Most cited article - PubMed ID 28859947
Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial
INTRODUCTION: This survey aims to assess the implementation of recommendations from the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) by clinical biochemistry laboratories in Czechia and Slovakia in their policies for reporting low-density lipoprotein cholesterol (LDL-C) concentrations. MATERIALS AND METHODS: The web-based survey was distributed to all 383 Czech and Slovak clinical biochemistry laboratories that measure lipids by external quality assessment provider SEKK. A total of 17 single-answer questions were included. The questionnaire was focused on the detection and decision points in familial hypercholesterolemia (FH). All survey answers were taken into account. The laboratories followed the EFLM and EAS guidelines when they reported an interpretative comment considering FH diagnosis in adults. RESULTS: A total of 203 (53%) laboratories answered. Only 5% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 5.0 mmol/L in adults, and 3% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 4.0 mmol/L in children. Only 7% of laboratories reported goals for all cardiovascular risk categories (low, moderate, high, very high). Non-HDL cholesterol concentrations were calculated by 74% of responders. A significant number (51%) of participants did not measure apolipoprotein B, and 59% of laboratories did not measure lipoprotein(a). CONCLUSIONS: Only a small portion of laboratories from Czechia and Slovakia reported high LDL-C results with interpretative comments considering FH diagnosis in adults, the laboratories did not follow the guidelines.
- Keywords
- HDL cholesterol, LDL cholesterol, apolipoprotein B, familial hypercholesterolemia, lipoprotein(a), technical report,
- MeSH
- Atherosclerosis * MeSH
- Cholesterol MeSH
- Child MeSH
- Adult MeSH
- Hyperlipoproteinemia Type II * diagnosis MeSH
- Laboratories MeSH
- Cholesterol, LDL MeSH
- Humans MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Slovakia MeSH
- Names of Substances
- Cholesterol MeSH
- Cholesterol, LDL MeSH
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. Despite the clinical long-term and near-term benefits of lowering cholesterol in, respectively, primary and secondary prevention of ASCVD, cholesterol levels remain under-treated, with many patients not achieving their recommended targets. The present article will review the latest updates on lipid management with emphases on the different classes of cholesterol-lowering agents and their clinical uses.
- Keywords
- ASCVD, Atherosclerotic cardiovascular disease, Cholesterol, Lipid management, Triglycerides,
- MeSH
- Anticholesteremic Agents adverse effects therapeutic use MeSH
- Atherosclerosis blood diagnosis drug therapy mortality MeSH
- Biomarkers blood MeSH
- Cholesterol blood MeSH
- Risk Reduction Behavior MeSH
- Exercise MeSH
- Dyslipidemias blood diagnosis drug therapy mortality MeSH
- Humans MeSH
- Protective Factors MeSH
- Risk Factors MeSH
- Triglycerides blood MeSH
- Treatment Outcome MeSH
- Diet, Healthy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Anticholesteremic Agents MeSH
- Biomarkers MeSH
- Cholesterol MeSH
- Triglycerides MeSH
IMPORTANCE: Recent studies have shown that Friedewald underestimates low-density lipoprotein cholesterol (LDL-C) at lower levels, which could result in undertreatment of high-risk patients. A novel method (Martin/Hopkins) using a patient-specific conversion factor provides more accurate LDL-C levels. However, this method has not been tested in proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor-treated patients. OBJECTIVE: To investigate accuracy of 2 different methods for estimating LDL-C levels (Martin/Hopkins and Friedewald) compared with gold standard preparative ultracentrifugation (PUC) in patients with low LDL-C levels in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk (FOURIER) trial. DESIGN, SETTING, AND PARTICIPANTS: The FOURIER trial was a randomized clinical trial of evolocumab vs placebo added to statin therapy in 27 564 patients with stable atherosclerotic cardiovascular disease. The patients' LDL-C levels were assessed at baseline, 4 weeks, 12 weeks, 24 weeks, and every 24 weeks thereafter, and measured directly by PUC when the level was less than 40 mg/dL per the Friedewald method (calculated as non-HDL-C level - triglycerides/5). In the Martin/Hopkins method, patient-specific ratios of triglycerides to very low-density lipoprotein cholesterol (VLDL-C) ratios were determined and used to estimate VLDL-C, which was subtracted from the non-HDL-C level to obtain the LDL-C level. MAIN OUTCOMES AND MEASURES: Low-density lipoprotein cholesterol calculated by the Friedewald and Martin/Hopkins methods, with PUC as the reference method. RESULTS: For this analysis, the mean (SD) age was 62.7 (9.0) years; 2885 of the 12 742 patients were women (22.6%). A total of 56 624 observations from 12 742 patients had Friedewald, Martin/Hopkins, and PUC LDL-C measurements. The median difference from PUC LDL-C levels for Martin/Hopkins LDL-C levels was -2 mg/dL (interquartile range [IQR], -4 to 1 mg/dL) and for Friedewald LDL-C levels was -4 mg/dL (IQR, -8 to -1 mg/dL; P < .001). Overall, 22.9% of Martin/Hopkins LDL-C values were more than 5 mg/dL different than PUC values, and 2.6% were more than 10 mg/dL different than PUC levels. These were significantly less than respective proportions with Friedewald estimation (40.1% and 13.3%; P < .001), mainly because of underestimation by the Friedewald method. The correlation with PUC LDL-C was significantly higher for Martin/Hopkins vs Friedewald (ρ, 0.918 [95% CI 0.916-0.919] vs ρ, 0.867 [0.865-0.869], P < .001). CONCLUSIONS AND RELEVANCE: In patients achieving low LDL-C with PCSK9 inhibition, the Martin/Hopkins method for LDL-C estimation more closely approximates gold standard PUC than Friedewald estimation does. The Martin/Hopkins method may prevent undertreatment because of LDL-C underestimation by the Friedewald method. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01764633.
- MeSH
- Anticholesteremic Agents therapeutic use MeSH
- Atherosclerosis blood drug therapy MeSH
- Cholesterol, HDL analysis blood MeSH
- Risk Assessment MeSH
- Antibodies, Monoclonal, Humanized MeSH
- Hyperlipidemias blood drug therapy MeSH
- Cholesterol, LDL analysis blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- Randomized Controlled Trials as Topic MeSH
- Aged MeSH
- Statistics as Topic methods MeSH
- Triglycerides analysis blood MeSH
- Ultracentrifugation methods MeSH
- Cholesterol, VLDL analysis blood MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Anticholesteremic Agents MeSH
- evolocumab MeSH Browser
- Cholesterol, HDL MeSH
- Antibodies, Monoclonal, Humanized MeSH
- Cholesterol, LDL MeSH
- Antibodies, Monoclonal MeSH
- Triglycerides MeSH
- Cholesterol, VLDL MeSH