Non-familial Hypercholesterolemia Research Articles

Inclisiran (Leqvio)

CADTH recommends that Leqvio not be reimbursed by public drug plans as an adjunct to lifestyle changes, including diet, to further reduce low-density lipoprotein cholesterol (LDL-C) levels in adults who are on a maximally tolerated dose (MTD) of a statin, with or without other LDL-C–lowering therapies, and who have nonfamilial hypercholesterolemia (nFH) with atherosclerotic cardiovascular disease (ASCVD). Evidence from 2 clinical trials showed that treatment with Leqvio lowered bad cholesterol (LDL-C) in adults with nFH with ASCVD who were already being treated with the highest possible dose of statins and in those who cannot tolerate treatment with statins. A post hoc pooled analysis of major adverse cardiovascular events (MACEs) from the ORION-10 and ORION-11 trials precluded the Canadian Drug Expert Committee (CDEC) from determining whether inclisiran reduces the risk of cardiovascular morbidity and death in adults with nFH with ASCVD. Patients identified a need for treatments that are less burdensome, can reduce bad cholesterol (LDL-C) and cardiovascular morbidity and death, and improve health-related quality of life (HRQoL); however, there was not enough evidence to show that Leqvio would reduce cardiovascular morbidity and death or improve HRQoL.

First Report of Inclisiran Utilization for Hypercholesterolemia Treatment in Real-world Clinical Settings in a Middle East Population

Inclisiran is the first small interfering RNA-based treatment approved for reducing pro-atherogenic lipoproteins in patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of low-density lipoprotein cholesterol (LDL-C). We report the first evaluation of the effects of inclisiran in a Middle East population. We conducted a retrospective review of patients initiating inclisiran treatment at an outpatient diabetology, endocrinology, and cardiology center between May 2021 and December 2022. All patients followed up for 90 days or more, or with at least 1 lipid determination post initiation were included. Participants were categorized into primary prevention (n = 57) and secondary prevention (n = 89) groups according to previous atherosclerotic cardiovascular disease. Inclisiran was initiated in 146 patients; mean (SD) age was 54.8 (12.12) years, 82 patients (56.2%) were male, 28 patients (19.2%) had received a diagnosis of familial hypercholesterolemia, 89 patients (61%) had received a diagnosis of diabetes mellitus, and 35 patients (23.9%) had a statin intolerance. Median (interquartile range) follow-up was 137 (90 to 193) days. At 90 days, median (interquartile range) reductions in serum LDL-C and triglycerides were -37.9% (-9.5% to -51.2%) and -12.0% (-9.8% to -40.5%), respectively, in primary prevention and -54.1% (-17.1% to -71.4%) and -15.3% (-14% to -38.8%), respectively, in secondary prevention (all, P < 0.001). LDL-C goals were attained in 110 patients (75.3%). Nonattainment of LDL-C goal was attributed to system effect in 26 patients (72.2%), biological effect in 5 patients (13.9%), and discontinuation of treatment in 5 patients (13.9%). Therapy was well tolerated. This study is the first from the Middle East and North Africa region that reported the real-world efficacy and safety profile of inclisiran in a mixed-risk population of patients with heterozygous familial hypercholesterolemia and other non-familial hypercholesterolemia indications. Clinically meaningful and sustained reductions in pro-atherogenic lipids with good tolerability were observed after inclisiran initiation. Fewer AEs were reported in this predominantly Arabic population, consistent with previous safety reports for inclisiran. It is important to note that no patient stopped inclisiran treatment due to AEs. Strengths of our study included an optimal cohort, patient heterogeneity, and high retention. In addition, we were able to report mean robust effects of inclisiran and good medication tolerability, quite like randomized studies and open-label extension periods. Despite this, our study had some limitations, including selection bias due to the retrospective design and the absence of a comparative group.

Effect of Combination Therapy with Ezetimibe and Statins versus Statin Monotherapy on Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: Lipid-lowering agents such as ezetimibe are recommended in uncontrolled hyperlipidemia for primary and secondary prevention of cardiovascular disease. Carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis and a predictor of cardiovascular and cerebral events. The effects of ezetimibe on CIMT have been inconsistently reported. The aim of this meta-analysis is to compare the effects of ezetimibe/statin and statin alone therapies on CIMT reduction. Materials and Methods: The PubMed, Embase, and Cochrane library databases were searched for randomized controlled trials (RCTs) published prior to 26 January 2023 with the MeSH keywords 'Ezetimibe' and 'Carotid Intima-Media Thickness'. The results were presented as standard mean difference (SMD) with 95% confidence intervals using the random-effect model method, and heterogeneity was assessed. Subgroup, meta-regression, and sensitivity analyses were conducted. Results: Five RCTs with 642 participants were included. CIMT reduction was not significantly different between the ezetimibe/statin and statin alone groups. However, in subgroup analyses, CIMT in the ezetimibe/statin group was significantly reduced in patients with non-familial hypercholesterolemia (SMD: -0.34 mm and p = 0.002) and in patients with secondary prevention (SMD: -0.38 mm and p = 0.002). The low-density lipoprotein cholesterol level was significantly reduced in the ezetimibe/statin group (SMD: -0.58 mg/dL and p < 0.001). Conclusions: The effect of ezetimibe on CIMT reduction was shown in non-familial hypercholesterolemia and secondary prevention. These results suggest that the efficacy of ezetimibe may vary with potential CIMT reduction benefits in certain subpopulations.

Tafolecimab: First Approval.

Tafolecimab (SINTBILO®), a subcutaneously administered anti-proprotein convertase subtilisin/kexin type 9 enzyme(PCSK9) monoclonal antibody, is being developed by Innovent for the treatment of hypercholesterolemia and mixed hyperlipidemia. Tafolecimab was approved in August 2023 in China as an adjunct to diet, in combination with a statin or statin with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, for the treatment of adults with primary hyperlipidemia [including heterozygous familial hypercholesterolemia (HeFH) and non-familial hypercholesterolemia (non-FH)] and mixed dyslipidemia who have failed to achieve LDL-C goals despite moderate or higher doses of statins, to reduce LDL-C, total cholesterol (TC), and apolipoprotein B (ApoB) levels. This article summarizes the milestones in the development of tafolecimab leading to this first approval for the treatment of adults with primary hyperlipidemia and mixed dyslipidemia.

Tafolecimab in Chinese patients with non-familial hypercholesterolemia (CREDIT-1): a 48-week randomized, double-blind, placebo-controlled phase 3 trial

Tafolecimab, a fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody developed for the treatment of hypercholesterolemia, demonstrated robust lipid-lowering efficacy and favorable safety in previous short-term studies. We aimed to assess the long-term efficacy and safety of tafolecimab in Chinese non-familial hypercholesterolemia (non-FH) patients. Non-FH patients at high or very-high cardiovascular risk with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8mmol/L or non-FH patients with screening LDL-C level ≥3.4mmol/L and on stable lipid-lowering therapy for at least 4 weeks, were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 450mg Q4W, tafolecimab 600mg Q6W, placebo 450mg Q4W, or placebo 600mg Q6W, respectively, in the 48-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. A total of 618 patients were randomized and 614 patients received at least one dose of tafolecimab (n=411) or placebo (n=203). At week 48, tafolecimab induced significant reductions in LDL-C levels (treatment differences versus placebo [on-treatment estimand]:-65.0% [97.5% CI:-70.2%,-59.9%] for 450mg Q4W;-57.3% [97.5% CI:-64.0%,-50.7%] for 600mg Q6W; both P<0.0001). Significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C < 1.8mmol/L, and LDL-C < 1.4mmol/L than placebo group at both dose regimens (all P<0.0001). Furthermore, tafolecimab significantly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. The most commonly-reported treatment emergent adverse events in the tafolecimab groups included upper respiratory infection, urinary tract infection and hyperuricemia. Tafolecimab dosed at 450mg Q4W and 600mg Q6W was safe and showed superior lipid-lowering efficacy versus placebo, providing a novel treatment option for Chinese hypercholesterolemia patients. This study was sponsored by Innovent Biologics, Inc.

Aortic Wall Thickness as a Surrogate for Subclinical Atherosclerosis in Familial and Nonfamilial Hypercholesterolemia: Quantitative 3D Magnetic Resonance Imaging Study and Interrelations with Computed Tomography Calcium Scores, and Carotid Ultrasonography.

We aimed to compare the extent of subclinical atherosclerosis in the ascending and descending aortas by measuring wall area and thickness using 3D cardiovascular magnetic resonance imaging (aAWAI and dAWAI) in patients with asymptomatic familial hypercholesterolemia (FH) and nonfamilial hypercholesterolemia (NFH). We also aimed to establish the interrelations of CMR parameters with other subclinical atherosclerosis measurements, such as calcium scores, obtained using computed tomography in coronary arteries (CCS) and ascending and descending aorta (TCSasc and TCSdsc), as well as the carotid intima-media thicknesses (cIMT) using ultrasonography. A total of 60 patients with FH (29 men and 31 women), with a mean age of 52.3 ± 9.6 years, were analyzed. A subclinical atherosclerosis assessment was also performed on a group consisting of 30 age- and gender-matched patients with NFH, with a mean age of 52.5 ± 7.9 years. We found the ascending and descending aortic wall areas and thicknesses in the FH group to be significantly increased than those of the NFH group. A multivariate logistic regression analysis showed that a positive FH mutation value was a strong predictor of high aAWAI and dAWAI independent of the LDL cholesterol level. Correlations across CMR atherosclerotic parameters, calcium scores, and cIMT in the FH and NFH groups, were significant but low. Most of the atherosclerosis tests with high results belonged to the FH group. We found that patients with documented heterozygous FH had a higher atherosclerosis burden in the aorta compared to patients with severe hypercholesterolemia without FH gene mutation. Atherosclerosis is not severe in asymptomatic patients with FH, but is more pronounced and also more diffuse than in patients with NFH. The etiology of hypercholesterolemia, and not just cholesterol levels, plays a significant role in determining the degree of subclinical atherosclerosis.

Tafolecimab in Chinese Patients With Hypercholesterolemia (CREDIT-4): A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial

BackgroundTafolecimab is a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, developed for the treatment of hypercholesterolemia. ObjectivesThe purpose of this study was to assess the efficacy and safety of tafolecimab in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. MethodsPatients with diagnoses of heterozygous familial hypercholesterolemia (HeFH) by the Simon Broome criteria or at high or very high cardiovascular risk with nonfamilial hypercholesterolemia, with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L, were randomized 2:1 to receive tafolecimab or placebo 450 mg every 4 weeks (Q4W) in the 12-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. ResultsA total of 303 patients were enrolled and received at least 1 dose of tafolecimab (n = 205) or placebo (n = 98). The least squares mean percent change in LDL-C level from baseline to week 12 was –68.9% (SE 1.4%) in the tafolecimab group and –5.8% (1.8%) in the placebo group (difference: –63.0%; [95% CI: –66.5% to –59.6%]; P < 0.0001). More patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C <1.8 mmol/L, and LDL-C <1.4 mmol/L at week 12 than did those in the placebo group (all P < 0.0001). Furthermore, tafolecimab markedly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. During the double-blind treatment period, the most commonly reported adverse events included urinary tract infection (5.9% with tafolecimab vs 4.1% with placebo) and hyperuricemia (3.4% vs 4.1%). ConclusionsTafolecimab was safe and showed robust lipid-lowering efficacy in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. (A Study of IBI306 in Participants With Hypercholesterolemia; NCT04709536)

PCSK9 inhibitors and incidence of arrhythmias in clinical practice: a phase IV multicentric study

Abstract Funding Acknowledgements Type of funding sources: None. Background PCSK9 inhibitors (PCSK9i) are a novel drug class indicated for the treatment of dyslipidaemia. PCSK9i have been shown to remarkably reduce cardiovascular events in patients at high risk, but little data is currently available regarding the incidence of atrial fibrillation, no reports exist on ventricular events or other cardiac arrhythmias, and is not documented if this drug class is safe regarding arrhythmias as a potential side effect. Purpose To study the incidence of arrhythmias in patients before and after treatment with PCSK9i. Methods All consecutive patients starting treatment with PCSK9 inhibitors, either evolocumab or alirocumab, were consecutively enrolled in two high-volume Italian arrhythmia centres. All patients were treated according to ESC guidelines for primary and secondary prevention. All patients failed to achieve the recommended LDL goals with standard treatment before the introduction of PCSK9i. Patients with familial hypercholesterolemia were excluded. All arrhythmic endpoints were collected in a one-year time frame before and after the first dose of PCSK9i. Results 191 patients were enrolled (mean age 63±15 years, 76.6% males) and followed up for one year. 13.2% were labelled as "statin-intolerant" and were treated only with ezetimibe, all the others had PCSK9i prescription on top of both statin and ezetimibe. The recommended LDL threshold was reached in 45.1% of patients at very high-risk and 76.7% at high-risk. 14.9% of all patients had a history of PACs and 15.6% had a history of PVCs. 7.8% had a previous diagnosis of atrial fibrillation, 2.1% of TRNAV and 6.4% of sustained ventricular arrhythmias. These 6.4% all had an ICD implanted for secondary prevention, while another 0.9% had a primary prevention indication. The total number of PACs in 24 hours decreased from 1260 to 800, although the difference was not statistically significant (p=0.058). Similar results were noted for PVCs (from 271 to 195 in 24 hours; p=0.089). The one-year incidence was 6.1% for atrial fibrillation, 2.3% for TRNAV and 3.8% for sustained ventricular arrhythmias, with no difference between the year before (all p=NS). Of all patients with an ICD and a history of appropriate ICD therapies (n=11, 5.7%) only one experienced appropriate therapies in the year after PCSK9i started. Conclusions The treatment with PCSK9 inhibitors does not significantly modify the risk of supraventricular or ventricular arrhythmias in patients with non-familial hypercholesterolemia. Preliminary data support the safety of this class of drug also regarding arrhythmic events.

219 ISOLATED CORONARY OSTIAL STENOSIS DUE TO RECURRENT AORTIC WALL THROMBOSIS

Abstract Background Coronary ostial lesions are a rare entity and isolated coronary ostial stenosis is even less frequent. Diffuse coronary artery atherosclerosis is the main cause for the non-isolated stenosis, based on old post-mortem series and histological analysis of tissue removed during atherectomies. Case presentation A 49-year-old woman suffering from mild non-familial hypercholesterolemia reported to her family physician repeated episodes of chest pain related to exercise. During a cardiological outpatient evaluation, 12 lead electrocardiogram (ECG) and echocardiography turned out normal. During a stress test she had recurrent chest pain coupled with ECG ischemic changes (diffuse ST segment elevation). She was immediately referred to the emergency department where the ECG was back to normal and the troponin dosage within normal range. Coronary angiography was performed: non-selective cannulation revealed some irregularities of the aortic wall profile at the level of the right coronary ostium, with inability to visualize the right coronary artery. The selective cannulation of the left main coronary artery (LMCA), left anterior descending (LAD) and left circumflex branches showed a critical ostial stenosis at the origin of the LMCA without any other relevant lumen restriction, in a left-dominant pattern of coronary circulation. A suspicion of LAD dissection was raised when a laminar flux was observed at its origin. At the end of the procedure, the patient suddenly collapsed. The recorded rhythm was initially bradycardia, evolving to episodes of ventricular tachycardia for which multiple shocks were applied. Despite the resuscitation efforts, the patient never recovered. Autopsy was performed at the local hospital. At gross analysis, a non-uniform pale-tan thickening at the level of the sino-tubular junction was evident with involvement of both the right and left coronary ostia. Histological examination allowed to ascribe the thickening to recurrent thrombosis, without any underlying inflammatory process at the level of the aortic wall and with only minimal atherosclerotic plaques. No coronary artery dissection nor significant stenosis was present in all the coronary tree. Regarding the ventricular myocardium, one focus of replacement-type fibrosis was identified at subendocardial level in the infero-septal wall coupled with a small spot of loose connective tissue rich in hemosiderin-laden macrophages in the same region, consistent with an area of subacute ischemic damage. Conclusion Several series reported a higher frequency of isolated coronary ostial stenosis in women versus men. In fact, female sex along with hypertriglyceridemia have been recognized as independent risk factors for ostial lesions. The case herein reported highlights the diagnostic relevance of the autopsy investigation together with clinicopathological correlation, particularly in cases where the definite diagnosis can't be achieved in vivo.

Lipid-lowering efficacy and safety of alirocumab in a real-life setting in France: Insights from the ODYSSEY APPRISE study

BackgroundRecently, a multicentre, prospective, single-arm, phase 3b, open-label trial was conducted to determine the safety and efficacy of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting. This study enrolled patients at high cardiovascular risk, with heterozygous familial hypercholesterolaemia (HeFH) or non-familial hypercholesterolaemia (non-FH). Results showed that alirocumab was well tolerated and resulted in a clinically significant reduction in low-density lipoprotein cholesterol (LDL-C). AimThis ancillary analysis aimed to describe the characteristics of the French patients enrolled in the study, the main results observed in this population according to their familial hypercholesterolaemia status, and adherence to treatment. MethodsFrench data were analysed separately from the original dataset of the study. ResultsAmong 215 French patients in the ODYSSEY APPRISE trial, 63.7% had non-FH, with a mean LDL-C concentration of 5.0±1.8mmol/L at baseline. The mean duration of alirocumab exposure was 72.4±42.5 weeks, with only 48.4% of patients receiving statins concomitantly. At week 12, a mean reduction in LDL-C of 56.5±17.8% was observed: 51.2±22.8% in HeFH; 59.5±13.2% in non-FH. This improvement in LDL-C started from week 4 and remained stable and sustained until week 120 in both populations. The overall incidence of severe treatment-emergent adverse events (TEAEs) was 33.5%. The most frequent TEAEs were myalgia (15.8%) and asthenia (15.3%). No tolerance or efficacy differences were observed between patients with or without established coronary artery disease or other cardiovascular disease, whatever the age of these events or considering the concomitant use of other lipid-lowering therapies. ConclusionsIn the French setting, alirocumab was well tolerated, safe and highly effective at reducing LDL-C. These findings support the use of alirocumab to manage hypercholesterolaemia in patients at high cardiovascular risk.

Abstract 10111: Efficacy and Safety of Tafolecimab in Chinese Patients With Non-Familial Hypercholesterolemia (CREDIT-1): A 48-Week Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial

Introduction: Currently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies demonstrated robust low density lipoprotein cholesterol (LDL-C)-lowering efficacy at doses up to 420 mg monthly, while longer dosing intervals are largely unexplored. We assessed the efficacy and safety of tafolecimab, a potential long-acting fully human PCSK9 monoclonal antibody, in Chinese patients with non-familial hypercholesterolemia (ClinicalTrials.gov, NCT04289285). Methods: Patients were randomized 2:2:1:1 to receive subcutaneous tafolecimab 450 mg every 4 weeks (Q4W), tafolecimab 600 mg every 6 weeks (Q6W), placebo Q4W or placebo Q6W for 48 weeks. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Secondary endpoints included proportion of patients achieving ≥50% LDL-C reductions, LDL-C &lt;1.8 mmol/L and LDL-C &lt;1.4 mmol/L. Results: A total of 618 patients (mean LDL-C level 2.85 mmol/L; 9.3% on ezetimibe; 72.8% at very-high cardiovascular risk) were randomized. Of 614 patients receiving at least one dose of the study treatment, 568 (92.5%) completed the study. At both dose regimens, tafolecimab treatment induced significant reductions in LDL-C levels, and significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C &lt;1.8 mmol/L and LDL-C &lt;1.4 mmol/L compared with corresponding placebo groups ( Table ). Meanwhile, significant reductions in non-high density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) levels were achieved with tafolecimab versus placebo at week 48. The most commonly-reported treatment-emergent adverse events were upper respiratory tract infection, urinary tract infection and hyperuricemia. Conclusions: Tafolecimab administered at either 450 mg Q4W or 600 mg Q6W yielded significant and durable reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with non-familial hypercholesterolemia.

The impact of gene variants on the thickness and softness of the Achilles tendon in familial hypercholesterolemia

Background and aimsFamilial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL)-cholesterol, xanthoma of the Achilles tendon (AT), and premature coronary artery disease (CAD). Ultrasonography can assess AT thickness and softness, making it useful for evaluating AT in FH diagnosis. We aimed to clarify whether FH-causative LDLR or PCSK9 variants affect AT thickness or softness. MethodsIn total, 248 FH and 60 non-familial hypercholesterolemia (non-FH) patients (total: 308) aged ≥30 years were enrolled. Patients with FH were classified according to genotype. AT thickness and elasticity index (EI) as softness were measured by ultrasonography. ResultsIn FH patients with LDLR variants, AT was significantly thicker and softer than it was in FH patients with PCSK9 variants, FH patients without LDLR or PCSK9 variants, and patients with non-FH. The proportion of patients harboring LDLR variants significantly increased with AT thickness (p = 2.0 × 10−31) and softness (p = 1.4 × 10−18). Among those with AT thickness>8.5 mm and EI < 3.9, patients with LDLR variants accounted for 89% and 83%, respectively. The odds of AT thickening, AT softening and CAD increased 13.3-fold, 4.9-fold, and 2.1-fold, adjusted for the LDL-C year score by the presence of LDLR variants compared with those of patients without LDLR or PCSK9 variants. PCSK9 variants did not influence AT thickening or softening or CAD prevalence. ConclusionsLDLR variants affected AT thickness and softness independent of the LDL-C year score, but PCSK9 variants did not. Evaluating AT is important for identifying FH patients with LDLR variants at high risk for CAD.

Evaluation of the Therapeutic Pattern and Pharmaco-Utilization in Hypercholesterolemic Patients Treated with Statins: A Retrospective Study on Italian Real-World Data.

PurposeThe study aimed to analyze, in hypercholesterolemic patients under statin medication, patient characteristics and their lipid profile at baseline, the therapeutic pathway, and the pharmaco-utilization, using real-world data in Italy.Patients and MethodsA retrospective study was conducted using administrative databases of a sample of entities covering 6.5 million health-assisted individuals. Between January 2010 and June 2019, patients with non-familial hypercholesterolemia (nFH) were identified by 1) ≥1 low-density lipoprotein cholesterol (LDL-C) measurement (LDL-C assessment date was the index-date) and 2) statin prescription during 6 months before the index-date (pharmaco-utilization period). FH patients were defined by LDL-C evaluation, statin treatment during the pharmaco-utilization period, and a score ≥6 according to the Dutch Lipid Clinic Network criteria. nFH patients were divided into four exclusive cohorts based on CV-risk class: 1) with previous CV disease (CVD); 2) with diabetes mellitus; 3) with mixed-dyslipidemia diagnosis; 4) in primary-prevention. Based on LDL-C index values, patient was defined with LDL-C “controlled” if its levels were ≤70mg/dl (CVD), ≤100mg/dl (diabetes, FH), ≤130mg/dl (mixed-dyslipidemia, primary-prevention).ResultsOverall 164,161 nFH patients were included (mean age 72 years, 51% male); of these, 46,782 (28.5%) were CVD (mean age 74 years, 66% male), 34,803 (21.2%) were diabetic (mean age 72 years, 51% male), 1617 (1%) were with mixed-dyslipidemia (mean age 71 years, 48% male) and 80,959 (49.3%) were in primary-prevention (mean age 71 years, 42% male). The proportion of nFH patients with controlled LDL-C was 41.2% for CVD, 73.6% for diabetic, 80.7% for mixed-dyslipidemia, and 79.5% for primary-prevention patients; 49% of nFH patients were adherent to therapy. Overall, 1287 FH patients (mean age 64 years, 42% male) were included; in 39.2% of the patients, LDL-C was controlled, and 44% of the patients were adherent to therapy.ConclusionThe results of this study highlighted non-optimal therapeutic management of hypercholesterolemic patients in Italian clinical practice, with a notable quote of patients non-adherent to therapy.

Inclisiran (Leqvio)

&#x0D; CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.&#x0D; The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.&#x0D; This review assesses inclisiran (Leqvio), 284 mg in 1.5 mL (189 mg/mL) solution for SC injection.&#x0D; Indication: As an adjunct to lifestyle changes, including diet, to further reduce low-density lipoprotein cholesterol (LDL-C) level in adults with the following conditions who are on a maximally tolerated dose of a statin, with or without other LDL-C-lowering therapies:&#x0D; &#x0D; heterozygous familial hypercholesterolemia (HeFH), or&#x0D; non-familial hypercholesterolemia with atherosclerotic cardiovascular disease.&#x0D; &#x0D; &#x0D;

Inclisiran (Leqvio)

&#x0D; CADTH recommends that Leqvio should not be reimbursed by public drug plans as an adjunct to lifestyle changes, including diet, to further reduce low-density lipoprotein cholesterol (LDL-C) levels in adults who are on a maximally tolerated dose of a statin, with or without other LDL-C–lowering therapies, and who have heterozygous familial hypercholesterolemia (HeFH) or non-familial hypercholesterolemia (nFH) with atherosclerotic cardiovascular disease (ASCVD).&#x0D; Evidence from 3 clinical trials showed that treatment with Leqvio lowered bad cholesterol (LDL-C) in adults with HeFH or nFH with ASCVD who were already being treated with the highest possible dose of statins and in those who cannot tolerate treatment with statins.&#x0D; Patients identified a need for treatments that can reduce bad cholesterol (LDL-C) and cardiovascular morbidity and death; however, there was not enough evidence to show that Leqvio would reduce cardiovascular morbidity and death. Results from 2 ongoing studies (ORION-4 and ORION-8) will contribute valuable information regarding the long-term safety and efficacy of Leqvio when results become available.&#x0D;

Novel insights into the management of German patients with very high cardiovascular risk eligible for PCSK9 inhibitor treatment: baseline characteristics from the PERI-DYS study

Abstract Background The reasons why patients are treated or not with PCSK9 inhibitors (PCSK9i) are incompletely understood. In Germany, access to PCSK9i is limited by local regulations and many high-risk cardiovascular patients do not receive these therapies. The PERI-DYS study aims to describe and compare two groups of dyslipidaemia patients at very high CV risk: those treated with PCSK9i compared with patients qualifying for but not treated with PCSK9i. Methods Observational study with up to 2000 consented patients, documented mainly by office-based cardiologists or physicians in lipid ambulances with data extracted from patient charts. Lipid lowering treatment (LLT) at enrolment includes ongoing PCSK9i use, newly initiated PCSK9i, statins, ezetimibe, and lipoprotein apheresis. Patients are followed for up to 3 years, with visits every 6±2 months to record LLT (drugs, dosing), other CV medications, lipid and glucose values, blood pressure, clinical events (major adverse cardiac and cerebrovascular events) and adverse drug reactions. Results As of 05 March 2021, 1488 patients have been enrolled across 70 sites. The majority of patients (91.5%) had heterozygous familial or non-familial hypercholesterolemia or mixed dyslipidaemia. At enrolment, 49.4% of patients were receiving PCSK9i (35.4% ongoing and 14.0% newly treated). Among PCSK9i users, the majority were receiving evolocumab 140 mg (n=567, 38.1% of all enrolled patients). There were no major differences in demographics and non-lipid lowering medication, with the exception of more females in the PCSK9i group. The estimated untreated LDL-C based on “back-calculation” was higher in patients who were on ongoing PCSK9i therapy than in those not on PCSK9i or newly treated with PCSK9i (Table 1). Physician-reported statin intolerance was much more common in the two PCSK9i groups compared with the non-PCSK9i group (67% versus 14%). Patients in the PCSK9i groups received fewer concomitant statins. Mean on-treatment total cholesterol and LDL-C were considerably lower in patients who were on ongoing PCSK9i compared to non-PCSK9i. Overall, nicotinic acid, fibrates, cholestagel, and omega-3 fatty acids were rarely used (data not shown). Conclusions Patients treated with PCSK9i and those qualifying for but not treated with PCSK9i had similar baseline characteristics, but the former had higher estimated untreated LDL-C values and a higher rate of statin intolerance. Ongoing follow-up will determine the prognostic importance of these findings. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen GmbH Germany

The Effect of LRP-1 Gene and Mir-205 on Cardiovascular Disease in Iraqi Patients with Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is a genetic disorder characterized by autosomal inheritance in genes related to LDL-C metabolism, with the major clinical features of hyper-LDL-cholesterolemia and premature coronary artery disease. (LRP-1) is a member of the LDLR family. It is a membrane receptor with scavenging and signaling properties. LRP-1 interacts with a wide range of extracellular ligands as well as intracellular scaffolding and signaling proteins, which makes it important in crucial clinical circumstances like cardiovascular disease, cancer, and neurological illnesses. Mir-205 uses these molecules as biomarker for cardiovascular diseases. This study aims to measure gene expression for the LPR-1 gene and its relationship to the development of cardiovascular disease in familial hypercholesterolemia and non-familial hypercholesterolemia. Also, it studies the indication whether mir-205 regulates the action of the LRP-1 gene in terms of increasing or decreasing gene expression. However, the available methods for measuring LRP1 levels are direct and quantitative using Poly Chain Reaction (RT-PCR) in real time, not at its ends. In the present study, blood was isolated from 150 individuals distributed into three groups: Group 1 included: 50 samples from a healthy group; Group 2: 50 samples from non-Familial hypercholesterolemia patients; Group 3:50 samples Familial hyperchol-esterolemia patients. The results showed that LRP1 protein expression was significantly reduced in patients with F.H compared with normal control in a small cohort from an Iraqi population. This pilot study suggests that the reduced LRP1 protein expression may be associated with cardiovascular disease progression.

Impact of PCSK9 inhibitors on hypercholesterolaemic patients at a tertiary centre lipid clinic

Background and Aims: Elevated low-density lipoprotein cholesterol (LDL-C), which arises due to genetic and environmental factors, has a causal role in the pathogenesis of cardiovascular disease (CVD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are approved for patients with familial hypercholesterolaemia (FH) and patients at high risk of CVD due to non-familial hypercholesterolaemia (non-FH). In clinical trials, PCSK9 inhibitors are well-tolerated and lead to reductions in LDL-C of up to 67%. However, evidence regarding their efficacy and tolerability in real-world clinical practice remains scarce. This study aimed to evaluate the efficacy and tolerability of PCSK9 inhibitors at Imperial College Healthcare Trust (ICHT) lipid clinic.

The economic impact of hypercholesterolemia and mixed dyslipidemia: A systematic review of cost of illness studies.

Hypercholesterolemia is a clinically relevant condition with an ascertained role in atherogenesis. In particular, its presence directly correlates to the risk of atherosclerotic cardiovascular disease (ASCVD). As known, cardiovascular diseases pose a significant economic burden worldwide; however, a clear picture of the economic impact of ASCVD secondary to hypercholesterolemia is lacking. This study aiming at conducting a systematic review of the current literature to assess the economic impact of familial hypercholesterolemia (FH), non-familial hypercholesterolemia (non-FH) or mixed dyslipidemia. A literature search was performed in Medline/PubMed and Embase database up to September 1st, 2020, exploring evidence published from 2010. The literature review was conducted in accordance with PRISMA guidelines. To be included the studies must be conducted on people who have been diagnosed with familial hypercholesterolemia, non-familial hypercholesterolemia or mixed dyslipidemia, and report data/information on costs attributable to these conditions and their sequelae. A total of 1260 studies were retrieved. After reading the titles and abstract, 103 studies were selected for full reading and eight met the criteria for inclusion. All but one studies were published in the American continent, with the majority conducted in US. An observational design with a prevalence approach were used and all estimated the economic burden of CVD. Direct cost estimates as annual average health expenditure on all population, ranging from $17 to $259 million. Few studies assessing the economic impact of hypercholesterolemia are available in the literature and new researches are needed to provide a more updated and reliable picture. Despite this scarceness of evidence, this review adds important data for future discussion on the knowledge of the economic impact of hypercholesterolemia and costs of care associated to this condition, with important implication for public health researches and novel therapies implementation.

Intensified lipid-lowering treatment with alirocumab in patients with coronary heart disease

BackgroundAtherosclerotic cardiovascular disease is the leading cause of death and disability in the Western world.ObjectiveTo characterise adults with confirmed coronary heart disease (CHD) and primary heterozygous familial or non-familial hypercholesterolaemia...