scholarly journals Improvement of retinal microvascular function after initiation of lipid-lowering therapy with PCSK9 inhibitors – an observational study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Naegele ◽  
Y Raemy ◽  
J Barthelmes ◽  
L Kreysing ◽  
T Haider ◽  
...  
Keyword(s):  
High Risk ◽  
Arterial Stiffness ◽  
Observational Study ◽  
Augmentation Index ◽  
Microvascular Function ◽  
Inhibitor Therapy ◽  
Lipid Lowering ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Risk Patients

Abstract Background Hypercholesterolemia is associated with endothelial dysfunction. While good evidence exists for the beneficial endothelial effects of first-line lipid-lowering drugs (statins), less is known on the new class of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. This is particularly true for the differential effects on micro- and macrovascular endothelial function and arterial stiffness. Purpose The goal of this study was to study the change in retinal microvascular dysfunction, brachial artery endothelial function and arterial stiffness in high-risk cardiovascular risk patients before and after initiation of PCSK9 inhibitor therapy with alirocumab or evolocumab. Methods In this prospective observational study, cardiovascular high-risk patients with a clinical indication for PCSK9 inhibitors were included for the measurement of retinal microvascular function (flicker light-induced dilatation of retinal arterioles and venules, FIDart and FIDven respectively; retinal arteriovenous ratio, AVR), brachial artery flow-mediated dilatation (FMD) and arterial stiffness (pulse wave velocity, PWV; augmentation index, AI). Measurements were performed at baseline, after 3 months and after 12 months of PCSK9 inhibitor therapy. The primary endpoint was the change in FIDart after 12 months of therapy compared to baseline. Results We recruited 48 patients (mean age 57±11 years, 27% female, 81% coronary artery disease) which began treatment with alirocumab or evolocumab in our lipid outpatient clinic. 6 patients were excluded from the analysis (n=3 stopped due to side effects, n=1 stopped due to new metastatic cancer, n=1 moved abroad, n=1 no retinal vessel analysis possible). LDL cholesterol was reduced from 3.8±1.2 to 1.5±0.8 and 1.8±0.9 mmol/L at 3 and 12 months respectively (all p<0.001). There was no significant change in systolic blood pressure during therapy. The primary endpoint FIDart was significantly increased after 12 months of PCSK9 inhibitor therapy compared to baseline (3.4±2.3 vs. 2.6±1.6%, p=0.01). Among the secondary endpoints, augmentation index improved at 12 months vs. baseline (21±12 vs. 24±9%, p=0.03). No significant change was seen for FIDven, AVR, FMD and PWV after 3 and 12 months of therapy. Conclusion In cardiovascular high-risk patients, PCSK9 inhibition is associated with an improvement of retinal microvascular function and augmentation index after one year of therapy. No effects were seen for macrovascular parameters such as FMD or PWV in our cohort. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): University Hospital Zurich, AGLA Grant (sponsored by Amgen)

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.

The new LDL-C target <55 mg/dL is achieved by less than 40% of very high risk patients with familial hypercholesterolaemia despite receiving PCSK9 inhibitors: real world data

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Rallidis ◽  
C Vlachopoulos ◽  
E Liberopoulos ◽  
I Skoumas ◽  
E Kiouri ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Familial Hypercholesterolaemia ◽  
Lipid Lowering ◽  
Additional Risk Factor ◽  
Pcsk9 Inhibitors ◽  
High Risk Patients ◽  
Lipid Clinic ◽  
Risk Patients ◽  
Very High

Abstract Background The recently published ESC/EAS guidelines for the management of dyslipidaemias have lowered the low-density lipoprotein cholesterol (LDL-C) target in the very high risk patients below 55 mg/dL. Purpose To examine how achievable is this target in very high risk patients receiving a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) on top of lipid-lowering treatment (LLT). Methods The cohort comprised 158 patients who attended the lipid clinic of 3 hospitals in Greece and started treatment with PCSK9i. Patients were requested to attend the lipid clinic 3 months after the initiation of PCSK9i. Results Ninety percent of patients had heterozygous familial hypercholesterolaemia (heFH) and 75% had cardiovascular disease (CVD). One hundred forty patients were classified as very high risk because they had either cardiovascular disease (CVD) or heFH with an additional risk factor for whom a target &lt;55 mg/dL is currently recommended. Of those very high risk patients, 105 (75%) were given PCSK9i due to failure to achieve LDL-C targets despite maximum LLT (high intensity statin at maximum tolerated dose + ezetimibe) while in the rest of cases the indication was statin intolerance. The mean reduction of LDL-C at 3 months was 56.2%. Among 105 very high risk patients (all had heFH), LDL-C below 55 mg/dL was achieved by 37.1% while the previously LDL-C target &lt;70 mg/dL was achieved by 60% (Figure 1). Conclusions The new LDL-C target &lt;55 mg/dL is achieved by &lt;40% of very high risk patients with heFH despite receiving triple LLT, i.e. PCSK9i + statin + ezetimibe. This therapeutic gap suggests that there is still need for more effective LLT in very high risk heFH patients to maximize their clinical benefit. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review

2021 ◽  
Vol 12 ◽  
pp. 204209862095927
Author(s):  
Wei C. Yuet ◽  
Didi Ebert ◽  
Michael Jann
Keyword(s):  
Cognitive Impairment ◽  
Adverse Events ◽  
The United States ◽  
Narrative Review ◽  
Lipid Lowering ◽  
Patient Specific ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Receptor Modulation

Neurocognitive adverse events have been observed with the widespread use of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or “statins,” which reduce low-density lipoprotein cholesterol (LDL-C) levels and subsequently cardiovascular risk. The United States Food and Drug Association directed manufacturers of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors to monitor for neurocognitive adverse events due to their potent effects on LDL-C reduction, which is a proposed mechanism for neuronal cell dysfunction. Other proposed mechanisms for PCSK9 inhibitor-associated neurocognitive adverse events include N-methyl-d-aspartate receptor modulation, dysregulation of lipid and glucose metabolism, and patient-specific risk factors for cognitive impairment. The purpose of this narrative review article is to describe the proposed mechanisms, incidence of neurocognitive adverse events from phase II and III trials for PCSK9 inhibitors, neurocognitive assessments utilized in clinical trials, and clinical implications. Given the increasing prevalence of PCSK9 inhibitor use and the neurocognitive adverse events observed with prior lipid-lowering therapies, clinicians should be aware of the risks associated with PCSK9 inhibitors, especially when therapy is indicated for patients at high risk for cardiovascular events. Overall, the incidence of PCSK9 inhibitor-associated neurocognitive appears to be uncommon. However, additional prospective studies evaluating cognitive impairment may be beneficial to determine the long-term safety of these agents.

scholarly journals Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Laurenz T. Fischer ◽  
Daniel A. Hochfellner ◽  
Lisa Knoll ◽  
Tina Pöttler ◽  
Julia K. Mader ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Real World ◽  
Cardiovascular Events ◽  
Care Center ◽  
Tertiary Care ◽  
Lipid Lowering ◽  
Tertiary Care Center ◽  
Pcsk9 Inhibitors ◽  
Real World Data ◽  
Pcsk9 Inhibitor

Abstract Background The lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of individuals with high cardiovascular risk. As real-world data are still scarce, specifically in patients with type 2 diabetes (T2D), the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care. Methods A retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (alirocumab or evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels as well as subsequent cardiovascular events were assessed over an observation period of 18 months. Results We identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. 26.2% of the population had a concomitant diabetes diagnosis. Intolerance to statins (83.1%), ezetimibe (44.7%) or both agents (42.6%) was reported frequently. Three months after initiation of PCSK9 inhibitor therapy, 61.2% of the patients achieved LDL-C levels < 70 mg/dl, and 44.1% LDL-C levels < 55 mg/dl. The median LDL-C was lowered from 141 mg/dl at baseline, to 60 mg/dl after 3 months and 66 mg/dl after 12 months indicating a reduction of LDL-C as follows: 57.5% after 3 months and 53.6% after 12 months. After 3 months of observation, target achievement of LDL-C was higher in patients with T2D compared to non-diabetes patients; < 55 mg/dl: 51% vs. 41.5%; < 70 mg/dl 69.4 vs. 58.5%. After 12 months even more pronounced target LDL achievement in T2D was demonstrated < 55 mg/dl: 58.8% vs. 30.1%; < 70 mg/dl 70.6 vs. 49.6%. Patients with insufficiently controlled T2D (HbA1c > 54 mmol/mol) had a higher reduction in LDL-C but still were more likely to subsequent cardiovascular events. Conclusions Significant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. The percentage of patients with T2D meeting recommended LDL-C targets was higher than in those without T2D. Still some patients did not achieve LDL-C levels as recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.

scholarly journals Lipoprotein Particle Predictors of Arterial Stiffness after 17 Years of Follow Up: The Malmö Diet and Cancer Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jacob Hartz ◽  
Ronald M. Krauss ◽  
Mikael Göttsater ◽  
Olle Melander ◽  
Peter Nilsson ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
High Risk ◽  
Arterial Stiffness ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Cancer Study ◽  
Lipoprotein Particle ◽  
Ldl Particles ◽  
Diet And Cancer

Background. Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malmö Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years. Methods. Lipoprotein particle analysis was performed on 2,505 men and women from Malmö, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement. Results. The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG. Conclusions. The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.

scholarly journals Dyslipidaemias and Cardiovascular Disease: Focus on the Role of PCSK9 Inhibitors

2020 ◽  
Vol 27 (27) ◽  
pp. 4494-4521 ◽  
Author(s):  
Olga Panagiotopoulou ◽  
Scott T. Chiesa ◽  
Dimitrios Tousoulis ◽  
Marietta Charakida
Keyword(s):  
Phase Iii ◽  
Short Term ◽  
Pcsk9 Inhibitors ◽  
Cardiovascular Risk Reduction ◽  
Pcsk9 Inhibitor ◽  
Phase Iii Clinical Trials ◽  
Risk Patients ◽  
Event Rates ◽  
Disease Focus

Genetic, experimental and clinical studies have consistently confirmed that inhibition of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) can result in significant lowering of LDL-C and two fully human PCSK9 monoclonal antibodies have received regulatory approval for use in highrisk patients. Co-administration of PCSK9 with statins has resulted in extremely low LDL-C levels with excellent short-term safety profiles. While results from Phase III clinical trials provided significant evidence about the role of PCSK9 inhibitors in reducing cardiovascular event rates, their impact on mortality remains less clear. PCSK9 inhibitor therapy can be considered for high-risk patients who are likely to experience significant cardiovascular risk reduction.

Abstract P275: Demographic and Clinical Profile of Patients with Risk Factors for Coronary Heart Disease (CHD) Defined by National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III Guidelines

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
David M Kern ◽  
Sanjeev Balu ◽  
Ozgur Tunceli ◽  
Swetha Raparla ◽  
Deborah Anzalone
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Groups ◽  
Lipid Lowering ◽  
High Risk Patients ◽  
Low Hdl ◽  
Risk Patients ◽  
Artery Disease ◽  
Very High ◽  
Statin Use

Introduction: This study aimed to compare the demographic and clinical characteristics of patients with different risk factors for CHD as defined by NCEP ATP III guidelines. Methods: Dyslipidemia patients (≥1 medical claim for dyslipidemia, ≥1 pharmacy claim for a statin, or ≥1 LDL-C value ≥100 mg/dL [index date]) aged ≥18 y were identified from the HealthCore Integrated Research Environment from 1/1/2007-7/31/2012. Patients were classified as low risk (0 or 1 risk factor): hypertension, age ≥45 y [men] or ≥55 y [women], or low HDL-C), moderate/moderately high risk (≥2 risk factors), high risk (having CHD or CHD risk equivalent), or very high risk (having ACS or other established cardiovascular disease plus diabetes or metabolic syndrome). Demographics, comorbidities, medication use and lipid levels during the 12 months prior, and statin use during the 6 months post-index date were compared across risk groups (very high vs each other risk group). Results: There were 1,524,351 low-risk (mean age: 47 y; 45% men), 242,357 moderate-risk (mean age: 58 y; 59% men), 188,222 high-risk (mean age: 57 y; 52% men), and 57,469 very-high-risk (mean age: 63 y; 61% men) patients identified. Mean Deyo-Charlson comorbidity score differed greatly across risk strata: 0.20, 0.33, 1.26, and 2.22 from low to very high risk (p<.0001 for each). Compared with high-risk patients, very-high-risk patients had a higher rate of ischemic stroke: 5.4% vs 4.1%; peripheral artery disease: 17.1% vs 11.6%; coronary artery disease: 8.5% vs 8.2%; and abdominal aortic aneurysm: 2.3% vs 2.0% (p<.05 for each). Less than 1% of the total population had a prior prescription for each non-statin lipid-lowering medication (bile acid sequestrants, fibrates, ezetimibe, niacin, and omega-3). Very-high-risk patients had lower total cholesterol (very-high-risk mean: 194 mg/dL vs 207, 205, and 198 mg/dL for low-, moderate-/moderately-high-, and high-risk patients, respectively) and LDL-C (very-high-risk mean: 110 mg/dL vs 126, 126, and 116 mg/dL for the other risk groups; p<.0001 for each); higher triglycerides (TG) (very-high-risk mean: 206 mg/dL vs 123, 177, and 167 mg/dL for the other groups; p<.0001 for each); and lower HDL-C (very-high-risk mean: 45 mg/dL vs 57 [p<.0001], 45 [p=.006], and 51 mg/dL [p<.0001]). Statin use was low overall (15%), but higher in the very-high-risk group (45%) vs the high- (29%), moderate-/moderately-high- (18%), and low- (12%) risk groups (p<.0001 for each). Conclusions: Despite a large proportion of patients having high lipid levels, statin use after a dyslipidemia diagnosis was low: ≥80% of all patients (and more than half at very high risk) failed to receive a statin, indicating a potentially large population of patients who could benefit from statin treatment. Prior use of non-statin lipid-lowering medications was also low considering the high TG and low HDL-C levels among high-risk patients.

Lipid Lowering Treatment Patterns and Risk of Subsequent Cardiovascular Outcomes Among Patients Initially Rejected for pcsk9 Inhibitor Therapy

2020 ◽  
Vol 14 (4) ◽  
pp. 599-600
Author(s):  
Nihar Desai ◽  
Pallavi Rane ◽  
Sasikiran Nunna ◽  
Chi-Chang Chen ◽  
Jason Exter ◽  
...  
Keyword(s):  
Treatment Patterns ◽  
Cardiovascular Outcomes ◽  
Inhibitor Therapy ◽  
Lipid Lowering ◽  
Pcsk9 Inhibitor
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