in 83.6% (n=209) of patients. A total of 169 (67.6%) patients were on LLT, and of these only 28 (16.6%) achieved the recommended low-density lipoprotein cholesterol (LDL-C) target. Of those not on LLT, 51 (63%) were eligible for LLT and almost all were classified as either very high risk (64.2%) or high risk (28.4%) for ASCVD. Of those on LLT, all were on statin therapy, of which simvastatin at a mean dose of 20 mg daily was the most commonly prescribed LLT.
This cohort comprised a large proportion of patients classified as high or very high risk for ASCVD. Despite this, the use of LLT was inadequate, and <20% of patients were at target LDL-C levels. These data suggest a greater need for awareness of initiating LLT to achieve recommended target LDL-C levels in patients with CKD.
Insulinomas are rare functional neuroendocrine tumours. These tumours present with symptoms of hypoglycaemia, adrenergic and neuroglycopenic symptoms. Insulinomas are usually small in size, making ...them difficult to locate. Diagnosis is often delayed in these cases resulting in lasting neurological complications, often not reversible after surgical removal of the insulinoma. We report a case of a 33-year-old HIV-positive female with delayed presentation of an insulinoma. She presented with a long history of neurological symptoms with lasting neurological sequelae and poor functional status, during which time the diagnosis of insulinoma was repeatedly missed.
The purpose of this study was assess the effect of evolocumab (AMG 145) on lipoprotein (Lp)(a) from a pooled analysis of 4 phase II trials.
Lp(a), a low-density lipoprotein (LDL) particle linked to ...the plasminogen-like glycoprotein apolipoprotein(a), shows a consistent and independent positive association with cardiovascular disease risk in epidemiological studies. Current therapeutic options to reduce Lp(a) are limited.
A pooled analysis of data from 1,359 patients in 4 phase II trials assessed the effects of evolocumab, a fully human monoclonal antibody to PCSK9, on Lp(a), the relationship between Lp(a) and lowering of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B, and the influence of background statin therapy. Lp(a) was measured using a standardized isoform-independent method.
Evolocumab treatment for 12 weeks resulted in significant (p < 0.001) mean (95% confidence interval) dose-related reductions in Lp(a) compared to control: 29.5% (23.3% to 35.7%) and 24.5% (20.4% to 28.7%) with 140 mg and 420 mg, dosed every 2 and 4 weeks, respectively, with no plateau of effect. Lp(a) reductions were significantly correlated with percentages of reductions in LDL-C (Spearman correlation coefficient, 0.5134; p < 0.001) and apolipoprotein B (Spearman correlation coefficient, 0.5203; p < 0. 001). Mean percentage reductions did not differ based on age or sex but the trend was greater in those patients taking statins.
Inhibition of PCSK9 with evolocumab resulted in significant dose-related reductions in Lp(a). While the mean percentage of reduction was significantly greater in those patients with baseline Lp(a) of ≤125 nmol/l, the absolute reduction was substantially larger in those with levels >125 nmol/l.
Background: Diabetes mellitus (DM) is a common secondary cause of dyslipidaemia, particularly if glycaemic control is poor, which in turn is an important risk factor for atherosclerosis and coronary ...artery disease.
Objectives: (1) To study the prevalence and pattern of dyslipidaemia in patients with type 2 DM. (2) To determine the relationship (if any) between HbA
1C
and the lipid profile in type 2 diabetic patients.
Methods: This was a cross-sectional study done in 200 type 2 diabetic patients attending the Diabetic Clinic at the Helen Joseph Hospital. Patients suffering from other known causes of secondary dyslipidaemia were excluded. Each patient's HbA
1C
and lipid profile results were recorded from their clinic files. The lipid profile included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and calculated low-density lipoprotein cholesterol (LDL-C).
Patients with one or more of the above parameters outside the targets recommended by the 2012 South African Dyslipidaemia Guidelines were considered to have uncontrolled dyslipidaemia.
Results: Of the 200 type 2 DM patients studied, 86 (43%) were male and 114 (57%) female.
Despite all patients being treated with lipid-lowering therapy (simvastatin at a mean daily dose of 20 mg), 187 patients (93.5%) did not achieve all their lipid targets. The most prevalent lipid parameter not at target was an LDL-C of ≥ 1.8 mmol/l in nearly 80% of patients. The most common pattern of dyslipidaemia was a combined dyslipidaemia (any two abnormal lipid parameters) affecting a total of 82 out of the 187 patients (43.8%) not reaching recommended targets. No significant relationship was found between HbA
1C
and any of the lipid parameters.
Conclusion: The vast majority of the type 2 diabetic patients studied had dyslipidaemia not meeting recommended targets, despite the use of lipid-lowering therapy in all patients. There is a need for more intensive lipid-lowering therapy, particularly statin therapy in patients with dyslipidaemia. Measures aimed at combating obesity and other lifestyle-related risk factors are also vital and need to be implemented for effectively controlling dyslipidaemia and reducing the burden of CVD.
Cardiovascular disease (CVD) remains a major cause of death worldwide, with dyslipidaemia playing a significant role in the disease process. It is clinically useful to demarcate hypercholesterolaemia ...from hypertriglyceridaemia, with an increased serum low-density lipoprotein (LDL) cholesterol being the most powerful predictor of CVD morbidity and mortality, and a significant elevation in triglyceride levels increasing the risk of acute pancreatitis. Statins (with or without ezetimibe) and fibrates are the current first-line therapy in the management of dyslipidaemia. Although these medications have shown effectiveness in reducing CVD complications, there are patients who require a greater modification in lipid profile or are intolerant of first-line therapy. Novel agents are on the horizon, which have shown to lead to a significant decrease in serum LDL cholesterol. These include the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (which have shown a reduction in CVD morbidity), mipomersen, cholesterol ester transfer protein (CETP) inhibitors and bempedoic acid. Further studies of the clinical benefit of these medications are ongoing. Drugs such as pemfibrate, angiopoietin-like protein 3 (ANGPTL3) inhibitors, apolipoprotein C3 (apo C3) inhibitors and diacylglycerol acyltransferase-1 (DGAT 1) inhibitors have shown promising results in the management of hypertriglyceridaemia. It is hoped that these exciting new technological advancements in the future management of dyslipidaemia will result in clinical benefit for patients.
Introduction: Atherosclerotic cardiovascular disease is a major contributor to morbidity and mortality in diabetic patients. Strict goal-directed lipid control in patients with diabetes is associated ...with better cardiovascular outcomes.
Aim: The main aim of this study is to describe the lipid profiles of a cohort of patients with type 2 diabetes mellitus in order to highlight the quality of lipid control by correlating the type and dose of lipid-modifying therapy used with lipid levels.
Method: A retrospective analysis was performed on 200 type 2 diabetic patients who attended the Charlotte Maxeke Johannesburg Academic Hospital diabetic clinic. Their lipid profiles and the type and dose of lipid-modifying therapy prescribed was assessed.
Results: Although the majority of participants (146 73%) were at the ideal level for total cholesterol, fewer (133 66.5%) were at the ideal level for triglycerides and 112 (56%) participants were at the ideal level for HDL cholesterol, only 53 (26.5%) participants were at target for LDL cholesterol, and very few, only 25 (12.5%), participants were at target for all four lipid parameters.
Conclusion: Higher doses of statins or the use of more potent statins with or without the addition of other lipid modifying drugs is recommended in order to achieve LDL cholesterol target in the majority of patients with type 2 diabetes.
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