scholarly journals Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Beth A. Taylor ◽  
Gregory Panza ◽  
Linda S. Pescatello ◽  
Stuart Chipkin ◽  
Daniel Gipe ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Present Report ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
High Dose ◽  
Drug Compliance ◽  
Atorvastatin Treatment ◽  
Pill Counts ◽  
And Gender

The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9) levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C) with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (ΔLDL-C: 2.6 ± 11.4%) were compared to age- and gender-matched atorvastatin responders (ΔLDL-C: 50.7 ± 8.5%) and placebo-treated subjects (ΔLDL-C: 9.9 ± 21.5%). Free PCSK9 was marginally higher in nonresponders at baseline(P=0.07)and significantly higher in atorvastatin responders after 6 months of treatment(P=0.04). The change in free PCSK9 over 6 months with statin treatment was higher(P<0.01)in atorvastatin responders (134.2 ± 131.5 ng/mL post- versus prestudy) than in either the nonresponders (39.9 ± 87.8 ng/mL) or placebo subjects (27.8 ± 97.6 ng/mL). Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment.

Drug related metabolites and genetic polymorphisms predict low low-density lipoprotein cholesterol response to atorvastatin treatment in patients with coronary heart disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Munkhaugen ◽  
E Sverre ◽  
O Kristiansen ◽  
M.W Fagerland ◽  
K Peersen ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Genetic Polymorphisms ◽  
Individual Variation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Funding Source ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Atorvastatin Treatment

Abstract Background There is considerable individual variation in the low-density lipoprotein cholesterol (LDL-C) reduction at all classes and doses of statins. Knowledge of the determinants of individual variation LDL-C response upon statin treatment may pave the way for personalized and optimized statin treatment. Purpose We aimed to determine clinical and drug related predictors of variability of LDL-C response to atorvastatin 40 mg in patients with coronary heart disease. Methods This is an explorative study among 70 patients enrolled in the MUscle Side-Effects of atorvastatin in coronary patients (MUSE) randomized double blinded cross-over trial. Absolute and relative changes in LDL-C after 7 weeks treatment with atorvastatin 40 mg/day and 7 weeks treatment with placebo, were calculated for each patient. Linear regression analyses were applied to investigate the association between clinical (10 variables) and drug related (atorvastatin and/or metabolites, 18 variables) predictors and changes in LDL-C. Results Adherence to allocated treatment was high as confirmed by atorvastatin levels in blood and a mean proportion of days covered of 99% (range 91–100%). Mean reduction in LDL-C on atorvastatin treatment (LDL-C atorvastatin – LDL-C placebo) was 2.1 (SD 0.7, range 0.3 to 3.4) mmol/L. Mean percentage reduction in LDL-C was 51.1 (SD 11.2, range 29 to 60)%, and 37 patients (52.9%) had &lt;50% LDL-C reduction. Genetic polymorphisms in SLCO1B1 or CYP3A (B 0.06, 95% CI 0.01 to 0.12, p=0.026), increasing number of coronary events (B 0.06, 95% CI 0.002 to 0.10, p=0.005), increasing trough concentration of 4-OH atorvastatin lactone (B 0.05, 95% CI 0.01 to 0.08, p=0.005) and increasing trough concentration of 4-OH atorvastatin acid (B 0.05, 95% CI 0.01 to 0.08, p=0.006) were the significant determinants of lower relative change (%) in LDL-C, in adjusted analyses. Age, gender, somatic comorbidity, cardiovascular risk factors, statin dependent muscle side-effects and other clinical and drug related determinants were not associated with changes in LDL-C. Conclusions There is considerable inter-individual variation in the LDL-C response upon treatment with atorvastatin despite confirmed high statin adherence. This is the first study reporting that genetic polymorphisms involved in the metabolism of statins and atorvastatin metabolites predict lower LDL-C response. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Association of Health, Grant/Award

Atorvastatin normalizes endothelial function in healthy smokers

2006 ◽  
Vol 111 (1) ◽  
pp. 87-91 ◽  
Author(s):  
Stefan Agewall ◽  
Åsa Hernberg
Keyword(s):  
Endothelial Function ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Control Group ◽  
Flow Mediated Dilation ◽  
Atorvastatin Treatment ◽  
Cholesterol Levels ◽  
Smoking Group ◽  
To Receive

Endothelial function is known to predict cardiovascular disease. The aim of the present study was to examine whether endothelial function in smokers with normal cholesterol levels could be normalized by treatment with 80 mg of atorvastatin in comparison with a control group. Healthy smokers (n=20) and non-smokers (n=20) were randomized to receive 80 mg of atorvastatin or placebo in an open randomized cross-over study, followed by measurement of endothelial functional [FMD (flow-mediated dilation)]. At baseline, smokers had a lower FMD compared with the non-smoking group (2.2±0.5 and 4.5±0.8% respectively; P<0.05). In the smoking group, FMD increased significantly (P<0.05) to 4.0±0.8% during treatment with atorvastatin and returned to basal levels during placebo (2.3±0.6%). In the non-smoking group, FMD was unaffected by both atorvastatin and placebo. The net change of total cholesterol or LDL (low-density lipoprotein)-cholesterol was not associated with the net change in FMD when the study group was considered as a whole or the smoking group was considered separately. In conclusion, improved endothelial function was observed in a group of smokers when they were received 80 mg of atorvastatin, whereas atorvastatin had no effect on endothelial function in the non-smoking group. The improved FMD among smokers was independent of the decrease in LDL-cholesterol during atorvastatin treatment. The results show that poor endothelial function in smokers with normal lipid levels can be improved by a statin treatment.

P6261Aortic stiffness and carotid intima thickness in hypercholesterolemic males with erectile dysfunction: relation to smoking status and statin therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Ioakeimidis ◽  
C Vlachopoulos ◽  
D Terentes-Printzios ◽  
I Koutagiar ◽  
S Pantou ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Statin Therapy ◽  
Smoking Status ◽  
Low Density Lipoprotein ◽  
Harmful Effect ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Statin Treatment ◽  
Cross Sectional

Abstract Purpose Aim of the study was to examine possible differentiation of aortic stiffness and carotid atherosclerosis among hypercholesterolemic patients with erectile dysfunction (ED) according to smoking status and statin therapy. Methods We measured carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV) in three age-matched groups of ED patients with a moderate cardiovascular risk (SCORE) and low-density lipoprotein cholesterol (LDL-C) level greater than or equal to 100 mg/dL: Smokers not receiving statin therapy (n=106), Smokers actively under statin treatment for at least three months with no dose adjustment for a minimum of six weeks (n=59) and Non-smokers not receiving statin therapy (n=97). The severity of ED was evaluated with measurements of penile peak velocity (PSV) 20 min after the intracavernous injection of prostaglandin E1 (20 μg). Results The groups of untreated smokers and non-smokers had similar mean LDL-C level. The mean LDL-C of patients under statin therapy was lower, however the differences with the level of the untreated patients was not statistically significant. Overall 33 (56%) of the patients under statin therapy reached their LDL-C goal. Body mass index and the prevalence of hypertension were not different between the three groups. The PSV was significantly lower in smokers with or without therapy compared to that of non-smokers, denoting significant influence of smoking status on the smaller in size penile arteries and consequently, a unfavorable effect on erectile function. Figure illustrates the differences in cfPWV (left plot) and cIMT (right plot) mean (±SE) values between the three groups. Smokers not receiving statin therapy had significantly higher cfPWV compared to the other groups while smokers under statin therapy had no different cfPWV than that of non-smokers not receiving therapy. The cIMT values were not different between the three groups. Smoking, statins and vascular changes Conclusions Smokers ED patients receiving statin therapy exhibited similar atherosclerotic burden compared to untreated hypercholesterolemic individuals, however, the cfPWV was significantly lower, possibly because of the known pleiotropic effects of these drugs on the aortic elastic properties. Although the cross-sectional design precludes drawing conclusions of causal relationships, the findings of this study have important clinical implications given the harmful effect of both hypercholesterolemia and smoking in men suffering from ED and the higher risk for future cardiovascular events that ED confers.

scholarly journals Ezetimibe and Improving Cardiovascular Outcomes: Current Evidence and Perspectives

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Akshyaya Pradhan ◽  
Monika Bhandari ◽  
Rishi Sethi
Keyword(s):  
Statin Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Cardiovascular Outcomes ◽  
Current Evidence ◽  
High Dose ◽  
Residual Cardiovascular Risk ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Absorption Inhibitor

Low-density lipoprotein lowering with statins has convincingly and consistently proven to reduce cardiovascular events in both primary and secondary prevention. However, despite high-dose statin therapy, residual cardiovascular risk remains and many patients also do not tolerate statins. Ezetimibe was initially projected as a frontline alternative to statin. It is an intestinal cholesterol absorption inhibitor with modest LDL lowering effects. But, major studies failed to demonstrate any beneficial effect of CV outcomes, and the drug was relegated to oblivion. IMPROVE-IT, a contemporary, large, and well-designed trial, unequivocally demonstrated reduction in CV outcomes with ezetimibe when added to statin therapy. The benefits are seen in both sexes, elderly, CKD, diabetes mellitus, and in patients with prior CABG. It also reduces biomarkers and induces plaque regression like statins. The drug has now established itself as an add-on therapy to statin when monotherapy fails to achieve LDL goals and when it is not tolerated. The combination therapy has excellent safety and efficacy record. It has now been endorsed by major guidelines too in management of dyslipidemia. Yes, ezetimibe can indeed improve cardiovascular outcomes!

scholarly journals Factors Associated with the Prescribing of High-Intensity Statins

2020 ◽  
Vol 9 (12) ◽  
pp. 3850
Author(s):  
Armando Chaure-Pardos ◽  
Sara Malo ◽  
María José Rabanaque ◽  
Federico Arribas ◽  
Belén Moreno-Franco ◽  
...  
Keyword(s):  
Statin Therapy ◽  
High Intensity ◽  
Management Practices ◽  
Characteristic Curve ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Moderate Intensity ◽  
Physically Active ◽  
Logistic Regression Models

In this study, we investigated the relationship between sociodemographic, clinical, anthropometric, and lifestyle characteristics and the type of statin prescribed for primary prevention of cardiovascular disease (CVD). We conducted an observational study in workers who began statin treatment. Statin therapy was categorized as “high-intensity” or “low–moderate-intensity”. Workers were classified according to the alignment of their statin therapy with the recommended management practices. Logistic regression models were used to evaluate the association between the different variables studied and the probability of being prescribed high-intensity statins. The only variables associated with a higher probability of being treated with high-intensity statins were increased physical activity (>40 versus <20 METs (metabolic equivalent of task) h/wk; odds ratio (OR), 1.65; 95%CI, 1.08–2.50) and, in diabetics, higher low-density lipoprotein cholesterol (LDL-C) levels (≥155 mg/dL versus <155 mg/dL; OR, 4.96; 95%CI, 1.29–19.10). The model that best predicted treatment intensity included LDL-C, diabetes, hypertension, smoking, and age (area under the Receiver Operating Characteristic curve (AUC), 0.620; 95%CI, 0.574–0.666). The prescribing and type of statin used in primary CVD prevention did not correspond with the indications in current guidelines. The probability of receiving high-intensity statins was higher in diabetics with high LDL-C levels and in more physically active individuals. These findings underscore the great variability and uncertainty in the prescribing of statins.

scholarly journals Metabolomic consequences of genetic inhibition of PCSK9 compared with statin treatment

2018 ◽  
Author(s):  
Eeva Sliz ◽  
Johannes Kettunen ◽  
Michael V Holmes ◽  
Clare Oliver-Williams ◽  
Charles Boachie ◽  
...  
Keyword(s):  
Amino Acids ◽  
Statin Therapy ◽  
Lipid Composition ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Metabolic Effects ◽  
Lipid Lowering ◽  
Low Density ◽  
Pcsk9 Inhibitors

ABSTRACTBackgroundBoth statins and PCSK9 inhibitors lower blood low-density lipoprotein cholesterol (LDL-C) levels to reduce risk of cardiovascular events. To assess potential differences between metabolic effects of these two lipid-lowering therapies, we performed detailed lipid and metabolite profiling of a large randomized statin trial, and compared the results with the effects of genetic inhibition of PCSK9, acting as a naturally occurring trial.Methods228 circulating metabolic measures were quantified by nuclear magnetic resonance spectroscopy, including lipoprotein subclass concentrations and their lipid composition, fatty acids, and amino acids, for 5,359 individuals (2,659 on treatment) in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial at 6-months post-randomization. The corresponding metabolic measures were analyzed in eight population cohorts (N=72,185) using PCSK9 rs11591147 as an unconfounded proxy to mimic the therapeutic effects of PCSK9 inhibitors.ResultsScaled to an equivalent lowering of LDL-C, the effects of genetic inhibition of PCSK9 on 228 metabolic markers were generally consistent with those of statin therapy (R2=0.88). Alterations in lipoprotein lipid composition and fatty acid balance were similar. However, discrepancies were observed for very-low-density lipoprotein (VLDL) lipid measures. For instance, genetic inhibition of PCSK9 showed weaker effects on lowering of VLDL-cholesterol compared with statin therapy (54% vs. 77% reduction, relative to the lowering effect on LDL-C; P=2 × 10−7 for heterogeneity). Genetic inhibition of PCSK9 showed no robust effects on amino acids, ketones, and a marker of inflammation (GlycA); in contrast, statin treatment lowered GlycA levels.ConclusionsGenetic inhibition of PCSK9 results in similar metabolic effects as statin therapy across a detailed lipid and metabolite profile. However, for the same lowering of LDL-C, PCSK9 inhibitors are predicted to be less efficacious than statins at lowering VLDL lipids, which could potentially translate into subtle differences in cardiovascular risk reduction.

Abstract 257: Pilot Study of the Safety and Feasibility of the Treatment of Paclitaxel Associated to a Cholesterol-Rich Nanoemulsion in Patients With Aortic Atherosclerotic Disease

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Raul C Maranhao ◽  
Afonso A Shiozaki ◽  
Tiago Senra ◽  
Aleksandra T Morikawa ◽  
Debora F Deus ◽  
...  
Keyword(s):  
Pilot Study ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pharmacological Action ◽  
Statin Treatment ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Aged Patients ◽  
Atherosclerotic Lesions ◽  
Aortic Artery

Previously, we showed that the toxicity of chemotherapeutic agents used in cancer treatment can be drastically reduced by association to nanoemulsions (LDE) that mimic the lipid composition of low-density lipoprotein (LDL), without loss of pharmacological action. Injected into the circulation, LDE concentrates associated drugs, such as the anti-proliferative agent paclitaxel, in neoplastic tissues and in atherosclerotic lesions. In rabbits with atherosclerosis lesions were reduced by 65% by LDE-paclitaxel treatment. Tolerability and safety of high dose LDE-paclitaxel was shown in several patients with advanced cancers. Based on those findings, this pilot study was designed to test, in 9 aged patients with extensive aortic atherosclerosis, LDE-paclitaxel at 175 mg/m2 body surface dose (I.V., 3/3 weeks for 6 cycles). All were under statin treatment that was not discontinued during the 18-week treatment period. No observable clinical or laboratorial toxicity was observed. One death occurred but was unrelated with treatment toxicity. Images acquired by Multiple Detector Computer Tomography Angiography (64-slice scanner) taken before and at 2-3 month after the treatment end showed that the mean volume of the aortic artery wall was clearly reduced in 4 of the 8 patients, while in 3 it remained unchanged and in one it clearly increased. Therefore, the treatment was tolerable for patients with cardiovascular disease and these results encourage large, placebo-controlled clinical studies to ascertain the ability of LDE-paclitaxel to reduce atherosclerotic lesions.

Abstract 3763: Standard-dose Statin Therapy Demonstrates Additional Effects In Diabetic Patients With Normal Cholesterol Levels

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sunao Kojima ◽  
Tomohiro Sakamoto ◽  
Akira Kitagawa ◽  
Hisao Ogawa
Keyword(s):  
Statin Therapy ◽  
Standard Dose ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coronary Intervention ◽  
Statin Treatment ◽  
Pleiotropic Effect ◽  
Diabetic Patients ◽  
Cholesterol Levels ◽  
Patients With Diabetes

Background: Randomized trials established statins as an agent for prevention of coronary heart disease (CHD). We assessed the hypothesis that standard-dose statin therapy had a beneficial effect in diabetic CHD patients with normal cholesterol levels. Methods and Results: To evaluate the effect of statins after percutaneous coronary intervention (PCI) on subsequent cardiovascular events, a prospective, randomized, open, blinded-endpoint trial conducted from 2002 to 2004 at 55 hospitals in Japan. A total of 1,016 patients (301 patients with diabetes mellitus [DM] and 715 non-DM patients) whose total cholesterol levels ranged from 180 to 240 mg/dL was enrolled and randomly assigned to receive any available standard-dose statins within 96 hours after PCI. Clinical parameters were comparable between DM group and non-DM group. The low-density lipoprotein cholesterol (LDL-C) levels were equally decreased after statin treatment in 2 groups (Table ). However, event rate for the primary end point was particularly lower in DM patients with statin treatment than those without statin treatment (Figure). Conclusions: Standard-dose statin therapy provides incremental clinical benefit in DM patients with normal cholesterol levels compared with that in non-DM patients. These data suggest that DM patients derive pleiotropic effect from statins, irrespective of lowering effect of LDL-C levels. Serial changes of LDL cholesterol levels

Have we learnt all from IMPROVE-IT? Part II. Subanalyses on the ef- fects of ezetimibe added to statin therapy on selected clinical and laborato- ry outcomes, cost effectiveness, guideline and clinical implications

2020 ◽  
Vol 18 ◽  
Author(s):  
Zlatko Fras ◽  
Dimitri P. Mikhailidis
Keyword(s):  
Statin Therapy ◽  
Artery Bypass ◽  
Low Density Lipoprotein ◽  
Bypass Graft ◽  
Density Lipoprotein ◽  
Drug Discontinuation ◽  
Atherosclerotic Cardiovascular Disease ◽  
History Of ◽  
Risk Cost ◽  
Cardiovascular Biomarkers

: In this second part of a review of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), we discuss the findings in relation to patients with stroke, the ACS phenotype, history of coronary artery bypass graft surgery, heart failure, concurrent polyvascular atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus, and different levels of expression of selected cardiovascular biomarkers. The combination therapy was proven safe, and drug discontinuation rates were not increased by adding ezetimibe. Since both statins and ezetimibe are now almost globally generically available, we can conclude that for secondary prevention of ASCVD, adding ezetimibe to high-intensity statin therapy further reduces low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk cost-effectively.

Efficacy and Safety of Evolocumab in Reducing Low Density Lipoprotein Cholesterol Levels in Chinese Patients with Non-ST-segment Elevation Acute Coronary Syndrome

2020 ◽  
Vol 18 ◽  
Author(s):  
Xiaohan Xu ◽  
Meng Chai ◽  
Yujing Cheng ◽  
Pingan Peng ◽  
Xiaoli Liu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Chinese Patients ◽  
Lipid Lowering ◽  
Control Group ◽  
Lipid Lowering Therapy ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
St Segment

Aims: To explore early intensive lipid-lowering therapy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels can reduce cardiovascular morbidity and mortality in patients with atherosclerotic cardiovascular disease. Due to many reasons, the need for early intensive lipid-lowering therapy is far from being met in Chinese NSTE-ACS patients at high-risk of recurrent ischaemic events. Objective: To evaluate the feasibility, safety and efficacy of starting evolocumab in hospital to lower LDL-C levels in Chinese patients with NSTE-ACS. Methods: In this prospective cohort study initiated by researchers, 334 consecutive patients with NSTE-ACS who had sub-standard LDL-C levels (LDL-C ≥2.3 mmol/L after regular oral statin treatment for at least 4 weeks; or LDL-C ≥3.2 mmol/L without regular oral statin treatment) were included. Patients who agreed to treatment with evolocumab (140 mg subcutaneously every 2 weeks, initiated in hospital and used for 12 weeks after discharge) were enrolled in the evolocumab group (n=96) and others in the control group (n=238). All enrolled patients received regular statin treatment (atorvastatin 20 mg/day or rosuvastatin 10 mg/day; doses unchanged throughout the study).The primary endpoint was the change in LDL-C levels from baseline to week 12. Results: Most patients (67.1%) had not received regular statin treatment before. In the evolocumab group, LDL-C levels decreased significantly at week 4 and remained stable at week 8 and 12 (all p<0.001). At week 12, the LDL-C percentage change from baseline in the evolocumab group was -79.2±12.7% (from an average of 3.7 to 0.7 mmol/L), while in the control group it was -37.4±15.4% (from an average of 3.3 to 2.0 mmol/L). The mean difference between these 2 groups was -41.8% (95% CI -45.0 to -38.5%; p<0.001). At week 12, the proportions of patients with LDL-C levels <1.8 mmol/L and 1.4 mmol/L in the evolocumab group were significantly higher than in the control group (96.8 vs 36.1%; 90.6 vs 7.1%; both p<0.001). The incidence of adverse events and cardiovascular events was similar in both groups. Conclusions: In this prospective cohort study we evaluated the early initiation of evolocumab in NSTE-ACS patients in China. Evolocumab combined with statins significantly lowered LDL-C levels and increased the probability of achieving recommended LDL-C levels, with satisfactory safety and well tolerance.

Sign in / Sign up

Export Citation Format

Share Document