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

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

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

PLoS ONE ◽

10.1371/journal.pone.0255345 ◽

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.

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Impact of Lipoprotein(a)-Cholesterol on Accurate Classification of Familial Hypercholesterolemia

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa137.004 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S3-S3

Author(s):

Erica Fatica ◽

Jeffrey W Meeusen ◽

Leslie J Donato

Keyword(s):

Familial Hypercholesterolemia ◽

Density Lipoprotein ◽

Cholesterol Content ◽

Lipid Lowering ◽

Lipoprotein A ◽

Lipid Clinic ◽

Diagnostic Threshold ◽

Before And After ◽

Lipid Testing

Abstract Lipoprotein(a) [Lp(a)] is a pro-atherogenic and pro-thrombotic LDL-like particle recognized as an independent risk factor for cardiovascular disease (CVD) that is resistant to typical lipid-lowering treatments. The cholesterol within Lp(a) (Lp(a)-C) contributes to the reported LDL-cholesterol (LDL-C) concentration by nearly all available methods including beta-quantification, direct homogenous assays, and all estimating equations. Accurate LDL-C measurements are critical for identification of genetic hyperlipidemia conditions such as familial hypercholesterolemia (FH). FH risk estimators such as the Dutch Lipid Clinic Network (DLCN) criteria utilize LDL-C concentration cut-offs and other clinical inputs to assess the likelihood of FH. Therefore, failure to adjust for Lp(a)-C can impact accurate FH classification, appropriate follow-up testing and treatments, and interpretation of cholesterol-lowering treatment efficacy. Lp(a)-C can be estimated from Lp(a) mass as measured by immunoassay using an average cholesterol content per particle. However, Lp(a)-C size and composition varies significantly within individuals resulting in inaccurate Lp(a)-C estimates. In this study, we use direct Lp(a)-C measurements to assess the potential misclassification of FH risk due to the contribution of Lp(a)-C to LDL-C in patient samples submitted for advanced lipoprotein profiling. A total of 28,200 samples submitted for lipoprotein profiling were included. The profiling included lipid testing in a CDC-certified laboratory on Roche cobas 501 (cholesterol and triglycerides by enzymatic method, high-density lipoprotein cholesterol by MgCl2/dextran sulfate precipitation). LDL-C was measured by beta-quantification, and Lp(a)-C by quantitative lipoprotein electrophoresis (SPIFE Vis Cholesterol, Helena Laboratories). The DLCN LDL-C cut-offs (155, 190, 250, and 330mg/dL) were applied to LDL-C results before and after accounting for Lp(a)-C contribution. Lp(a)-C was detected in 3,728 (13.2%) samples. The median (range) concentrations of Lp(a)-C and LDL-C were 11mg/dL (5-108mg/dL) and 121mg/dL (27-678mg/dL), respectively. Overall, subtracting Lp(a)-C would reclassify 6.5% of all samples into a lower LDL-C category within the DLCN algorithm. Within the LDL-C scoring categories, 7.0% (n=222) of subjects with LDL-C 155-189mg/dL, 5.6% (n=66) of subjects with LDL-C 190-249mg/dL, 5.2% (n=10) of subjects with LDL-C 250-329mg/dL, and 3.4% (n=4) of subjects with LDL-C >330mg/dL would be down-classified after adjusting for Lp(a)-C. Limiting to subjects with measurable Lp(a)-C, reclassification to a lower diagnostic threshold occurred in 47.4% of subjects with LDL-C 155-189mg/dL, 37.5% with LDL-C 190-249mg/dL, 41.6% with LDL-C 250-329mg/dL, and 33.3% with LDL-C >330mg/dL after adjustment. Current guidelines recommend screening for elevated Lp(a) in patients with family history of CVD. Our data show that a high percentage of samples evaluated for advanced lipid testing contain measurable Lp(a)-C that could cause mis-classification in FH prediction algorithms. If labeled high probability of FH, these mis-classifications could trigger inappropriate work-up for suspected FH. As clinical follow-up and therapeutic strategies differ between FH and elevated Lp(a), proper distinction between LDL-C and Lp(a)-C is needed to guide appropriate patient management.

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The impact of statin therapy after surgical or endovascular treatment of cerebral aneurysms

Journal of Neurosurgery ◽

10.3171/2019.3.jns183500 ◽

2020 ◽

Vol 133 (1) ◽

pp. 182-189

Author(s):

Tae-Jin Song ◽

Seung-Hun Oh ◽

Jinkwon Kim

Keyword(s):

Statin Therapy ◽

Coil Embolization ◽

Primary Outcome ◽

Cox Regression ◽

Cerebral Aneurysms ◽

Time Dependent ◽

Lipid Lowering ◽

Surgical Clipping ◽

The Impact

OBJECTIVECerebral aneurysms represent the most common cause of spontaneous subarachnoid hemorrhage. Statins are lipid-lowering agents that may expert multiple pleiotropic vascular protective effects. The authors hypothesized that statin therapy after coil embolization or surgical clipping of cerebral aneurysms might improve clinical outcomes.METHODSThis was a retrospective cohort study using the National Health Insurance Service–National Sample Cohort Database in Korea. Patients who underwent coil embolization or surgical clipping for cerebral aneurysm between 2002 and 2013 were included. Based on prescription claims, the authors calculated the proportion of days covered (PDC) by statins during follow-up as a marker of statin therapy. The primary outcome was a composite of the development of stroke, myocardial infarction, and all-cause death. Multivariate time-dependent Cox regression analyses were performed.RESULTSA total of 1381 patients who underwent coil embolization (n = 542) or surgical clipping (n = 839) of cerebral aneurysms were included in this study. During the mean (± SD) follow-up period of 3.83 ± 3.35 years, 335 (24.3%) patients experienced the primary outcome. Adjustments were performed for sex, age (as a continuous variable), treatment modality, aneurysm rupture status (ruptured or unruptured aneurysm), hypertension, diabetes mellitus, household income level, and prior history of ischemic stroke or intracerebral hemorrhage as time-independent variables and statin therapy during follow-up as a time-dependent variable. Consistent statin therapy (PDC > 80%) was significantly associated with a lower risk of the primary outcome (adjusted hazard ratio 0.34, 95% CI 0.14–0.85).CONCLUSIONSConsistent statin therapy was significantly associated with better prognosis after coil embolization or surgical clipping of cerebral aneurysms.

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The Impact of Changes in Population LDL-C Levels on LDL-C Control in Patients After PCI in China: A Retrospective Cohort Study

10.21203/rs.3.rs-101538/v1 ◽

2020 ◽

Author(s):

Huan Liu ◽

Zhipeng Zhou ◽

Yanqing Wu ◽

Jingsong Xu

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Blood Lipid ◽

Coronary Intervention ◽

Lifestyle Changes ◽

Treatment Goal ◽

Lipid Lowering ◽

Lipid Control ◽

The Impact

Abstract BANKGROUND: Mortality from coronary artery disease continues to rise, and secondary prevention and treatment are particularly important. OBJECTIVE: The objective of this study is to evaluate low-density lipoprotein cholesterol (LDL-C) levels in patients after percutaneous coronary intervention (PCI), to describe how treatment outcomes for individual patients changed over time and to examine the potential impact of lipid control rates through population LDL-C levels changes.METHODS: This retrospective study was conducted in patients who underwent PCI between July 2017 and June 2019. The main results included LDL-C levels after PCI. To assess the outcome of prevention, three separate measures of LDL-C were considered: baseline, first follow-up, and final follow-up, and LDL-C control rates were analyzed according to different guidelines. we examine the impact of 0.1mmol/l decreases or increases in population LDL-C levels on LDL-C control.RESULTS: Data were analyzed for 423 patients (mean age, 62 ±10 years), and the baseline LDL-C level was 3.11 ± 0.99 mmol/l. 51.5% of the patients achieved the Chinese Lipids Guidelines treatment goal, 22% and 11.6% of the patients achieved the 2016 ESC Lipids Guidelines and 2019 ESC Lipids Guidelines treatment goal at the final follow-up period respectively. LDL-C levels fluctuated during the follow-up period, and the long-term maintenance results could not be guaranteed after PCI. Population LDL-C levels changes in lifestyle could have a very large impact on LDL-C control in China.CONCLUSION: LDL-C control with statins is not ideal in patients after PCI, which is far from the requirements of the latest guidelines. Although clinicians understand the lipid-lowering effect of statins, they should not give up active lifestyle changes, and should strengthen the comprehensive management of blood lipid control.

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

Circulation ◽

10.1161/circ.132.suppl_3.18995 ◽

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%.

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Improvement in left ventricular mechanics following medical treatment of constrictive pericarditis

Heart ◽

10.1136/heartjnl-2020-317304 ◽

2021 ◽

pp. heartjnl-2020-317304

Author(s):

Kimi Sato ◽

Ayman Ayache ◽

Arnav Kumar ◽

Paul C Cremer ◽

Brian Griffin ◽

...

Keyword(s):

Constrictive Pericarditis ◽

Clinical Symptoms ◽

Heart Association ◽

Left Ventricular ◽

Doppler Imaging ◽

Clinical Resolution ◽

Ventricular Mechanics ◽

Anti Inflammatory ◽

The Impact

ObjectivePatients with constrictive pericarditis (CP) with active inflammation may show resolution with anti-inflammatory therapy. We aimed to investigate the impact of anti-inflammatory medications on constrictive pathophysiology using echocardiography in patients with CP.MethodsWe identified 35 patients with CP who were treated with anti-inflammatory medications (colchicine, prednisone, non-steroidal anti-inflammatory drugs) after diagnosis of CP (mean age 58±13; 80% male). Clinical resolution of CP (transient CP) was defined as improvement in New York Heart Association class during follow-up. We assessed constrictive pathophysiology using regional myocardial mechanics by the ratio of peak early diastolic tissue velocity (e’) at the lateral and septal mitral annulus by tissue Doppler imaging (lateral/septal e’) or the ratio of the left ventricular lateral and septal wall longitudinal strain (LSlateral/LSseptal) by two-dimensional speckle-tracking echocardiography. Longitudinal data were analysed using a mixed effects model.ResultsDuring a median follow-up of 323 days, 20 patients had transient CP, whereas 15 patients had persistent CP. Transient CP had higher baseline erythrocyte sedimentation rates (ESR) (p=0.003) compared with persistent CP. There were no significant differences in LSlateral/LSseptal and lateral/septal e’. During follow-up, only transient CP showed improvement in lateral/septal e’ (p<0.001) and LSlateral/LSseptal (p=0.003), and recovery of inflammatory markers was similar between the two groups. In the logistic model, higher baseline ESR and greater improvement in lateral/septal e’ and LSlateral/LSseptal were associated with clinical resolution of CP using anti-inflammatory therapy.ConclusionsImprovement of constrictive physiology detected by lateral/septal e’ and LSlateral/LSseptal was associated with resolution of clinical symptoms after anti-inflammatory treatment. Serial monitoring of these markers could be used to identify transient CP.

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Prognostic impact of cascade screening for familial hypercholesterolemia on cardiovascular events

European Heart Journal ◽

10.1093/ehjci/ehaa946.2983 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H Tada ◽

H Okada ◽

A Nomura ◽

A Nohara ◽

M Yamagishi ◽

...

Keyword(s):

Risk Factors ◽

Familial Hypercholesterolemia ◽

Cardiovascular Events ◽

Lipid Lowering ◽

Funding Source ◽

Atherosclerotic Cardiovascular Disease ◽

Prognostic Impact ◽

Cascade Screening ◽

Ascvd Risk ◽

The Impact

Abstract Background Early diagnosis and timely treatment for the patients with familial hypercholesterolemia (FH) can substantially lower the risk of atherosclerotic cardiovascular disease (ASCVD). In this sense, cascade screening could be one of the most useful options. However, few data exist regarding the impact of cascade screening for FH on the reduction of risk of ASCVD events. Objectives We aimed to evaluate the prognostic impact of cascade screening for FH. Methods We retrospectively investigated the health records of 1,050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiovascular events (MACE). The median period of follow-up was 12.3 years (interquartile range [IQR] = 9.1–17.5 years), and MACE included death from any causes or hospitalization due to ASCVD events. Results During the observation period, 246 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P<0.001), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.36; 95% CI = 0.22 to 0.60; P<0.001) when compared with the probands, even after adjusting for those known risk factors. Conclusions The identification of patients with FH via cascade screening appeared to result in better prognoses. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Scientific research grants from the Ministry of Education, Science and Culture of Japan (no. 16K19394, 18K08064, and 19K08575)

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CMR analysis of the cardioprotective effects of chronic statin therapy prior to first STEMI: a propensity score analysis

European Heart Journal ◽

10.1093/eurheartj/ehab724.1461 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

G Mendieta Badimon ◽

M Calvo ◽

J Guzman ◽

P Perez ◽

M Alamar ◽

...

Keyword(s):

Propensity Score ◽

Propensity Score Analysis ◽

Smoking Status ◽

Statin Treatment ◽

Left Ventricular ◽

Prior Treatment ◽

Lipid Lowering ◽

Cardioprotective Effects ◽

The Impact

Abstract Background In addition to their lipid-lowering properties, statins possess cardioprotective effects. However, the impact of the latter on acute cardioprotection and adverse left ventricular (LV) remodelling following ST-elevation myocardial infarction (STEMI) have not been investigated through cardiac magnetic resonance (CMR) analysis to date. Purpose To investigate the cardioprotective effects of chronic oral statin treatment prior to first STEMI. Methods The study included 1236 patients with a first STEMI and a CMR performed during the index admission. Among them, 923 underwent a second CMR at 6 months follow-up. The effects of chronic oral statin treatment prior to STEMI on acute infarct size (IS) as a percentage of LV mass, LV ejection fraction (LVEF), microvascular obstruction (MVO), and changes in LV end-diastolic volume (EDVi) and end-systolic volume indexes (ESVi)] at 6 months were evaluated. A propensity score to receive treatment prior to STEMI with statins was calculated based on the inverse probability of treatment weighting (IPTW) from the following parameters: age on admission, sex, smoking status, type 2 diabetes, hypertension, family history of coronary artery disease, current co-treatments (ACEis/ARBs and/or beta-blockers), heart rate (HR), blood pressure (BP) and creatinine levels on admission, and pre-PCI TIMI flow in the culprit artery. Results were stratified according to a symptom-to-balloon time (S2Bt) ≤ or >3 hours. Results The study population's median age was 59 years (IQR 50–68), 16.3% were women; 18.9% were receiving treatment with statins prior to STEMI (table 1). Despite no effect on MVO occurrence (OR: 0.81 [0.60; 1.09], p=0.166), prior treatment with statins was associated with a reduction in IS (18.43% [16.67; 20.19] vs 21.50% [20.67; 22.34], p=0.002), particularly among subjects with ≤3 hours of S2Bt. Accordingly, prior treatment with statins conferred a benefit in mean baseline LVEF (50.23% [48.73; 51.73] vs 48.15% [47.43; 48.87], p=0.014). At 6 months, treatment with statins prior to STEMI blunted the changes in EDVi and ESVi, but only among patients with ≤3 hours of S2Bt (table 2). In addition, a reduction in the probability of adverse LV remodelling, defined as an increase in ESVi >10%, was observed in statin pre-treated patients (OR: 0.67 [0.45; 0.99], p=0.043). Conclusion Treatment with statins before STEMI is associated with improved indexes of cardioprotection as assessed by CMR, particularly among subjects with S2Bt ≤3 hours. Those effects seem to have an impact in limiting adverse LV remodelling as early as 6 months follow-up, and a greater than 10% change in ESVi. These findings warrant further and prospective evaluation of the potential cardioprotective effects of chronic oral statin treatment prior to STEMI. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): This study was partially funded by several grants from Fundaciό La Marato TV3 (2015 30 31 32), Instituto de Salud Carlos III (FIS15/00531) and La Caixa Banking Foundation (HR17-00527).

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Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retrospective survey

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01999-8 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Laura D’Erasmo ◽

Antonio Gallo ◽

Angelo Baldassare Cefalù ◽

Alessia Di Costanzo ◽

Samir Saheb ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Treatment Algorithm ◽

Lipid Lowering ◽

Homozygous Familial Hypercholesterolemia ◽

Lipoprotein Apheresis ◽

Term Efficacy ◽

Threatening Condition ◽

Life Threatening

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Italy (n = 30) and the other with LA in France (n = 29). Results The two cohorts differed significantly for genotype (p = 0.004), baseline lipid profile (p < 0.001), age of treatment initiation (p < 0.001), occurrence of cardiovascular disease (p = 0.003) as well as follow-up duration (p < 0.001). The adjunct of lomitapide to conventional lipid-lowering therapies determined an additional 58.0% reduction of last visit LDL-C levels, compared to 37.1% when LA was added (padj = 0.004). Yearly on-treatment LDL-C < 70 mg/dl and < 55 mg/dl goals were only achieved in 45.5% and 13.5% of HoFH patients treated with lomitapide. The long-term exposure to LDL-C burden was found to be higher in LA than in Lomitapide cohort (13,236.1 ± 5492.1 vs. 11,656.6 ± 4730.9 mg/dL-year respectively, padj = 0.002). A trend towards fewer total cardiovascular events was observed in the Lomitapide than in the LA cohort. Conclusions In comparison with LA, lomitapide appears to provide a better control of LDL-C in HoFH. Further studies are needed to confirm this data and establish whether this translates into a reduction of cardiovascular risk.

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