Evolocumab treatment reduces carotid intima-media thickness in paediatric patients with heterozygous familial hypercholesterolaemia.

Aim: Children with heterozygous familial hypercholesterolaemia (HeFH) show greater carotid intima-media thickness (cIMT). Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody, substantially reduced low-density lipoprotein cholesterol (LDL-C) and modestly reduced lipoprotein(a) in children with HeFH. We investigated evolocumab's effect on cIMT progression.

Detecting familial hypercholesterolemia: An observational study leveraging mandatory universal pediatric total cholesterol screening in Slovakia.

Background: In Slovakia, a mandatory national universal pediatric total cholesterol (TC) screening program is in place to identify cases of familial hypercholesterolemia (FH). However, the program's effectiveness has not been systematically assessed.

Objective: This study aimed to estimate the prevalence of FH among parents of children that had elevated TC levels identified during screening.

Evolocumab-Based LDL-C Management in High and Very High Cardiovascular Risk Patients in German Clinical Practice: The HEYMANS Study.

Introduction: Low-density lipoprotein cholesterol (LDL-C) is among the most important modifiable risk factors for cardiovascular disease. In very high-risk patients, the European Society of Cardiology/European Atherosclerosis Society guidelines recommend attaining LDL-C < 55 mg/dL. In the German cohort of the observational HEYMANS study, we aimed to describe the clinical characteristics and LDL-C control among patients initiating evolocumab.

Evolocumab use in clinical practice in Switzerland: final data of the observational HEYMANS cohort study.

Aims: The HEYMANS study observed patients receiving evolocumab as part of routine clinical hyperlipidemia management. It was designed to capture data on clinical parameters relevant to health authorities and physicians.

Methods: This was a European multi-country observational cohort serial chart review study; data on the Swiss cohort are reported here.

Evolocumab effectiveness in the real-world setting: Austrian data from the pan-European observational HEYMANS study.

Background: This real-world study examined clinical characteristics and dyslipidemia management among patients initiating evolocumab across 12 European countries. Austrian data are reported.

Methods: Data of consenting adults were collected for ≤ 6 months prior to evolocumab initiation (baseline) and ≤ 30 months post-initiation.

Long-term treatment persistence and maintained reduction of LDL-cholesterol levels with evolocumab over 30 months: Results from the Spanish cohort of the European prospective HEYMANS study.

Aims: Limited data exist on low-density lipoprotein-cholesterol (LDL-C) level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. HEYMANS (NCT02770131) is the first multi-country, multicenter, observational study of European patients initiating evolocumab as part of their routine clinical management, based on local reimbursement criteria (overall data recently published). The aim of this analysis is to describe clinical characteristics, baseline and changes in LDL-C levels, treatment patterns and persistence to evolocumab over 30 months in the Spanish cohort using data from the HEYMANS Registry.

Evolocumab is Initiated in Central and Eastern Europe at Much Higher LDL-C Levels Than Recommended in Guidelines: Results from the Observational HEYMANS Study.

We examined clinical characteristics and low-density lipoprotein cholesterol (LDL-C) lowering in patients initiating evolocumab in real-world practice in a Central and Eastern European (CEE) cohort from the pan-European HEYMANS study. Patients from Bulgaria, Czech Republic, and Slovakia were enrolled at initiation of evolocumab (baseline) as per local reimbursement criteria. Demographic/clinical characteristics, lipid-lowering therapy (LLT) and lipid values were collected from medical records for ≤6 months before baseline and ≤30 months after evolocumab initiation.

Long-term persistence with evolocumab treatment and sustained reductions in LDL-cholesterol levels over 30 months: Final results from the European observational HEYMANS study.

Background And Aims: Variability in low-density lipoprotein-cholesterol (LDL-C) level control at a population level is associated with poor cardiovascular outcomes. Limited data exist on LDL-C level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. Using data from the HEYMANS registry, this analysis aimed to assess evolocumab persistence and discontinuation over 30 months of evolocumab treatment and to evaluate at a population level the variability in LDL-C level reductions during the study period.

Cognitive function with evolocumab in pediatric heterozygous familial hypercholesterolemia.

Background: Evolocumab is a fully human monoclonal antibody inhibitor of PCSK9 approved for lowering low-density lipoprotein cholesterol in adults and pediatric patients with familial hypercholesterolemia (FH). The cognitive safety of evolocumab has been established in adults but has not yet been described in pediatric patients.

Objective: To determine the effects of evolocumab on cognitive function in pediatric heterozygous FH.

Low-density lipoprotein cholesterol levels exceed the recommended European threshold for PCSK9i initiation: lessons from the HEYMANS study.

Aims: To describe the characteristics of patients receiving evolocumab in clinical practice across 12 European countries and simulate the association between low-density lipoprotein cholesterol (LDL-C) reduction and cardiovascular (CV) risk reduction.

Methods And Results: The characteristics of hyperlipidaemic patients at initiation of evolocumab and treatment patterns study-HEYMANS (n = 1952) is a prospective registry of patients ≥18 years old who initiated evolocumab from 1 August 2015 onwards. Mean (standard deviation) age was 60 (10.

Management of Hyperlipidemia in Very High and Extreme Risk Patients in Croatia: an observational study of treatment patterns and lipid control.

Our observational study evaluated current management of elevated low-density lipoprotein cholesterol (LDL-C) in adult secondary prevention patients (all very high risk (VHR) by European guidelines) attending specialist clinics across Croatia. Data were collected retrospectively from patient records for the preceding 12 months. The subset judged to be at extreme risk (ER; American Association of Clinical Endocrinologists (AACE) criteria; n=48) were compared with the remaining patients (VHR group; n=41).

Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia.

Background: Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known.

Methods: We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia.

Clinical Management of High and Very High Risk Patients with Hyperlipidaemia in Central and Eastern Europe: An Observational Study.

Introduction: A retrospective/prospective observational study was conducted to explore the current management of hyperlipidaemia in high-risk (HR) and very high risk (VHR) patients in central/eastern Europe and Israel.

Methods: The study enrolled adult patients who were receiving lipid-lowering therapy and attending a specialist (cardiologist/diabetologist/lipidologist) or internist for a routine visit at 57 sites (including academic/specialist/internal medicine centres) across Bulgaria, Croatia, Czech Republic, Israel, Poland, Romania and Slovakia. Data were collected from medical records, for the 12 months before enrolment, with/without ≤ 6 months' additional prospective follow-up.

Long-term safety, tolerability, and efficacy of evolocumab in patients with heterozygous familial hypercholesterolemia.

Background: Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9, is safe and effective when dosed biweekly (Q2W) or monthly (QM) in patients with heterozygous familial hypercholesterolemia (HeFH) as demonstrated in two 12-week trials: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3).

Objective: The objective of the study was to evaluate long-term efficacy, safety, and tolerability of evolocumab during open-label extension trials.

Methods: Patients completing parent trials were re-randomized 2:1 to evolocumab plus standard of care (SOC) or SOC alone for 52 weeks (Open-Label Study of Long-term Evaluation Against LDL-C [OSLER-1]) or 48 weeks (OSLER-2).

Systematic Review and Network Meta-Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia.

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when added to statin therapy in patients who need additional LDL-C reduction.

Methods And Results: We conducted a systematic review and network meta-analysis of randomized trials of lipid-lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid-lowering therapies that enrolled patients requiring further LDL-C reduction while on maximally tolerated medium- or high-intensity statin, of which 15 could be relevant for inclusion in LDL-C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms.

Efficacy and Safety of the PCSK9 Inhibitor Evolocumab in Patients with Mixed Hyperlipidemia.

Purpose: Evolocumab significantly reduces low-density lipoprotein-cholesterol (LDL-C); we investigated its effects on LDL-C lowering in patients with mixed hyperlipidemia.

Methods: We compared the efficacy and safety of evolocumab in hypercholesterolemic patients selected from the phase 2 and 3 trials who had fasting triglyceride levels ≥1.7 mmol/L (150 mg/dL elevated triglycerides) and <1.

Effects of Evolocumab on Vitamin E and Steroid Hormone Levels: Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study.

Rationale: Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels.

Objective: To determine the effects of evolocumab on vitamin E and steroid hormone levels.

Methods And Results: After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C ≥2.

PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial.

Background: Heterozygous familial hypercholesterolaemia is characterised by low cellular uptake of LDL cholesterol, increased plasma LDL cholesterol concentrations, and premature cardiovascular disease. Despite intensive statin therapy, with or without ezetimibe, many patients are unable to achieve recommended target levels of LDL cholesterol. We investigated the effect of PCSK9 inhibition with evolocumab (AMG 145) on LDL cholesterol in patients with this disorder.

Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism.

Background: Treatment with cinacalcet improves the control of secondary hyperparathyroidism (SHPT) and the achievement of calcium and phosphorus targets. Most data come from subjects receiving cinacalcet after several years of dialysis treatment. We therefore compared the efficacy of treatment with cinacalcet and low doses of active vitamin D to flexible doses of active vitamin D alone for the management of SHPT in patients recently initiating haemodialysis.

Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial.

Background: Despite statin treatment, many patients with heterozygous familial hypercholesterolemia do not reach desired low-density lipoprotein cholesterol (LDL-C) targets. AMG 145, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease, demonstrated significant reductions in LDL-C in phase 1 studies. This phase 2, multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluated the efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia patients.

An observational cohort study of extended dosing (once every 2 weeks or once monthly) regimens with darbepoetin alfa in patients with chronic kidney disease not on dialysis: the EXTEND study.

Background: Darbepoetin alfa (DA) has been shown to be an effective treatment of anaemia in patients with chronic kidney disease (CKD) not on dialysis (NoD). EXTEND is an observational study assessing the effectiveness of DA administered once biweekly (Q2W) or monthly (QM) in a general CKD-NoD population.

Methods: Adult CKD-NoD patients starting DA Q2W/QM treatment in June 2006 or later were eligible.

Extended dosing of darbepoetin alfa in peritoneal dialysis patients.

Background: Anemia is common among peritoneal dialysis (PD) patients, and most patients require erythropoiesis-stimulating agents (ESA) to maintain their hemoglobin concentrations within current guideline recommendations. Darbepoetin alfa is an ESA with a 3-fold longer half-life and greater in vivo biological activity than recombinant human erythropoietin, allowing less frequent dosing that may simplify anemia management in these patients, providing benefits to patients, care givers and health care providers. Clinical studies have confirmed the efficacy and safety of darbepoetin alfa administered at extended dosing intervals.

Paroxetine controlled release for premenstrual dysphoric disorder: a double-blind, placebo-controlled trial.

Background: Better characterization of safety and efficacy of multiple doses of selective serotonin reuptake inhibitors for the treatment of a wider range of symptoms of premenstrual dysphoric disorder (PMDD) will provide clinicians with flexibility to provide symptom relief along with acceptable tolerability. This study was designed to assess the efficacy and tolerability of multiple doses of paroxetine controlled release (CR) in PMDD.

Methods: In a multicenter (43 outpatient U.