scholarly journals EXPERIENCE WITH THE USE OF EVOLOCUMAB THERAPY IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA (IN KARELIA REPUBLIC)

2020 ◽  
pp. 42-47
Author(s):  
V. A. Korneva ◽  
T. Yu. Kuznetsova ◽  
N. N. Natal’ya N. Vezikova
Keyword(s):  
Side Effects ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Statistical Processing ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Risk Patients ◽  
History Of ◽  
Lipid Spectrum

Aim: to evaluate the efficacy and safety of the use of evolocumab in patients with familial hypercholesterolemia (FH).Materials and methods: Fifteen patients with a definite FH were treated with PCSK9 inhibitors, in 11 patients with a history of CAD. Eight patients (53.3%) received evolocumab (Repata) subcutaneously 140 mg once every 2 weeks, their average age was 51.4±2.3 years, 6 men. Lipid spectrum, ALT, AST, creatinine, glucose, Lp (a) were evaluated after 3, 6, 12 and 18 months, the ECG and the clinical picture were monitored. Evolocumab was prescribed in connection with the failure to achieve the target LDL. Before the start of therapy, 7 patients received statins, 5 statins with ezetemib, 1 patient did not receive lipid-lowering therapy due to intolerance. The target LDL levels were considered: for very high risk patients less than 1.4 mmol/L, high risk – less than 1.8 mmol/L. Statistical processing of the material was performed using STATISTICA10.0.Results: On the background of evolocumab therapy, the average level of LDL after 3 months of therapy decreased by 56.4% (from 3.9±0.3 to 1.71±0.2 mmol/L), the effect persisted after a year. All patients did not stop the therapy; there were no side effects, including local ones. Target LDL was achieved in 62.5% of patients, the average LDL level after 3 months of therapy decreased by 56.4% in patients from the initial, including the case of monotherapy with evolocumab. The Lp (a) level during therapy decreased by 30%.Conclusions: Evolocumab allows to increase the achievement of the target LDL level on 40% in FH patients; target LDL level was achieved in 62.5%. LDL decreased after 3 months by 56.4%, remaining stable with prolonged therapy. The decrease in Lp(a) reached 30%. Evolocumab therapy was characterized by high adherence and the absence of side effects.

P938Extensive formation of atherosclerotic cardiovascular disease in subjects with severe familial hypercholesterolemia defined by the international atherosclerosis society criteria

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Funabashi ◽  
Y Kataoka ◽  
M Harada-Shiba ◽  
M Hori ◽  
T Doi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Peripheral Artery Disease ◽  
Cardiac Death ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Lowering Therapy ◽  
Artery Disease

Abstract Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia (FH)” as a FH phenotype with the highest cardiovascular risk. Coronary artery disease (CAD) represents a major atherosclerotic change in FH patients. Given their higher LDL-C level and atherogenic clinical features, more extensive formation of atherosclerosis cardiovascular disease including not only CAD but stroke/peripheral artery disease (PAD) may more frequently occur in severe FH. Methods 481 clinically-diagnosed heterozygous FH subjects were analyzed. Severe FH was defined as untreated LDL-C>10.3 mmol/l, LDL-C>8.0 mmol/l+ 1 high-risk feature, LDL-C>4.9 mmol/l + 2 high-risk features or presence of clinical ASCVD according to IAS proposed statement. Cardiac (cardiac death and ACS) and non-cardiac (stroke and peripheral artery disease) events were compared in severe and non-severe FH subjects. Results Severe FH was identified in 50.1% of study subjects. They exhibit increased levels of LDL-C and Lipoprotein (a) with a higher frequency of LDLR mutation. Furthermore, a proportion of %LDL-C reduction>50% was greater in severe FH under more lipid-lowering therapy (Table). However, during the observational period (median=6.3 years), severe FH was associated with a 5.9-fold (95% CI, 2.05–25.2; p=0.004) and 5.8-fold (95% CI, 2.02–24.7; p=0.004) greater likelihood of experiencing cardiac-death/ACS and stroke/PAD, respectively (picture). Multivariate analysis demonstrated severe FH as an independent predictor of both cardiac-death/ACS (hazard ratio=3.39, 95% CI=1.12–14.7, p=0.02) and stroke/PAD (hazard ratio=3.38, 95% CI=1.16–14.3, p=0.02) events. Clinical characteristics of severe FH Non-severe FH Severe FH P-value Baseline LDL-C (mmol/l) 5.3±1.5 6.6±2.0 <0.0001 Lp(a) (mg/dl) 15 [8–28] 21 [10–49] <0.0001 LDLR mutation (%) 49.6% 58.9% 0.00398 On-treatment LDL-C (mmol) 133 [106–165] 135 [103–169] 0.9856 %LDL-C reduction>50% 21.3% 49.8% <0.0001 High-intensity statin (%) 13.3% 42.3% <0.0001 PCSK9 inhibitor (%) 6.3% 21.2% <0.0001 Clinical outcome Conclusions Severe FH subjects exhibit substantial atherosclerotic risks for coronary, carotid and peripheral arteries despite lipid lowering therapy. Our finding underscore the screening of systemic arteries and the adoption of further stringent lipid management in severe FH patients.

scholarly journals 2214Prevalence and severity of coronary disease in patients with familial hypercholesterolemia hospitalized for an acute myocardial infarction: data from the RICO survey

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Farnier ◽  
B Mouhat ◽  
T Pommier ◽  
H Yao ◽  
M Maza ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Familial Hypercholesterolemia ◽  
Statin Treatment ◽  
University Hospital ◽  
Lipid Lowering ◽  
Syntax Score ◽  
World Population ◽  
Lipid Lowering Therapy ◽  
History Of ◽  
Acute Mi

Abstract Aim Individuals with heterozygous familial hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI). However, coronary artery disease (CAD) burden of FH remains not well described. From a large database of a regional registry of acute MI, we aimed to address prevalence of FH and severity of CAD. Methods Consecutive patients hospitalized with MI in a multicentre database from 2001–2017 were considered. An algorithm, adapted from Dutch Lipid Clinic Network criteria, was built upon 4 variables (LDL-cholesterol (LDL-C) and lipid lowering agents, premature and family history of CAD) to identify FH probabilities. Results Among the 11624 patients included in the survey, 249 (2.1%) had probable/definite FH (score ≥6), and 2405 (20.7%) had possible FH (score 3–5). When compared with patients without FH (score 0–2), FH patients (score ≥6) were 20y younger (51 (46–57) vs 71 (61–80) y, p<0.001), with a lower rate of hypertension (47 vs 59%, p<0.001), diabetes (17 vs 25%, p<0.001) and prior stroke (4 vs 8%, p=0.016), but a higher prevalence of smokers (56 vs 23%, p<0.001), personal (20 vs 15%, p=0.02) or familial history of CAD (78 vs 18%, p<0.001). Chronic statin treatment was only used in 48% of FH patients and ezetimibe in 8%. After adjustment for age, sex and diabetes, FH patients were characterized by increased extent of CAD (syntax score 11 (4–19) vs 7 (1–13), p<0.001) and multivessel disease (55 vs 40%, p<0.001). Conclusion In this large real world population of acute MI, a high prevalence of FH was found. FH patients were characterized by their young age associated with the severity of CAD burden and limited use of preventive lipid lowering therapy. Acknowledgement/Funding University Hospital Center Dijon Bourgogne, Agence Régionale de Santé Bourgogne Franche Comté, France

Becoming more focused therapeutic lipid patterns: results from the Hungarian MULTI GAP 2010

2011 ◽  
Vol 152 (21) ◽  
pp. 822-827 ◽  
Author(s):  
István Reiber ◽  
György Paragh ◽  
László Márk ◽  
Gyula Pados
Keyword(s):  
High Risk ◽  
Goal Attainment ◽  
Treatment Strategies ◽  
Hdl Cholesterol ◽  
High Risk Group ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Frequent Use ◽  
Risk Patients

Previous studies have found that many high-risk patients are not achieving their LDL-cholesterol goals, and many patients, despite being treated with lipid-lowering therapy, also have elevated triglycerides and/or low levels of HDL-cholesterol. Aims: Authors analyzed the treatment strategies for dyslipidemic subjects following cardiovascular events similarly to their former survey from 2008 and 2009. Methods: In the MULTI GAP (MULTI Goal Attainment Problem) 2010 trial data from standard and structured questionnaires of 2332 patients were processed. Authors analyzed the proportion of the patients reaching target levels for total cholesterol, LDL-C, HDL-C, A-C (atherogen cholesterol) and triglyceride. Results: 15% (n = 355) of the patients did not receive any lipid lowering treatment. 44% of the patients treated by specialists reached the target LDL-C level of 2.5 mmol/l. In „high risk” group target levels for HDL-C were reached by 61% of the patients, and for triglyceride by 43% of the subjects. 43% of the patients with the best compliance (>90%) reached the target LDL-C level of 2.5 mmol/l. Conclusion: There is a need for more effective lipid lowering therapy with more frequent use of higher doses of statins or combinations of lipid lowering drugs. Orv. Hetil., 2011, 152, 822–827.

Cross-Sectional Study to Estimate the Prevalence of Familial Hypercholesterolemia in Selected Regions of the Russian Federation: Relevance, Design of the Study and Initial Characteristics of the Participants

2020 ◽  
Vol 16 (1) ◽  
pp. 24-32
Author(s):  
A. N. Meshkov ◽  
A. I. Ershova ◽  
S. A. Shalnova ◽  
A. S. Alieva ◽  
S. S. Bazhan ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Cardiovascular Diseases ◽  
Familial Hypercholesterolemia ◽  
Russian Federation ◽  
Regional Differences ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
History Of ◽  
The Russian Federation

Aim. To study the prevalence of familial hypercholesterolemia (FH), the characteristics of the clinical features and treatment of the disease in selected regions of the Russian Federation, this article describes the design and initial characteristics of patients included in the study.Material and methods. The study participants were selected among those included in the study “Epidemiology of cardiovascular risk factors and diseases in the regions of the Russian Federation” (ESSE-RF) in different regions of the Russian Federation. The study included individuals with lowdensity lipoprotein cholesterol (LDL-C) levels >4.9 mmol/l or LDL-C levels >1.8 mmol/l, but ≤4.9 mmol/l during statin therapy, according to the data obtained in the ESSE-RF study. These persons are invited for examination and questioning by experts in the field of FH diagnostics. On the basis of the survey data and provided medical documentation, the following information is collected: age, sex, smoking status, presence of hypertension, history of coronary artery disease, stroke, atherosclerosis of cerebral and peripheral arteries, LDL-C level, type, volume and duration of lipid-lowering therapy throughout life, presence and dates of secondary causes of hyperlipidemia, information about the family history of development of early cardiovascular diseases and atherosclerotic diseases, increased levels of LDL-C in relatives of the 1st and 2nd degree of kinship. All patients are examined for the presence of tendon xanthomas (Achilles, metacarpal, elbow, knee tendons) and Corneal arcus. During the visit, blood is taken for subsequent biobanking, measurement of current blood lipid levels, elimination of secondary forms of hypercholesterolemia (for subsequent determination of liver enzymes, thyroid stimulating hormone) and genetic testing. The diagnosis of FH is based on Dutch Lipid Clinical Network Criteria (DLCN). Besides, all participants in the study are tested for compliance with the diagnosis of FH according to Simon Broome criteria. All patients with a definite or probable diagnosis of FH according to DLCN or Simon Broome criteria are subjected to ultrasound examination of carotid, femoral arteries and heart and molecular genetic testing for LDLR, APOB and PCSK9 gene variants.Results. Out of 16 360 participants of the ESSE-RF study in 10 regions, 1787 people (10,9%) met the criteria for inclusion in this study. Among them, men accounted for 35.4%, of which 1150 (7%) patients had a LDL-C level >4.9 mmol/l and 637 (3,9%) had a LDL-C level from 1,81 mmol/l to 4.9 mmol/l during lipid-lowering therapy. When compared to the original cohorts of participants from the 10 regions as compared to 3 previously surveyed regions and selected sub-groups within these cohorts we observed significant differences in several parameters such as age, total cholesterol level, triglycerides, LDL-C, the frequency of cardiovascular diseases, that may indicate regional differences in FH prevalence.Conclusion. The analysis of clinical data of the participants of the ESSE-RF study shows that more than 10% of individuals require an additional examination to verify the FH diagnosis, and regional differences in the FH prevalence are possible.

Effective Lipid-lowering Therapy in High-risk Patients

2011 ◽  
Vol 1 (111) ◽  
Author(s):  
John J.P. Kastelein ◽  
Benoit J Arsenault ◽  
Jean-Claude Tardif
Keyword(s):  
High Risk ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
High Risk Patients ◽  
Lowering Therapy ◽  
Risk Patients

scholarly journals Exposure to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the association with neurocognitive side effects: a meta-analysis and meta-regression

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Hirsh-Raccah ◽  
A Yanovsky ◽  
V Rotshild ◽  
H Danenberg ◽  
R Eliaz ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Meta Analysis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Lowering Therapy ◽  
Meta Regression ◽  
Meta Analyses

Abstract Background Lipid lowering therapy may be associated with impaired cognitive function. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse effects remains unclear. Purpose To assess the neurocognitive safety of PCSK9 inhibitors using meta-analysis and meta-regression of randomized controlled trials (RCTs). Methods PubMed (MEDLINE), Embase and Cochrane library were searched. RCTs that reported assessments of neurocognitive outcomes of participants using PCSK9 inhibitors, with a duration of follow up of at least six months were included. The results of the search were screened by two independent reviewers. Any disagreements were resolved by consensus. The research was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for meta-analyses. Results were pooled using random-effects models. The primary safety outcome of this analysis was defined as the reported incidence of neurocognitive adverse effects. Results Results of 21 trials were included in the analysis. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. No significant difference in the incidence of neurocognitive side effects between the treatment and control groups was identified (RR=1.01, 95% CI: 0.86–1.19, I2=3%). Same results were seen in separate analysis for each of the medicines (Alirocumab- RR=0.88, 95% CI: 0.72–1.08, I2=0%, Evolocumab- RR=1.42, 95% CI: 0.74–2.73, I2=55%). In a meta-regression analysis there was no statistically significant association between the assessed and the risk for neurocognitive side effects. Conclusions Pooled results of our meta-analysis and meta-regression clearly show that the exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse events. Due to the increasing proportion of patients using lipid-lowering therapy these results are positively reassuring. However, more data from long-term outcomes studies is needed to further evaluate the effect of longer exposure to PCSK9 inhibitors Funding Acknowledgement Type of funding source: None

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