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.

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.

Statin-based therapy for primary and secondary prevention of ischemic stroke: A meta-analysis and critical overview

2019 ◽  
Vol 15 (4) ◽  
pp. 377-384 ◽  
Author(s):  
Haralampos Milionis ◽  
George Ntaios ◽  
Eleni Korompoki ◽  
Konstantinos Vemmos ◽  
Patrik Michel
Keyword(s):  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Primary And Secondary Prevention ◽  
Prevention Trials

Background and aims To reassess the effect of statin-based lipid-lowering therapy on ischemic stroke in primary and secondary prevention trials with regard to achieved levels of low-density lipoprotein-cholesterol in view of the availability of novel potent hypolipidemic agents. Methods English literature was searched (up to November 2018) for publications restricted to trials with a minimum enrolment of 1000 and 500 subjects for primary and secondary prevention, respectively, meeting the following criteria: adult population, randomized controlled design, and recorded outcome data on ischemic stroke events. Data were meta-analyzed and curve-estimation procedure was applied to estimate regression statistics and produce related plots. Results Four primary prevention trials and four secondary prevention trials fulfilled the eligibility criteria. Lipid-lowering therapy was associated with a lower risk of ischemic stroke in primary (risk ratio, RR 0.70, 95% confidence interval, CI, 0.60–0.82; p < 0.001) and in the secondary prevention setting (RR 0.80, 95% CI 0.70–0.90; p < 0.001). Curve-estimation procedure revealed a linear relationship between the absolute risk reduction of ischemic stroke and active treatment-achieved low-density lipoprotein-cholesterol levels in secondary prevention (adjusted R-square 0.90) in support of “the lower the better” hypothesis for stroke survivors. On the other hand, the cubic model followed the observed data well in primary prevention (adjusted R-square 0.98), indicating greater absolute risk reduction in high-risk cardiovascular disease-free individuals. Conclusions Statin-based lipid-lowering is effective both for primary and secondary prevention of ischemic stroke. Most benefit derives from targeting disease-free individuals at high cardiovascular risk, and by achieving low treatment targets for low-density lipoprotein-cholesterol in stroke survivors.

scholarly journals Effectiveness of more strict managements after achievement of standard target value of low-density lipoprotein cholesterol in secondary prevention of Japanese patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Endo ◽  
Y Kagawa ◽  
H Sato ◽  
Y Morita ◽  
H Kawahara ◽  
...  
Keyword(s):  
Secondary Prevention ◽  
Coronary Revascularization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Japanese Patients ◽  
Cardiac Ischemia ◽  
Low Density Lipoprotein Cholesterol ◽  
Standard Management ◽  
Coronary Events

Abstract Background In secondary prevention of coronary artery disease, target value of low-density lipoprotein cholesterol (LDL-C) &lt;100 mg/dL is recommended as standard management in Japanese guideline. The guideline also stated that strict management of LDL-C targeting &lt;70 mg/dL is considered in some high risk patients. However, in Japanese patients, effectiveness of more strict management of LDL-C lowering therapy for prevention of long-term cardiovascular events remains unclear. Purpose The purpose of the present study was to evaluate whether the strict management of LDL-C targeting &lt;70 mg/dL was effective to prevent recurrence of long-term coronary events than standard management in patients with previous percutaneous coronary intervention (PCI). Methods We investigated 344 patients with previous PCI who underwent late coronary angiography to examine recurrence of cardiac ischemia beyond the early phase of restenosis from January 2007 to August 2019. Patients were stratified into three groups according to achieved LDL-C value; LDL-C &lt;70mg/dL (n=53), 70 to &lt;100mg/dL (n=130) and ≥100mg/dL (n=161). Endpoints of this study were recurrence of cardiac ischemia presenting as acute coronary syndrome (recurrence-ACS) and any late coronary revascularization. Results During average 7.1 years follow-up, 200 patients (58%) underwent any late coronary revascularization. In 94 of those patients, recurrence-ACS was observed. The incidence of recurrence-ACS was significantly lower in patients with achieved LDL-C &lt;70mg/dL than in those with LDL-C 70 to &lt;100mg/dL and LDL-C ≥100mg/dL (p=0.009 and p=0.001, respectively), however, there was no difference between patients with LDL-C 70 to &lt;100mg/dL and LDL-C ≥100mg/dL (p=0.140). Any late revascularization was significantly lower in patients with achieved LDL-C &lt;70mg/dL and in those with LDL-C 70 to &lt;100mg/dL than in those with LDL-C ≥100mg/dL (p=0.002 and p&lt;0.001, respectively), however, no difference was found between patients with LDL-C &lt;70mg/dL and LDL-C 70 to &lt;100mg/dL (p=0.119). Moreover, in patients with achieved LDL-C &lt;100mg/dL (n=183), multivariate analysis identified that LDL-C (HR 1.035, p=0.007) and HbA1c (HR 1.338, p=0.001) were independent predictors of recurrence-ACS. In contrast, only using statins (HR 0.461, p=0.009) was an independent predictor of recurrence-ACS in patients with achieved LDL-C ≥100mg/dL. Conclusions LDL-C was the important residual risk of recurrence-ACS even after recommended standard LDL-C lowering management had been achieved. More strict management of LDL-C targeting to &lt;70mg/dL should be considered to prevent recurrence-ACS for wider range of Japanese patients in secondary prevention. Incidence of late coronary events Funding Acknowledgement Type of funding source: None

Abstract P560: Delipid Extracorporeal Lipoprotein Filter System: A New Lipid-Lowering Therapy for Acute Ischemic Stroke Patients

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Yuqiong Jiao ◽  
Ting Ye ◽  
Xiang Han
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasma Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Adsorption System ◽  
Stroke Patients ◽  
Safety Parameters

Objectives: The purpose of this study was to illustrate a new low-density lipoprotein cholesterol (LDL-C) adsorption system, Delipid Extracorporeal Lipoprotein filter from Plasma (DELP) system, and evaluate its safety and efficacy in acute ischemic stroke patients. Methods: This is an observational study of 22 acute ischemic stroke patients who underwent DELP treatment from March to August 2019. The DELP system was composed of a plasma filter JX-DELP, a COM.TEC cell separator and Tubing P1R Plasma Treatment Set. Clinical data and laboratory results including plasma lipids and some safety parameters before and after the apheresis were collected and analyzed. Results: The present study included 22 patients (15 males, 7 females, 59.95±13.71 years). The mean LDL-C was significantly reduced from 3.36±0.64 mmol/L to 2.30±0.53 mmol/L (31.5%, p <0.001, n=22) during a single DELP treatment, and from 3.59±0.48 mmol/L to 1.85±0.50 mmol/L (48.2%, p <0.001, n=13) after two apheresis, respectively. No clinically relevant changes were observed in hematologic safety parameters during DELP treatments. Conclusions: We concluded that the new LDL-C adsorption system is a promising method for timely and controllable LDL-C administration in acute ischemic stroke patients in view of its high efficacy, simple operation, and safety.

Lipid disorders in pregnancy

2021 ◽  
Vol 27 ◽  
Author(s):  
Anastasios Liberis ◽  
Stamatis Petousis ◽  
Panagiotis Tsikouras
Keyword(s):  
Pregnant Women ◽  
Low Density Lipoprotein ◽  
Safety Data ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Disorders ◽  
Severe Hypertriglyceridemia ◽  
History Of ◽  
Lipid Lowering Agents ◽  
In Pregnancy

: Dyslipidemia represents a major risk factor for cardiovascular disease. In addition, severe hypertriglyceridemia is an important cause of acute pancreatitis. Accordingly, the increase in serum lipid levels that are observed during pregnancy have potentially important implications. The management of dyslipidemia in pregnancy is further complicated by the lack of safety data during this period for most of the lipid-lowering agents. In the present review, we discuss the most important lipid disorders in pregnant women and their management. Pregnancy is characterized by increases in both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, which might result in severe complications both for the mother and the fetus. Accordingly, LDL-C and triglyceride levels should be monitored during pregnancy, particularly in women with a history of dyslipidemia. Diet is the mainstay of management of dyslipidemia in pregnant women and apheresis can also be considered in patients with homozygous familial hypercholesterolemia or severe hypertriglyceridemia. However, there is a pressing need for studies that with evaluate the safety of lipid-lowering agents during pregnancy.

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.

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.

scholarly journals Familial Defective Apolipoprotein B-100: A Study of Patients from Lipid Clinics in Scotland and Wales

1996 ◽  
Vol 33 (5) ◽  
pp. 443-450 ◽  
Author(s):  
Philip R Wenham ◽  
Peter Bloomfield ◽  
Gillian Blundell ◽  
Michael D Penney ◽  
Peter W H Rae ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Common Ancestor ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pedigree Analysis ◽  
Lipid Lowering ◽  
Low Density Lipoprotein Cholesterol ◽  
Apo B ◽  
History Of

Familial defective apolipoprotein (apo) B-100 (FDB) is an autosomal codominant disorder, which may be associated with hypercholesterolaemia. The defect is caused by the substitution of glutamine for arginine at amino acid residue 3500 of apo B-100. A total of 357 hypercholesterolaemic patients, 48 with a clinical diagnosis of familial hypercholesterolaemia attending lipid clinics in Scotland and Wales, were screened for the presence of FDB. Seven unrelated individuals, five of whom had a family history of coronary heart disease, and a further 11 first-degree relatives, were shown to be heterozygous for the mutation. Pedigree analysis demonstrated the mutation to be present on a single haplotype, suggesting that in Britain it is inherited from a common ancestor. Treatment of 11 heterozygous individuals with lipid-lowering medication showed falls in total and low density lipoprotein cholesterol ranging from 11·6 to 38·8% and 5·3 to 49·5%, respectively. In view of the condition's association with coronary heart disease and hypercholesterolaemia, it may be worthwhile identifying carriers attending lipid clinics, so that affected siblings can be offered cholesterol-lowering treatment where necessary.

scholarly journals Effect of coexisting vascular disease on long-term risk of recurrent events after TIA or stroke

Neurology ◽  
2019 ◽  
Vol 93 (7) ◽  
pp. e695-e707 ◽  
Author(s):  
Marion Boulanger ◽  
Linxin Li ◽  
Shane Lyons ◽  
Nicola G. Lovett ◽  
Magdalena M. Kubiak ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Ischemic Stroke ◽  
High Risk ◽  
Secondary Prevention ◽  
Recurrent Events ◽  
Lipid Lowering ◽  
Prevention Guidelines ◽  
Coronary Events ◽  
Ischemic Events ◽  
Age And Sex

ObjectiveTo determine whether patients with TIA or ischemic stroke with coexisting cardiovascular disease (i.e., history of coronary or peripheral artery disease) are still at high risk of recurrent ischemic events despite current secondary prevention guidelines.MethodsIn a population-based study in Oxfordshire, UK (Oxford Vascular Study), we studied consecutive patients with TIA or ischemic stroke for 2002–2014. Patients were treated according to current secondary prevention guidelines and we determined risks of coronary events, recurrent ischemic stroke, and major bleeding stratified by the presence of coexisting cardiovascular disease.ResultsAmong 2,555 patients (9,148 patient-years of follow-up), those (n = 640; 25.0%) with coexisting cardiovascular disease (449 coronary only; 103 peripheral only; 88 both) were at higher 10-year risk of coronary events than those without (22.8%, 95% confidence interval 17.4–27.9; vs 7.1%, 5.3–8.8; p < 0.001; age- and sex-adjusted hazard ratio [HR] 3.07, 2.24–4.21) and of recurrent ischemic stroke (31.5%, 25.1–37.4; vs 23.4%, 20.5–26.2; p = 0.0049; age- and sex-adjusted HR 1.23, 0.99–1.53), despite similar rates of use of antithrombotic and lipid-lowering medication. However, in patients with noncardioembolic TIA/stroke, risk of extracranial bleeds was also higher in those with coexisting cardiovascular disease, particularly in patients aged <75 years (8.1%, 2.8–13.0; vs 3.4%, 1.6–5.3; p = 0.0050; age- and sex-adjusted HR 2.71, 1.16–6.30), although risk of intracerebral hemorrhage was not increased (age- and sex-adjusted HR 0.36, 0.04–2.99).ConclusionsAs in older studies, patients with TIA/stroke with coexisting cardiovascular disease remain at high risk of recurrent ischemic events despite current management. More intensive lipid-lowering might therefore be justified, but benefit from increased antithrombotic treatment might be offset by the higher risk of extracranial bleeding.

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