scholarly journals Screening and treatment of familial hypercholesterolemia in a French sample of ambulatory care patients: A retrospective longitudinal cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255345
Author(s):  
Jean Ferrières ◽  
Victoria Banks ◽  
Demetris Pillas ◽  
Francesco Giorgianni ◽  
Laurene Gantzer ◽  
...  
Keyword(s):  
Ambulatory Care ◽  
Familial Hypercholesterolemia ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Moderate Intensity ◽  
Health Improvement ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Pharmacological Management

Background and aims Untreated Familial Hypercholesterolemia (FH) leads to premature morbidity and mortality. In France, its epidemiology and management are understudied in ambulatory care. We described the clinical profile, pharmacological management, and clinical outcomes in a French sample of FH patients. Methods This was a retrospective longitudinal study on patients from The Health Improvement Network (THIN®) database in France, between October 2016-June 2019. Patients ≥18 years, with probable/definite FH based on the Dutch Lipid Clinic Network (DLCN) criteria were included. Baseline characteristics, lipid profile, lipid-lowering therapy (LLT), low-density lipoprotein-cholesterol (LDL-C) goal achievement; and disease management at 6-month of follow-up were analyzed. Results 116 patients with probable (n = 70)/definite (n = 46) FH were included (mean age:57.8±14.0 years; 56.0% women; 9.5% with personal history of cardiovascular events); 90 patients had data available at follow-up. At baseline, 77.6% of patients had LDL-C>190 mg/dL, 27.6% were not receiving LLTs, 37.9% received statins alone, 20.7% statins with other LLTs, and 7.7% other LLTs. High-intensity statins were prescribed to 11.2% of patients, 30.2% received moderate-intensity statins, and 8.6% low-intensity statins. Only 6.0% of patients achieved LDL-C goal. At 6-month of follow-up, statins discontinuation and switching were 22.7% and 2.3%, respectively. None of the patients received proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors at baseline nor follow-up. Conclusions Despite the existence of effective LLTs, FH patients are suboptimally-treated, do not achieve LDL-C goal, and exhibit worsened pharmacological management over time. Future studies with longer follow-up periods and assessment of factors affecting LDL-C management, including lifestyle and diet, are needed.

scholarly journals Evolocumab use in Europe: clinical guidelines vs. reimbursement thresholds – results from the HEYMANS study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K K Ray ◽  
E Bruckert ◽  
P Filardi ◽  
C Ebenbichler ◽  
A Vogt ◽  
...  
Keyword(s):  
Clinical Guidelines ◽  
Clinical Characteristics ◽  
Lipid Lowering ◽  
Moderate Intensity ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Private Company ◽  
Statin Monotherapy ◽  
Very High

Abstract Background 2019 ESC/EAS guidelines recommend a 50% lowering in untreated LDL-C and use of PCSK9 inhibitors (PCSK9i) for patients (pts) at very high cardiovascular (CV) risk when LDL-C goals of <1.4mmol/L are not met despite maximally tolerated statins and ezetimibe. However, the LDL-C threshold at which PCSK9i are reimbursed are higher than the goals recommended in clinical guidelines. Purpose This prospective observational cohort study describes clinical characteristics and LDL-C control among pts initiating evolocumab across 12 EU countries. Methods Pts are followed from evolocumab initiation (baseline). Demographic/clinical characteristics, lipid lowering therapy (LLT) and lipid values are being collected from medical records (6 months before evolocumab up to 30 months post initiation). We report interim data from pts initiating evolocumab from August 2015 followed-up until July 2020. Results Of the 1,952 pts in whom evolocumab was initiated as per local reimbursement criteria, most (1844 [94%]) had 12 months follow-up, 785 (40%) had 24 months follow-up; mean follow-up: 20 months. Mean (SD) age was 60 (10.8) years; 85% of pts had a history of CV disease, 45% had familial hypercholesterolemia, 19% had type 2 diabetes, 65% were hypertensive, 7% had chronic kidney disease and 51% were prior/current smokers. At evolocumab initiation, 60% reported statin intolerance and 41% were on no background LLT. Fewer than half (846 [43%]) were receiving a statin (± ezetimibe); of these, most received a high/moderate intensity (68%/22%), with 13% receiving statin monotherapy. Median (Q1, Q3) baseline LDL-C was 3.98 (3.17, 5.07) mmol/L. Within 3 months of initiation median LDL-C fell by 58% to 1.63mmol/L. This reduction was maintained over time (Figure 1). Overall, 58% of pts achieved at least one LDL-C <1.4mmol/L during follow-up. Among pts receiving background statins ± ezetimibe at evolocumab initiation, 67% (710/1053) achieved at least one LDL-C <1.4mmol/L, versus 44% (317/714) of pts not receiving background statins/ezetimibe. During follow-up background oral LLT did not materially change; 40–45% pts received no LLT, 41–44% received statin ± ezetimibe, 12–14% received statin monotherapy. Conclusion In Europe, pts initiated on evolocumab had baseline LDL-C levels almost 3x higher than the present threshold for PCSK9i use recommended in guidelines reflecting disparities between local reimbursement criteria and guidelines. Although evolocumab led to a >50% reduction in LDL-C, only ∼50% pts achieved an LDL-C <1.4mmol/L, as approximately 41% received only evolocumab as monotherapy. LDL-C goal attainment was however higher among pts receiving evolocumab with background LLT. Therefore, lowering the LDL-C threshold for PCSK9i reimbursement, would result in more patients receiving combination therapy with oral LLT plus PCSK9i, thus increasing the likelihood of more pts achieving very-high risk LDL-C goals. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen Europe GmbH

P648Screening and treatment of familial hypercholesterolemia in a French sample of ambulatory care: a retrospective longitudinal cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Ferrieres ◽  
V Banks ◽  
D Pillas ◽  
L Ricci ◽  
M Dova-Boivin ◽  
...  
Keyword(s):  
Ambulatory Care ◽  
Familial Hypercholesterolemia ◽  
Clinical Symptoms ◽  
Lipid Lowering ◽  
Health Improvement ◽  
Ambulatory Care Setting ◽  
Lipid Clinic ◽  
Data Division ◽  
The Impact

Abstract Background Familial hypercholesterolemia (FH) is largely underdiagnosed as there are typically no clinical symptoms prior to the first cardiovascular (CV) event. We conducted a study which utilised ambulatory care electronic medical record (EMRs) to alert physicians to possible cases of FH. Specifically, physicians were alerted to LDL-C levels >190 mg/dL (suggesting a risk of FH) and invited to complete the Dutch Lipid Clinic Network score (DLCN). Purpose Describe characteristics, comorbidities and clinical management of patients diagnosed with definite or probable FH in an ambulatory care setting. Methods All patients with a DLCN score of definite/probable FH (score higher or equal than 6; index event) between January 2016 and September 2018 were identified in the THIN® database (The Health Improvement Network; an anonymized EMR powered by GERSDATA, a Cegedim Health Data Division). These fully anonymized data were collected by 2000 General Practitioners (GP), 130 cardiologists and 40 endocrinologists, receiving 5.5 million patients regularly in their office. Sociodemographic, laboratory measurements, comorbidities, lipid-lowering therapies (LLT), visits to specialists, LDL-C and hospitalizations were collected and analysed at baseline, and 1, 2, 3, 6 months, and 1 year thereafter. Results From 999 anonymous patients with a DLCN score, 98 (10%) FH patients were identified (38 [39%] definite FH, 60 [61%] probable FH) while remaining fully anonymous, 9 (9%) of whom already had genetic testing. Mean (SD) age was 57.4 (14.3) years; 56 (57%) patients were female, half (51/98 [52%]) were diagnosed with pure hypercholesterolemia (ICD-10 code: E78.0) and 9 (9%) had a personal history of CV event. 93 patients (95%) had a LDL-C measurement prior to DLCN assessment (definite FH, 36/38 [95%]; probable FH, 57/60 [95%]). Among screened FH patients, 61.2% had LDL-C between 190 to 250 mg/dL and 16.3% had LDL-C higher than 250 mg/dL. At the time of DLCN assessment, one third (30/98 [31%]) of patients were not receiving any LLT, one third ([35%] 34/98) were receiving statins alone, 19% (19/98) receiving LLT combination with statin, and 15% (15) other LLTs. Moderate statin intensity was prescribed in 20% (20/98) of patients; high intensity statin, 17%, (17/98); low intensity, 10% (10/98). No improvement on LLT use (including use of high statin intensity) was observed over the 12-month follow-up. Conclusion This is the first study in France that use EMR to screen possible FH patients and support GPs in identifying patients that need to be treated. Our data highlight the need to screen, diagnosis and treat potential FH patients in ambulatory care settings. Longer follow-up is needed to evaluate the impact of FH assessment on referral to specialists, LLT and clinical outcomes. Acknowledgement/Funding Amgen

scholarly journals Treatment with PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia Lowers Plasma Levels of Platelet-Activating Factor and Its Precursors: A Combined Metabolomic and Lipidomic Approach

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1073
Author(s):  
Alessandro Di Minno ◽  
Roberta Clara Orsini ◽  
Mattia Chiesa ◽  
Viviana Cavalca ◽  
Ilenia Calcaterra ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Platelet Activating Factor ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Pleiotropic Effect ◽  
Untargeted Metabolomics ◽  
Lipid Lowering ◽  
P Value ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors

Introduction: Familial hypercholesterolemia (FH) is characterized by extremely high levels of circulating low-density lipoprotein cholesterol (LDL-C) and is caused by mutations of genes involved in LDL-C metabolism, including LDL receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Accordingly, PCSK9 inhibitors (PCSK9i) are effective in LDL-C reduction. However, no data are available on the pleiotropic effect of PCSK9i. To this end, we performed an untargeted metabolomics approach to gather a global view on changes in metabolic pathways in patients receiving treatment with PCSK9i. Methods: Twenty-five FH patients starting treatment with PCSK-9i were evaluated by an untargeted metabolomics approach at baseline (before PCSK9i treatment) and after 12 weeks of treatment. Results: All the 25 FH subjects enrolled were on maximal tolerated lipid-lowering therapy prior to study entry. After a 12 week treatment with PCSK9i, we observed an expected significant reduction in LDL-cholesterol levels (from 201.0 ± 69.5 mg/dL to 103.0 ± 58.0 mg/dL, p < 0.001). The LDL-C target was achieved in 36% of patients. After peak validation and correction, after 12 weeks of PCSK9i treatment as compared to baseline, we observed increments in creatine (p-value = 0.041), indole (p-value = 0.045), and indoleacrylic acid (p-value= 0.045) concentrations. Conversely, significant decreases in choline (p-value = 0.045) and phosphatidylcholine (p-value < 0.01) together with a reduction in platelet activating factor (p-value = 0.041) were observed. Conclusions: Taking advantage of untargeted metabolomics, we first provided evidence of concomitant reductions in inflammation and platelet activation metabolites in FH patients receiving a 12 week treatment with PCSK9i.

scholarly journals Treatment Inertia in Patients With Familial Hypercholesterolemia

2021 ◽  
Author(s):  
Anatoly Langer ◽  
G. B. John Mancini ◽  
Mary Tan ◽  
Shaun G. Goodman ◽  
Vineeta Ahooja ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Recommended Level

Background We studied care gap in patients with familial hypercholesterolemia (FH) with respect to lipid‐lowering therapy. Methods and Results We enrolled patients with cardiovascular disease (CVD) or FH and low‐density lipoprotein‐cholesterol >2.0 mmol/L despite maximally tolerated statin therapy. During follow‐up physicians received online reminders of treatment recommendations of 2009 patients (median age, 63 years, 42% women), 52.4% had CVD only, 31.7% FH only, and 15.9% both CVD and FH. Patients with FH were younger and more likely to be women and non‐White with significantly higher baseline low‐density lipoprotein‐cholesterol level (mmol/L) as compared with patients with CVD (FH 3.92±1.48 versus CVD 2.96±0.94, P <0.0001). Patients with FH received less statin (70.6% versus 79.2%, P =0.0001) at baseline but not ezetimibe (28.1% versus 20.4%, P =0.0003). Among patients with FH only, 45.3% were at low‐density lipoprotein target (≥ 50% reduction from pre‐treatment level or low‐density lipoprotein <2.5 mmol/L) at baseline and increasing to 65.8% and 73.6% by visit 2 and 3, respectively. Among patients with CVD only, none were at recommended level (≤2.0 mmol/L) at baseline and 44.3% and 53.3% were at recommended level on second and third visit, respectively. When primary end point was analyzed as a difference between baseline and last available follow‐up observation, only 22.0% of patients with FH only achieved it as compared with 45.8% with CVD only ( P <0.0001) and 55.2% with both FH+CVD ( P <0.0001). Conclusions There is significant treatment inertia in patients with FH including those with CVD. Education focused on patients with FH should continue to be undertaken.

scholarly journals FAMILIAL HYPERCHOLESTEROLEMIA: DIAGNOSTIC ISSUES AND THERAPEUTIC POSSIBILITIES

2019 ◽  
Vol 26 (1) ◽  
pp. 175-186
Author(s):  
Vitalii K. Zafiraki ◽  
Alim M. Namitokov ◽  
Elena D. Kosmacheva
Keyword(s):  
Familial Hypercholesterolemia ◽  
Conflict Of Interest ◽  
Screening Program ◽  
Genetic Defect ◽  
Clinical Manifestations ◽  
Density Lipoprotein ◽  
Premature Death ◽  
Lipid Lowering ◽  
Monogenic Disease ◽  
Lipid Lowering Therapy

Familial hypercholesterolemia (FHC) is a common monogenic disease that occurs with a frequency of ~1:250 and is characterised by a high content of low-density lipoprotein (LDL) in the blood. This disease leads to the early development of atherosclerotic cardiovascular diseases (ACVD). Although the screening and diagnostics issues concerned with FHC are well developed and the modern lipid-lowering therapy can significantly improve the prognosis, the detectability of this disease remains extremely low. In recent years, the concept of FHC has undergone significant changes under the influence of large epidemiological studies, including verification of the FHC diagnosis using genetic tests. The article is aimed at discussing the clinical manifestations of FHC, as well as modern medical and extracorporal approaches to its treatment.Conclusion.Until the advent of modern lipid-lowering drugs, FHC had remained to be a disease with a poor prognosis due to early ACVD and the associated premature death. Today, the diseases is amenable to successful treatment, which, though not eliminating the genetic defect, allows almost the same life duration as in the general population to be achieved. However, all the possibilities of modern approaches to the treatment of this serious disease can be realized provided that a state-level screening program for such patients has been implemented.Conflict of interest: the authors declare no conflict of interest.

Abstract 18995: Statins in Familial Hypercholesterolemia - Effects on Coronary Artery Disease and All-cause Mortality

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Joost Besseling ◽  
Gerard K Hovingh ◽  
John J Kastelein ◽  
Barbara A Hutten
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Lipid Lowering ◽  
Premature Coronary Artery Disease ◽  
Lipid Lowering Therapy ◽  
Time Varying ◽  
All Cause Mortality ◽  
Artery Disease

Introduction: Heterozygous familial hypercholesterolemia (heFH) is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary artery disease (CAD) and death. Reduction of CAD and mortality by statins has not been properly quantified in heFH. The aim of the current study is to determine the effect of statins on CAD and mortality in heFH. Methods: All adult heFH patients identified by the Dutch FH screening program between 1994 and 2014 and registered in the PHARMO Database Network were eligible. Of these patients we obtained hospital, pharmacy (in- and outpatient), and mortality records in the period between 1995 and 2015. The effect of statins (time-varying) on CAD and all-cause mortality was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, antihypertensive and antidiabetic medication (all time-varying). Furthermore, we used inverse probability for treatment weighting (IPTW) to account for differences between statin-treated and untreated patients regarding history of CAD before follow-up, age at start of follow-up and age of screening, as well as body mass index, LDL-C and triglycerides. Results: Of the 25,479 identified heFH patients, 11,021 gave informed consent to obtain their medical records, of whom 2,447 could be retrieved. We excluded 766 patients younger than 18. The remaining 1,681 heFH patients comprised our study population and these had very similar characteristics as compared to the 23,798 excluded FH patients, e.g. mean (SD) LDL-C levels were 214 (74) vs. 203 (77) mg/dL. Among 1,151 statin users, there were 133 CAD events and 15 deaths during 10,115 statin treated person-years, compared to 17 CAD events and 9 deaths during 4,965 person-years in 530 never statin users (combined rate: 14.6 vs. 5.2, respectively, p<0.001). After applying IPTW to account for indication bias and correcting for use of other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.61 (0.40 - 0.93). Conclusions: In heFH patients, statins lower the risk for CAD and mortality by 39%.

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.

scholarly journals Lipid Goal Attainment and Prescription Behavior in Asian Patients with Acute Coronary Syndromes: Experience from a Tertiary Hospital

2013 ◽  
Vol 7 ◽  
pp. CMC.S11488 ◽  
Author(s):  
Calvin W Chin ◽  
F Gao ◽  
TT Le ◽  
RS Tan
Keyword(s):  
Goal Attainment ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Dose Titration ◽  
Lipid Lowering Therapy ◽  
Coronary Syndrome ◽  
Asian Patients ◽  
Statin Dose ◽  
Prescription Behavior

Lipid goal attainment studies in Asian patients with acute coronary syndrome (ACS) are limited. The objectives of this study were to determine low-density lipoprotein cholesterol (LDL-C) goal attainment rate at 4 months, and to examine prescription behavior influencing lipid goal attainment in Asian patients with ACS. A retrospective analysis of 267 patients with ACS was performed. The mean follow-up duration was 41.2 ± 10.7 months. LDL-C goal attainment rate was highest at 4 months (36.7%) but declined progressively throughout follow-up. More than 85% of patients were discharged with equipotent statin dose of 2 (equivalent to simvastatin 20 mg) or less. In patients who did not attain LDL-C goals, the statin dose remained low throughout follow-up because of a lack in responsive dose titration. Aggressive lipid-lowering therapy should be initiated early to improve goal attainment in these high-risk patients.

scholarly journals Is Treatment Inertia Unique to Publicly Funded Healthcare? Insights from the Guidelines Oriented Approach to Lipid lowering (GOAL) Canada Program

2021 ◽  
Vol 4 (7) ◽  
pp. 01-06
Author(s):  
Anatoly Langer
Keyword(s):  
Private Insurance ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Multivariable Model ◽  
Public Insurance ◽  
Similar Treatment ◽  
Lowering Therapy ◽  
Oriented Approach

Background: We compared the use of lipid lowering therapy, low density-lipoprotein cholesterol (LDL-C) levels, and proportion achieving guideline-recommended LDL-C levels in patients with private vs. public insurance coverage for their lipid lowering treatment. Materials and Methods: Guidelines Oriented Approach to Lipid lowering (GOAL) Canada enrolled 2009 patients with cardiovascular disease (CVD) or heterozygous familial hypercholesterolemia (FH) and an LDL-C above the guideline-recommended target of <2.0 mmol/L despite maximally tolerated statin therapy. During two follow-up visits physicians received online reminders of treatment recommendations. Results: Of 2009 patients enrolled (median age 63 years, 42% female), there were 1284 (64%) patients with private and 725 (36%) with public insurance for lipid lowering therapy. Patients with private insurance were younger and less likely to have a history of heart failure or to be on bile acid sequestrants. There was no difference between the groups in their lipid levels or lipid lowering therapy at baseline. During the follow up, there was no difference in the use of ezetimibe; however, the use of PCSK9i was more frequent in patients with private insurance (31.7 % vs. 21%, p<0.0001), the mean LDL-C level was slightly lower (2.11±1.17 vs. 2.31±1.17 mmol/L, p = 0.001), and the proportion of patients achieving the guideline-recommended LDL-C level was greater (54% vs. 45.5%, p = 0.001). After adjustment for other factors in a multivariable model, private insurance was not a significant predictor of achieving the guideline-recommended LDL-C level in a multivariable model. Conclusion: While PCSK9i use was higher in patients with private insurance, the majority of patients with either private or public insurance experienced similar treatment inertia. The cost of non-generic medications does not appear to be the dominant reason for the continued care gap in lipid lowering of high-risk patients.

Sign in / Sign up

Export Citation Format

Share Document