Search

A recent analysis of a commercially insured US population found fewer cardiovascular disease (CVD) events in high-risk patients attaining low levels of low-density lipoprotein (LDL), as measured by LDL particle number (LDL-P) versus low LDL cholesterol (LDL-C). Here, we investigated the cost effectiveness of LDL-lowering therapy guided by LDL-P. Patients were selected from the HealthCore Integrated Research Database and followed for 12 to 36 months. Patients who achieved LDL-P <1,000 nmol/l were placed into the LDL-P cohort, whereas those without LDL-P tests, but who achieved LDL-C <100 mg/dl, were placed into the LDL-C cohort. CVD-related costs included all health plan paid amounts related to CVD events or lipid management. Cost effectiveness was assessed through incremental cost-effectiveness ratios, defined as difference in total costs across the cohorts divided by difference in CVD events, measured over follow-up. Each cohort included 2,094, 1,242, and 705 patients over 12-, 24-, and 36-month follow-up. Patients in the LDL-P cohort received more aggressive lipid-lowering therapy and had fewer CVD events during follow-up compared to patients in the LDL-C cohort. This led to greater pharmacy costs and lower medical costs over time. Incremental cost-effectiveness ratio estimates ranged from $23,131 per CVD event avoided at 12 months to $3,439 and -$4,555 at 24- and 36-month follow-up, suggesting a high likelihood that achieving LDL-P <1,000 nmol/l is cost effective. In conclusion, LDL-lowering therapy guided by LDL-P was demonstrated to be cost effective, with greater clinical and economic benefit seen over longer time horizons and with the increased use of generic statins., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to examine the efficacy and safety of mipomersen for reducing atherogenic lipids and lipoproteins in patients with hypercholesterolemia., Background: Many patients on lipid-lowering therapies remain unable to achieve target low-density lipoprotein (LDL) cholesterol levels. Mipomersen, an antisense oligonucleotide inhibitor of apolipoprotein B, reduces LDL cholesterol and atherogenic lipoproteins., Methods: This randomized, double-blind, multicenter study enrolled 158 patients with baseline LDL cholesterol levels ≥100 mg/dl with, or at high risk for, coronary heart disease who were receiving maximally tolerated lipid-lowering therapy. Patients received weekly subcutaneous mipomersen 200 mg (n = 105) or placebo (n = 52) for 26 weeks, with a 24-week follow-up period. Randomization was stratified by type 2 diabetes status., Results: Sixty mipomersen and 44 placebo patients completed treatment. Mean baseline LDL cholesterol levels were 122.7 and 122.6 mg/dl in the placebo and mipomersen patients, respectively. Mipomersen reduced LDL cholesterol by -36.9% compared with placebo at -4.5% (p < 0.001). Target LDL cholesterol <100 mg/dl was attained in 76% of mipomersen and 38% of placebo patients. Mipomersen also significantly reduced apolipoprotein B (-38%) and lipoprotein(a) (-24%) (p < 0.001). Common adverse events included injection site reactions (78% with mipomersen, 31% with placebo) and flu-like symptoms (34% with mipomersen, 21% with placebo). Elevations in transaminases and liver fat also occurred in some patients, and these levels returned toward baseline after treatment cessation., Conclusions: Mipomersen significantly reduced LDL cholesterol, apolipoprotein B, and lipoprotein(a) in patients with hypercholesterolemia with, or at risk for, coronary heart disease not controlled by existing therapies. (Safety and Efficacy of Mipomersen [ISIS 301012] as Add-On Therapy in High Risk Hypercholesterolemic Patients; NCT00770146)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Homozygous familial hypercholesterolaemia is a rare genetic disorder in which both LDL-receptor alleles are defective, resulting in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease. This study investigated whether an antisense inhibitor of apolipoprotein B synthesis, mipomersen, is effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with this disease., Methods: This randomised, double-blind, placebo-controlled, phase 3 study was undertaken in nine lipid clinics in seven countries. Patients aged 12 years and older with clinical diagnosis or genetic confirmation of homozygous familial hypercholesterolaemia, who were already receiving the maximum tolerated dose of a lipid-lowering drug, were randomly assigned to mipomersen 200 mg subcutaneously every week or placebo for 26 weeks. Randomisation was computer generated and stratified by weight (<50 kg vs >/=50 kg) in a centralised blocked randomisation, implemented with a computerised interactive voice response system. All clinical, medical, and pharmacy personnel, and patients were masked to treatment allocation. The primary endpoint was percentage change in LDL cholesterol concentration from baseline. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00607373., Findings: 34 patients were assigned to mipomersen and 17 to placebo; data for all patients were analysed. 45 patients completed the 26-week treatment period (28 mipomersen, 17 placebo). Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L (SD 3.6) in the mipomersen group and 10.4 mmol/L (3.7) in the placebo group. The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen (-24.7%, 95% CI -31.6 to -17.7) than with placebo (-3.3%, -12.1 to 5.5; p=0.0003). The most common adverse events were injection-site reactions (26 [76%] patients in mipomersen group vs four [24%] in placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal., Interpretation: Inhibition of apolipoprotein B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs, including high-dose statins., Funding: ISIS Pharmaceuticals and Genzyme Corporation., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Patients with type 2 diabetes mellitus have an increased risk of cardiovascular events even when treated to low-density lipoprotein (LDL) cholesterol goals. The purpose of this study was to determine how many diabetic patients with low LDL cholesterol have correspondingly low numbers of LDL particles (LDL-P) and the extent to which those achieving target levels of LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol might still harbor residual risk associated with increased LDL-P. Split-sample measurements of LDL cholesterol, non-HDL cholesterol, and nuclear magnetic resonance measured LDL-P were performed on plasma samples from 2,355 patients with type 2 diabetes seen in clinical practice and who had LDL cholesterol levels <100 mg/dl. Substantial heterogeneity of LDL-P was noted among patients with low or very low levels of LDL cholesterol. Of 1,484 patients with low LDL cholesterol (70 to 99 mg/dl), only 385 (25.9%) had low levels of LDL-P (<20th percentile of an ethnically diverse contemporary reference population), whereas 468 (31.6%) had LDL-P values >50th percentile (>1,300 nmol/L). Among the 871 patients with very low LDL cholesterol, i.e., <70 mg/dl, 349 (40.1%) had LDL-P levels >1,000 nmol/L (>20th percentile) and 91 (10.4%) had LDL-P levels >50th percentile. For patients with high triglyceride values (200 to 400 mg/dl), there was less discordance between LDL-P and non-HDL cholesterol than between LDL-P and LDL cholesterol. However, for those with triglyceride levels <200 mg/dl, LDL-P distributions were similarly wide for patients having achieved low or very low targets of LDL cholesterol or non-HDL cholesterol. In conclusion, these data demonstrate that patients with type 2 diabetes mellitus and LDL cholesterol levels <100 mg/dl are extremely heterogeneous with regard to LDL-P and, by inference, LDL-based cardiovascular risk.