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9 záznamů v Medvik Filtry

Článek

Comparison of Low-Density Lipoprotein Cholesterol Assessment by Martin/Hopkins Estimation, Friedewald Estimation, and Preparative Ultracentrifugation: Insights From the FOURIER Trial

Martin, Seth S
Autor Martin, Seth S Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Giugliano, Robert P
Autor Giugliano, Robert P Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts
Murphy, Sabina A
Autor Murphy, Sabina A Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts
Wasserman, Scott M
Autor Wasserman, Scott M Amgen, Thousand Oaks, California
Stein, Evan A
Autor Stein, Evan A Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio
Ceška, Richard
Autor Ceška, Richard Center of Preventive Cardiology, 3rd Department Internal Medicine, University General Hospital and First Medical Faculty, Prague, Czech Republic
López-Miranda, José
Autor López-Miranda, José Lipids and Atherosclerosis Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofía University Hospital, University of Cordoba, Cordoba, Spain. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObN), Cordoba, Spain
Georgiev, Borislav
Autor Georgiev, Borislav Department of Cardiology, National Heart Hospital, Sofia, Bulgaria
Lorenzatti, Alberto J
Autor Lorenzatti, Alberto J Cardiology Department, Cordoba Hospital, Cordoba, Argentina
Tikkanen, Matti J
Autor Tikkanen, Matti J Folkhälsan Research Center, University of Helsinki, Helsinki, Finland

JAMA cardiology. 2018 ; 3 (8) : 749-753. [pub] 20180801

JAMA Cardiol
ISSN 2380-6591
Medvik
Zdroj

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
anticholesteremika terapeutické užití MeSH
ateroskleróza krev farmakoterapie MeSH
HDL-cholesterol analýza krev MeSH
hodnocení rizik MeSH
humanizované monoklonální protilátky MeSH
hyperlipidemie krev farmakoterapie MeSH
LDL-cholesterol analýza krev MeSH
lidé středního věku MeSH
lidé MeSH
monoklonální protilátky terapeutické užití MeSH
randomizované kontrolované studie jako téma MeSH
senioři MeSH
statistika jako téma metody MeSH
triglyceridy analýza krev MeSH
ultracentrifugace metody MeSH
VLDL-cholesterol analýza krev MeSH
Check Tag
lidé středního věku MeSH
lidé MeSH
mužské pohlaví MeSH
senioři MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
srovnávací studie MeSH

Článek

Budoucí úloha inhibitorů proprotein-konvertázy subtilisin/kexin 9 v léčbě hyperlipidémie

Stein, Evan A
Autor Stein, Evan A Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio, USA

Current Opinion in Endocrinology, Diabetes and Obesity (České vyd.). 2016 ; 4 (2) : 31-38.

Curr. Opin. Endocrinol. Diabetes Obes. (Čes. vyd.)
ISSN 1805-7101
Medvik
Zdroj

MeSH
biologické markery krev MeSH
cílená molekulární terapie MeSH
hyperlipidemie diagnóza enzymologie farmakoterapie krev MeSH
hypolipidemika terapeutické užití MeSH
inhibitory serinových proteinas farmakokinetika škodlivé účinky terapeutické užití MeSH
lidé MeSH
lipidy krev MeSH
monoklonální protilátky terapeutické užití MeSH
objevování léků MeSH
PCSK9 inhibitory MeSH
proproteinkonvertasa subtilisin/kexin typu 9 metabolismus MeSH
výsledek terapie MeSH
Check Tag
lidé MeSH
mužské pohlaví MeSH
Publikační typ
přehledy MeSH

Článek

Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial

JAMA (Chicago, Ill.). 2016 ; 315 (15) : 1580-90.

JAMA
ISSN 1538-3598
Medvik
Zdroj

IMPORTANCE: Muscle-related statin intolerance is reported by 5% to 20% of patients. OBJECTIVE: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. DESIGN, SETTING, AND PARTICIPANTS: Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. INTERVENTIONS: Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). MAIN OUTCOME AND MEASURES: Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels. RESULTS: Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7% (95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, -54.5% (95% CI, -57.2% to -51.8%); absolute change, -106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, -31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, -52.8% (95% CI, -55.8% to -49.8%); absolute change, -102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was -37.8%; absolute difference, -75.8 mg/dL. For week 24, between-group difference in LDL-C was -36.1%; absolute difference, -71.7 mg/dL. Muscle symptoms were reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%). CONCLUSIONS AND RELEVANCE: Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01984424.

Článek

A 52-week placebo-controlled trial of evolocumab in hyperlipidemia

The New England journal of medicine. 2014 ; 370 (19) : 1809-19.

N Engl J Med
ISSN 1533-4406
Medvik
Zdroj

BACKGROUND: Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS: We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS: Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS: At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks. (Funded by Amgen; DESCARTES ClinicalTrials.gov number, NCT01516879.).

Článek

Snižování koncentrace LDL cholesterolu a prevence kardiovaskulárních onemocnění
[Low-density lipoprotein cholesterol reduction and prevention of cardiovascular disease]

Stein, Evan A
Autor Stein, Evan A

Medicína po promoci. 2009 ; 10 (3) : 12-15.

ISSN 1212-9445
Medvik
Zdroj

April issue of Mayo Clinic Proceedings, two articles discuss lipid lowering and prevention of cardiovascular disease (CVD). Karalis reviews and evaluates the evidence supporting a low-density lipoprotein cholesterol (LDL-C) target of less than 100 mg/dL for moderately high-risk individuals and concludes by saying, “The current evidence supports a strategy of early and aggressive lowering of LDL-C levels for the primary prevention of CAD [coronary artery disease].” Al Badarin et al review the published literature on the effect of LDL-C by cholesterol absorption transport inhibition with ezetimibe. They conclude correctly that even though ezetimibe lowers LDL-C levels, reduces circulating inflammatory biomarkers like high-sensitivity C-reactive protein when added to statins, and has a variable effect on endothelial function based on a few small studies, no randomized controlled trial (RCT) has shown evidence of its impact on prevention of cardiovascular events.