scholarly journals Lipid Lowering Treatment and Eligibility for PCSK9 Inhibition in Post-Myocardial Infarction Patients in Italy: Insights from Two Contemporary Nationwide Registries

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Furio Colivicchi ◽  
Michele Massimo Gulizia ◽  
Marcello Arca ◽  
Pier Luigi Temporelli ◽  
Lucio Gonzini ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Regulatory Agency ◽  
Stable Coronary Artery Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
High Dose ◽  
Study Cohort ◽  
Pcsk9 Inhibitors ◽  
European Society Of Cardiology

Introduction. The current use of lipid lowering therapies and the eligibility for proprotein convertase subtilisin/kexin-9 (PCSK9) inhibitors of patients surviving a myocardial infarction (MI) is poorly known. Methods. Using the data from two contemporary, nationwide, prospective, real-world registries of patients with stable coronary artery disease, we sought to describe the lipid lowering therapies prescribed by cardiologists in patients with a prior MI and the resulting eligibility for PCSK9 inhibitors according to the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) and the Italian regulatory agency (Agenzia Italiana del Farmaco; AIFA) criteria. The study cohort was stratified according to the following low-density lipoprotein cholesterol (LDL-C) levels at the time of enrolment: <70 mg/dl; 70–99 mg/dl and ≥100 mg/dl. Results. Among the 3074 post-MI patients with LDL-C levels available, a target level of LDL-C < 70 mg/dl was present in 1186 (38.6%), while 1150 (37.4%) had LDL-C levels ranging from 70 to 99 mg/dl and the remaining 738 (24.0%) an LDL-C ≥ 100 mg/dl. A statin was prescribed more frequently in post-MI patients with LDL-C levels <70 mg/dl (97.1%) compared to the other LDL-C groups (p<0.0001). A low dose of statin was prescribed in 9.3%, while a high dose in 61.4% of patients. Statin plus ezetimibe association therapy was used in less than 18% of cases. In the overall cohort, 293 (9.8%) and 450 (22.2%) resulted eligible for PCSK9 inhibitors, according to ESC/EAS and AIFA criteria, respectively. Conclusions. Post-MI patients are undertreated with conventional lipid lowering therapies. A minority of post-MI patients would be eligible to PCSK9 inhibitors according to ESC/EAS guidelines and Italian regulatory agency criteria.

scholarly journals Application of the 2019 ESC/EAS dyslipidaemia guidelines to nationwide data of patients with a recent myocardial infarction: a simulation study

2020 ◽  
Vol 41 (40) ◽  
pp. 3900-3909 ◽  
Author(s):  
Ali Allahyari ◽  
Tomas Jernberg ◽  
Emil Hagström ◽  
Margrét Leosdottir ◽  
Pia Lundman ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Intensity ◽  
Low Density Lipoprotein ◽  
Monte Carlo Model ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Recent Myocardial Infarction ◽  
Lowering Therapy

Abstract Aims To estimate the proportion of patients with a recent myocardial infarction (MI) who would be eligible for additional lipid-lowering therapy according to the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias, and to simulate the effects of expanded lipid-lowering therapy on attainment of the low-density lipoprotein cholesterol (LDL-C) target as recommended by the guidelines. Methods and results Using the nationwide SWEDEHEART register, we included 25 466 patients who had attended a follow-up visit 6–10 weeks after an MI event, 2013–17. While most patients (86.6%) were receiving high-intensity statins, 82.9% of the patients would be eligible for expanded lipid-lowering therapy, as they had not attained the target of an LDL-C level of &lt;1.4 mmol and a ≥50% LDL-C level reduction. When maximized use of high-intensity statins followed by add-on therapy with ezetimibe was simulated using a Monte Carlo model, the LDL-C target was reached in 19.9% using high-intensity statin monotherapy and in another 28.5% with high-intensity statins and ezetimibe, while 50.7% would still be eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. When use of alirocumab or evolocumab was simulated in those who were eligible for PCSK9 inhibitors, around 90% of all patients attained the LDL-C target. Conclusion  Our study suggests that, even with maximized use of high-intensity statins and ezetimibe, around half of patients with MI would be eligible for treatment with PCSK9 inhibitors according to the 2019 ESC/EAS guidelines. Considering the current cost of PCSK9 inhibitors, the financial implications of the new guidelines may be substantial.

Effects of Lipid Lowering Drugs on Arterial Stiffness: One More Way to Reduce Cardiovascular Risk?

2019 ◽  
Vol 18 (1) ◽  
pp. 38-42 ◽  
Author(s):  
Andromachi Reklou ◽  
Niki Katsiki ◽  
Asterios Karagiannis ◽  
Vasilios Athyros
Keyword(s):  
Arterial Stiffness ◽  
Beneficial Effect ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
High Dose ◽  
Pcsk9 Inhibitors ◽  
Vascular Events ◽  
Lipid Lowering Drugs ◽  
Meta Analyses

Arterial stiffness (AS) is considered an independent predictor of cardiovascular disease (CVD) events. Among lipid lowering drugs, statins have a beneficial effect on AS, independent of their hypolipidaemic effect. Based on 3 meta-analyses and other studies, this effect is compound- and doserelated. Potent statins at high doses are more effective than less powerful statins. Ezetimibe (± statin) also seems to decrease AS in patients with dyslipidaemia. Fibrates have no effect on AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have data that beneficially affect all AS risk factors, suggesting a beneficial effect on artery compliance. However, there is no direct measurement of their effect on AS indices. In patients with dyslipidaemia, prescribing high dose statins (± ezetimibe) will not only decrease low-density lipoprotein cholesterol levels but also improve AS (in addition to other effects). This effect on AS may contribute to the observed reduction in vascular events.

scholarly journals Evaluation of two highly effective lipid-lowering therapies in subjects with acute myocardial infarction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aline Klassen ◽  
Andrea Tedesco Faccio ◽  
Carolina Raissa Costa Picossi ◽  
Priscilla Bento Matos Cruz Derogis ◽  
Carlos Eduardo dos Santos Ferreira ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density Lipoprotein Cholesterol ◽  
Residual Cardiovascular Risk ◽  
St Segment Elevation ◽  
Lipidomic Analysis ◽  
St Segment ◽  
Highly Effective

AbstractFor cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg QD or simvastatin 40 mg combined with ezetimibe 10 mg QD for 30 days. Fasting blood samples were collected on the first day (D1) and after 30 days (D30). Lipidomic analysis was performed using the Lipidyzer platform. Similar classic lipid profile was obtained in both groups of lipid-lowering therapies. However, differences with the lipidomic analysis were observed between D30 and D1 for most of the analyzed classes. Differences were noted with lipid-lowering therapies for lipids such as FA, LPC, PC, PE, CE, Cer, and SM, notably in patients treated with rosuvastatin. Correlation studies between classic lipid profiles and lipidomic results showed different information. These findings seem relevant, due to the involvement of these lipid classes in crucial mechanisms of atherosclerosis, and may account for residual cardiovascular risk.Randomized clinical trial: ClinicalTrials.gov, NCT02428374, registered on 28/09/2014.

scholarly journals Evaluation of Lipid Lowering Effect of Milk Thistle (Silybum Marianum) in Comparison with Rosuvastatin in Rats by Using Ace-alera® Analyzer

2020 ◽  
Vol 14 ◽  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Lowering ◽  
Control Group ◽  
Milk Thistle ◽  
High Dose ◽  
Hypolipidemic Effect ◽  
Low Density ◽  
Therapeutic Protocols

Dyslipidemia is a metabolic disorder that is characterized with an elevation in the cholesterol serum levels that can be treated with various hypolipidemic drugs like rosuvastatin. The present study was undertaken to determine and evaluate the hypolipidemic effect of milk thistle seeds extract in comparison with rosuvastatin and the combination of both for the treatment of dyslipidemia in rats. Also its effect on blood glucose levels on experimentally induced dyslipidemic rats. In vivo studies were conducted on wister albino laboratory rats, in which 49 rats were induced to be dyslipidemic by a daily intragastric administration of cholesterol (2 g/kg). The induction of dyslipidemia was evaluated by comparing these rats with a negative control group that was composed of 10 healthy rats. Then, after one month dyslipidemia was induced in 49 rats that were divided into 6 groups, as the following; positive control group (n=9) received cholesterol (2 g/kg) for another one month, and the other five groups each of 8 rats continued to receive cholesterol (2 g/kg) for one month along with therapy as; rosuvastatin low dose (RL) group received 10 mg/kg, rosuvastatin high dose (RH) group received 20 mg/kg, milk thistle (MT) group received 7.15 mg/kg, (RL+MT) group received a combination of 10 mg/kg of rosuvastatin and 7.15 mg/kg of milk thistle, and (RH+MT) group received a combination of 20 mg/kg of rosuvastatin and 7.15 mg/kg of milk thistle. The statistical results of biochemical analysis showed that all the studied therapeutic protocols whether given alone; RL, RH, and MT or in a combination; RL+MT and RH+MT led to a significant (p≤0.05) hypolipidemic effect that reduced the total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) and increased the high density lipoprotein (HDL) cholesterol levels. In conclusion, all therapeutic protocols were effective in treating dyslipidemia, as they all reduced the TC, TG, LDL, and VLDL, and increased the HDL cholesterol significantly (p≤0.05). Furthermore, we found that milk thistle can be used in the management of dyslipidemia, as it has a hypolipidemic effect. Also, the addition of milk thistle to rosuvastatin therapy reduced the risk of developing diabetes mellitus (DM), as it has a glucose modulating activity either when it was given alone or in combination with rosuvastatin. Moreover, the combination of milk thistle and rosuvastatin was of a great benefit, as it gave an intensive goal of therapy than each one alone in altering all lipid profile parameters.

P829The impact of APOC3 and APOE gene polymorphisms on response to statin therapy in acute myocardial infarction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Teterina ◽  
A Geraskin ◽  
P Potapov ◽  
L Babaeva ◽  
A Pisaryuk ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Statin Therapy ◽  
Gene Polymorphisms ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Genetic Studies ◽  
Apoc3 Gene ◽  
Pronounced Reduction

Abstract Background and aim Many genetic studies have been reported about the association between APOE, APOC3 gene polymorphisms and response to statin therapy in myocardial infarction, but results remain controversial. The aim of this study was to investigate the association between SNP rs7412 (APOE), rs2854117 (APOC3), rs2854116 (APOC3) and lipid-lowering effect of atorvastatin and rosuvastatin in patients with myocardial infarction. Methods Polymorphism of genes APOE (rs7412), APOC3 (rs2854117 and rs2854116) was determened. Lipid profile was determined on admission and after 1 year of treatment. Results 78 patients with myocardial infarction treated with maximal tolerated dose of atorvastatin or rosuvastatin were included. More pronounced reduction of lipid levels was associated with of T allele of rs7412 (APOE), p<0,05. ANOVA demonstrated greater low-density lipoprotein and total cholesterol decrease in patients with combination of genes CT/TT (rs7412, APOE) and CC (rs2854117, APOC3) genotypes, CT/TT (rs7412, APOE) and CT (rs2854116, APOC3) genotypes. Conclusion The genetic variants of APOC3 and APOE are useful markers and can be use to predict response to lipid-lowering therapy with statin in myocardial infarction.

scholarly journals The history of proprotein convertase subtilisin kexin-9 inhibitors and their role in the treatment of cardiovascular disease

2020 ◽  
Vol 11 ◽  
pp. 204062232092456
Author(s):  
Eun Ji Kim ◽  
Anthony S. Wierzbicki
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Lipid Lowering ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Activating Mutations ◽  
History Of ◽  
New Guidelines

A consensus has formed based on epidemiological studies and clinical trials that intervention to reduce low density lipoprotein cholesterol (LDL-C) will reduce cardiovascular disease (CVD) events. This has progressively reduced the thresholds for intervention and targets for treatment. Whist statins are sufficient for many people in primary prevention, they only partially achieve the newer targets of secondary prevention for established CVD. Increasing use of statins has highlighted that 1–2% cannot tolerate these drugs. Other cholesterol-lowering drugs such as ezetimibe add to the benefits of statins but have limited efficacy. The discovery of activating mutations in proprotein convertase subtilisin kexin-9 (PCSK9) as a cause of familial hypercholesterolaemia while inactivating mutations lower LDL-C led to the idea to develop PCSK9 inhibitors as drugs. This article reviews the history of lipid-lowering therapies, the discovery of PCSK9 and the development of PCSK9 inhibitors. It reviews the key trials of the current antibody-based drugs and how these have influenced new guidelines. It also reviews the controversy caused by their cost and the increasing application of health economics to determine the optimum strategy for implementation of novel therapeutic pathways and surveys other options for targeting PCSK9 as well as other LDL-C lowering compounds in late development.

scholarly journals The Role of Lipid-Lowering Treatment in the Secondary Prevention of Ischemic Stroke

Diseases ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Alexandra Tsankof ◽  
Konstantinos Tziomalos
Keyword(s):  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Pcsk9 Inhibitors ◽  
Stroke Treatment ◽  
Icosapent Ethyl ◽  
History Of ◽  
Coronary Events

Dyslipidemia is a major modifiable risk factor for ischemic stroke. Treatment with statins reduces the incidence of recurrent ischemic stroke and also reduces coronary events in patients with a history of ischemic stroke. Therefore, statins represent an important component of secondary prevention of ischemic stroke. In patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets despite treatment with the maximal tolerated dose of a potent statin, ezetimibe should be added to their lipid-lowering treatment and also appears to reduce the risk of cardiovascular events. Selected patients who do not achieve LDL-C targets despite statin/ezetimibe combination are candidates for receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Finally, it appears that adding icosapent ethyl might also reduce cardiovascular morbidity in patients who have achieved LDL-C targets but have persistently elevated triglyceride levels.

Importance of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the treatment of dyslipidemia and atherosclerosis

2019 ◽  
pp. 40-52
Author(s):  
Maksim Maksimov ◽  
Anastasia Shikaleva ◽  
Aleksandra Kuchaeva
Keyword(s):  
Clinical Studies ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Pcsk9 Inhibitors ◽  
Lipid Lowering Drugs ◽  
Antibody Preparations

Representatives of different groups of lipid-lowering drugs may have some differences in the nature and severity of the effect on the blood lipid spectrum. A new class of drugs, PCSK9 inhibitors, whose activity is associated with a protein involved in the control of low density lipoprotein receptors, has recently appeared. In clinical practice, this group is represented by monoclonal antibody preparations evolocumab and alirocumab. PCSK9 inhibitors are promising drugs for use in combination lipid-lowering therapy, which so far, given the results of clinical studies, can be recommended in the third place after statins and ezetimibe. In clinical studies, it was shown that alirocoumab and evolocumab alone or in combination with statins and/or other lipid-lowering drugs significantly reduce cholesterol levels in low density lipoproteins – by an average of 60%, depending on the dose.

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