Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia

Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia

Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

Clinical efficacy of rosuvastatin in lipid management in Chinese patients in Hong Kong / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Rosuvastatin has been claimed to be more potent than other statins in its ability to lower the low-density lipoprotein (LDL) cholesterol levels. This study aimed to investigate the clinical efficacy of rosuvastatin in LDL cholesterol lowering therapy for new or switched hyperlipidaemic Chinese patients.</p><p><b>METHODS</b>This study was a retrospective one in patients who took rosuvastatin in the outpatient clinics of Prince of Wales Hospital during the period of July 1, 2004 to June 30, 2005. The prescribing pattern, the utilization pattern and the side effect profile were recorded. Attainment of lipid goals for each patient was assessed according to the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III guidelines.</p><p><b>RESULTS</b>A total of 261 Chinese patients (mean age (64.8 +/- 12) years; 55.6% male) were recruited into the study. The mean LDL-cholesterol level was (3.50 +/- 1.29) mmol/L prior to Rosuvastatin and (2.30 +/- 1.73) mmol/L after Rosuvastatin treatment (P < 0.0001). Rosuvastatin raised the LDL-cholesterol goal achievement rate from 28.0% to 74.3% in all patients combined (P < 0.0001) and from 11.0% to 79.0% for statin naive patients (P < 0.0001). Approximately 4% of patients developed side effects including myalgia, elevated liver enzymes, and dizziness.</p><p><b>CONCLUSION</b>Rosuvastatin was effective in improving LDL-cholesterol goal attainment and lowering LDL-cholesterol and triglyceride (TG) levels in either newly started or switched patients.</p>

Relationship between obesity and cardiovascular risk factors in elderly Chinese subjects / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the relative effects of degree and distribution of body fat with several cardiovascular disease (CVD) risk factors in elderly Chinese subjects.</p><p><b>METHODS</b>One hundred and thirty-five elderly Chinese individuals (age range, 60-65 y) without any history of significant renal, hepatic or cardiac disease were recruited. Seated blood pressure, anthropometric and fasting plasma biochemical parameters were measured. Student's t-test was used to compare the differences in biochemical and anthropometric markers between cohorts.</p><p><b>RESULTS</b>Males were heavier (64.6 +/- 8.6, 57.2 +/- 8.2kg, P < 0.001), taller (1.65 +/- 0.06, 1.51 +/- 0.05 m, P < 0.001) and their greater body fat was predominantly deposited centrally (Waist-to- hip ratio, 0.91 +/- 0.06, 0.88 +/- 0.07, P < 0.05). Females were more generally obese with increased body mass index (BMI, 23.8 +/- 4.6, 25.0 +/- 3.5 kg/m2, P < 0.05) and percentage body fat [26.3% (24.5%-28.1%) vs 37.2% (36.0%-38.9%), P < 0.001] than the males. However, despite an 11% higher proportion of body fat in females, no significant differences were identified in blood pressure, lipid profile, indices of insulin resistance or albumin-to-creatinine ratios.</p><p><b>CONCLUSION</b>It is likely that central adiposity contributes disproportionately to these metabolic disorders in males even though they are much leaner than elderly Chinese females.</p>

Management of nephropathy in patients with type 2 diabetes / 中华医学杂志(英文版)

<p><b>PURPOSE</b>To review evidence-based management of nephropathy in patients with type 2 diabetes.</p><p><b>DATA SOURCES</b>A literature search (MEDLINE 1966 to 2000) was performed using the key word "diabetic nephropathy". Relevant book chapters were also reviewed.</p><p><b>STUDY SELECTION</b>Well-controlled, prospective landmark studies and expert review articles on diabetic nephropathy were selected.</p><p><b>DATA EXTRACTION</b>Data and conclusions from the selected articles that provide solid evidence to the optimal management of diabetic nephropathy were extracted and interpreted in light of our clinical research experience with many thousands of Hong Kong Chinese patients.</p><p><b>RESULTS</b>Hypertension, long diabetes duration, poor glycaemic control and central obesity are the most important risk factors. Microalbuminuria is a practical marker to predict overt nephropathy in type 2 diabetic patients. Risk factor modification, renal function monitoring and combined therapies are the current integrated approaches to manage patients with diabetic kidney disease. Optimal glycaemic control is the mainstay of treatment but effective antihypertensive therapy is also key to delaying the progression of diabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have important renoprotective actions independent of their blood pressure lowering actions.</p><p><b>CONCLUSIONS</b>Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. Monitoring renal function and screening for microalbuminuria will allow the identification of patients with nephropathy at a very early stage for intervention. Tight glycaemic control and aggressive antihypertensive treatment as well as the use of renin-angiotensin system inhibitors should substantially delay the progression of nephropathy.</p>