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8 results on '"Harada-Shiba, Mariko"'

1. Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial

Author

Blom, Dirk J., Harada-Shiba, Mariko, Rubba, Paolo, Gaudet, Daniel, Kastelein, John J. P., Charng, Min-Ji, Pordy, Robert, Donahue, Stephen, Ali, Shazia, Dong, Yuping, Khilla, Nagwa, Banerjee, Poulabi, Baccara-Dinet, Marie, Rosenson, Robert S., ACS - Atherosclerosis & ischemic syndromes, Vascular Medicine, and ACS - Pulmonary hypertension & thrombosis

Subjects
low-density lipoprotein, lipoprotein(a), proprotein convertase subtilisin/kexin type 9 inhibitor, lipids (amino acids, peptides, and proteins), homozygous familial hypercholesterolemia
Abstract

Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by extremely elevated low-density lipoprotein–cholesterol (LDL-C) levels and early onset atherosclerotic cardiovascular disease despite treatment with conventional lipid-lowering treatment. Objectives: This study was designed to assess LDL-C reduction with the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in adult patients with HoFH. Methods: This randomized, double-blind, placebo-controlled, parallel-group, phase 3 study evaluated efficacy and safety of alirocumab 150 mg every 2 weeks. The primary endpoint was percent reduction from baseline in LDL-C versus placebo after 12 weeks of treatment. Results: Patients (N = 69) were randomized 2:1 to alirocumab or placebo. At baseline, background lipid-lowering treatment included 67 patients receiving statin (59 patients on high-intensity statin); 50 patients on ezetimibe; 10 patients on lomitapide; and 10 patients undergoing apheresis. Mean baseline LDL-C was 259.6 mg/dl in the placebo group and 295.0 mg/dl in the alirocumab group. At week 12, the least squares mean difference in LDL-C percent change from baseline was −35.6% (alirocumab [−26.9%] vs. placebo [8.6%]; p < 0.0001). Reductions (least squares mean difference) in other atherogenic lipids at week 12 were: apolipoprotein B, −29.8%; non–high-density lipoprotein cholesterol, −32.9%; total cholesterol, −26.5%; and lipoprotein(a), −28.4% (all p < 0.0001). No serious adverse events, permanent treatment discontinuations, or deaths due to treatment-emergent adverse events were reported during the double-blind treatment period. Conclusions: In the largest randomized controlled interventional trial in HoFH patients to date, alirocumab resulted in significant and clinically meaningful reductions in LDL-C at week 12. Alirocumab was generally well tolerated, with a safety profile comparable to that of placebo. (Study in Participants With Homozygous Familial Hypercholesterolemia [HoFH] [ODYSSEY HoFH] NCT03156621.)

Published
2020

2. Autosomal Recessive Hypercholesterolemia Long-Term Cardiovascular Outcomes

Author

D'Erasmo, Laura, Minicocci, Ilenia, Nicolucci, Antonio, Pintus, Paolo, Roeters Van Lennep, Janine E., Masana, Luis, Mata, Pedro, Sánchez-Hernández, Rosa Maria, Prieto-Matos, Pablo, Real, Josè T., Ascaso, Juan F., Lafuente, Eduardo Esteve, Pocovi, Miguel, Fuentes, Francisco J., Muntoni, Sandro, Bertolini, Stefano, Sirtori, Cesare, Calabresi, Laura, Pavanello, Chiara, Averna, Maurizio, Cefalu, Angelo Baldassare, Noto, Davide, Pacifico, Adolfo Arturo, Pes, Giovanni Mario, Harada-Shiba, Mariko, Manzato, Enzo, Zambon, Sabina, Zambon, Alberto, Vogt, Anja, Scardapane, Marco, Sjouke, Barbara, Fellin, Renato, Arca, Marcello, Internal Medicine, D'Erasmo, Laura, Minicocci, Ilenia, Nicolucci, Antonio, Pintus, Paolo, Roeters Van Lennep, Janine E., Masana, Lui, Mata, Pedro, Sánchez-Hernández, Rosa Maria, Prieto-Matos, Pablo, Real, Josè T., Ascaso, Juan F., Lafuente, Eduardo Esteve, Pocovi, Miguel, Fuentes, Francisco J., Muntoni, Sandro, Bertolini, Stefano, Sirtori, Cesare, Calabresi, Laura, Pavanello, Chiara, Averna, Maurizio, Cefalu, Angelo Baldassare, Noto, Davide, Pacifico, Adolfo Arturo, Pes, Giovanni Mario, Harada-Shiba, Mariko, Manzato, Enzo, Zambon, Sabina, Zambon, Alberto, Vogt, Anja, Scardapane, Marco, Sjouke, Barbara, Fellin, Renato, Arca, Marcello, Graduate School, and Vascular Medicine

Subjects
Adult, Male, Time Factors, Settore MED/09 - Medicina Interna, Adolescent, atherosclerotic cardiovascular disease, autosomal recessive hypercholesterolemia, follow-up, lipid-lowering therapies, retrospective analysis, Hypercholesterolemia, retrospective analysi, Cardiology and Cardiovascular Medicine, Cohort Studies, Young Adult, Humans, Longitudinal Studies, Child, Aged, Retrospective Studies, lipid-lowering therapie, Cholesterol, LDL, Middle Aged, Treatment Outcome, Cardiovascular Diseases, Child, Preschool, Female, Follow-Up Studies
Abstract

BACKGROUND Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. OBJECTIVES Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. METHODS Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. RESULTS We collected data for 52 patients (28 females, 24 males; 31.1 +/- 17.1 years of age; baseline LDL-C: 571.9 +/- 171.7 mg/dl). During a mean follow-up of 14.1 +/- 7.3 years, there was a significant increase in the use of high-intensity statin and ezetimibe in combination with lipoprotein apheresis; in 6 patients, lomitapide was also added. Mean LDL-C achieved at nadir was 164.0 +/- 85.1 mg/dl (similar to 69.6% from baseline), with a better response in patients taking lomitapide (+/- 88.3%). Overall, 23.1% of ARH patients reached LDL-C of = 30 years) and the presence of coronary artery disease at diagnosis were the major predictors of incident ASCVD. CONCLUSIONS Despite intensive treatment, LDL-C in ARH patients remains far from targets, and this translates into a poor long-term cardiovascular prognosis. Our data highlight the importance of an early diagnosis and treatment and confirm the fact that an effective treatment protocol for ARH is still lacking. (c) 2018 by the American College of Cardiology Foundation

Published
2018

3. Multimodality assessment of left ventricular dysfunction in Takayasu arteritis and familial hypercholesterolaemia

Author

Okada, Atsushi, Takahama, Hiroyuki, Ogura, Masatsune, Morita, Yoshiaki, Konma, Junichi, Yoshida, Shuzo, Makino, Shigeki, Takashio, Seiji, Amaki, Makoto, Ohara, Takahiro, Hasegawa, Takuya, Sugano, Yasuo, Kanzaki, Hideaki, Harada‐Shiba, Mariko, Ishibashi‐Ueda, Hatsue, Yasuda, Satoshi, Hanafusa, Toshiaki, and Anzai, Toshihisa

Subjects
Dilated cardiomyopathy, Case Report, cardiovascular diseases, Case Reports, Familial hypercholesterolaemia, Vascular inflammation, Takayasu arteritis
Abstract

Although left ventricular (LV) systolic dysfunction in patients suffering from Takayasu arteritis (TA) has been reported, little is known regarding the development of heart failure in these patients. We report a novel finding of active TA and familial hypercholesterolaemia presenting with severe LV dysfunction through multimodality assessments of LV systolic dysfunction.

Published
2017

4. Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author

Vallejo-Vaz, Antonio J., Marco, Martina De, Stevens, Christophe A. T., Akram, Asif, Freiberger, Tomas, Hovingh, G. Kees, Kastelein, John J. P., Mata, Pedro, Raal, Frederick J., Santos, Raul D., Soran, Handrean, Watts, Gerald F., Abifadel, Marianne, Aguilar-Salinas, Carlos A., Al-Khnifsawi, Mutaz, Alkindi, Fahad A., Alnouri, Fahad, Alonso, Rodrigo, Al-Rasadi, Khalid, Al-Sarraf, Ahmad, Ashavaid, Tester F., Binder, Christoph J., Bogsrud, Martin P., Bourbon, Mafalda, Bruckert, Eric, Chlebus, Krzysztof, Corral, Pablo, Descamps, Olivier, Durst, Ronen, Ezhov, Marat, Fras, Zlatko, Genest, Jacques, Groselj, Urh, Harada-Shiba, Mariko, Kayikcioglu, Meral, Lalic, Katarina, Lam, Carolyn S. P., Latkovskis, Gustavs, Laufs, Ulrich, Liberopoulos, Evangelos, Lin, Jie, Maher, Vincent, Majano, Nelson, Marais, A. David, März, Winfried, Mirrakhimov, Erkin, Miserez, André R., Mitchenko, Olena, Nawawi, Hapizah M., Nordestgaard, B. rge G., Paragh, György, Petrulioniene, Zaneta, Pojskic, Belma, Postadzhiyan, Arman, Reda, Ashraf, Reiner, Željko, Sadoh, Wilson E., Sahebkar, Amirhossein, Shehab, Abdullah, Shek, Aleksander B., Stoll, Mario, Su, Ta-Chen, Subramaniam, Tavintharan, Susekov, Andrey V., Symeonides, Phivos, Tilney, Myra, Tomlinson, Brian, Truong, Thanh-Huong, Tselepis, Alexandros D., Tybjærg-Hansen, Anne, Vázquez-Cárdenas, Alejandra, Viigimaa, Margus, Vohnout, Branislav, Widén, Elisabeth, Yamashita, Shizuya, Banach, Maciej, Gaita, Dan, Jiang, Lixin, Nilsson, Lennart, Santos, Lourdes E., Schunkert, Heribert, Tokgözoğlu, Lale, Car, Josip, Catapano, Alberico L., Ray, Kausik K., Schreier, Laura, Pang, Jing, Dieplinger, Hans, Hanauer-Mader, Gabriele, Desutter, Johan, Langlois, Michel, Mertens, Ann, Rietzschel, Ernst, Wallemacq, Caroline, Isakovic, Dzenana, Dzankovic, Amra M., Obralija, Jasna, Pojskic, Lamija, Sisic, Ibrahim, Stimjanin, Ena, Torlak, Vildana A., Jannes, Cinthia E., Krieger, Jose E., Pereira, Alexandre C., Ruel, Isabelle, Asenjo, Sylvia, Cuevas, Ada, Pećin, Ivan, Miltiadous, George, Panayiotou, Andrie G., Vrablik, Michal, Benn, Marianne, Heinsar, Silver, Béliard, S., Gouni-Berthold, Ioanna, Hengstenberg, Wibke, Julius, Ulrich, Kassner, Ursula, Klose, Gerald, König, Christel, König, Wolfgang, Otte, Britta, Parhofer, Klaus, Schatz, Ulrike, Schmidt, Nina, Steinhagen-Thiessen, Elisabeth, Vogt, Anja, Antza, Christina, Athyros, Vasilios, Bilianou, Eleni, Boufidou, Amalia, Chrousos, George, Elisaf, Moses, Garoufi, Anastasia, Katsiki, Niki, Kolovou, Genovefa, Kotsis, Vasilios, Rallidis, Loukianos, Rizos, Christos, Skalidis, Emmanouel, Skoumas, Ioannis, Tziomalos, Kostantinos, Shawney, J. P. S., Abbaszadegan, Mohammad R., Aminzadeh, Majid, Hosseini, Sousan, Mobini, Moein, Vakili, Rahim, Zaeri, Hossein, Agar, Ruth, Boran, Gerard, Colwell, Nial, Crowley, Vivion, Durkin, Maeve, Griffin, Damian, Kelly, Michael, Rakovac-Tisdall, Ana, Bitzur, Rafael, Cohen, Hofit, Eliav, Osnat, Ellis, Avishay, Gavish, Dov, Harats, Dror, Henkin, Yaacov, Knobler, Hila, Leavit, Leah, Leitersdorf, Eran, Rubinstein, Ardon, Schurr, Daniel, Shpitzen, Shoshi, Szalat, Auryan, Arca, Marcello, Averna, Maurizio, Bertolini, Stefano, Calandra, Sebastiano, Tarugi, Patrizia, Erglis, Andrejs, Gilis, Dainus, Nesterovics, Georgijs, Saripo, Vita, Upena-Roze, Arta, Elbitar, Sandy, Jambart, S. lim, Khoury, Petra El, Gargalskaite, Urte, Kutkiene, Sandra, Al-Khateeb, Alyaa, An, Chua Y., Ismail, Zaliha, Kasim, Sazzli, Ibrahim, Khairul S., Radzi, Ahmad B. M., Kasim, Noor A., Nor, Noor S. M., Ramli, Anis S., Razak, Suraya A., Muid, Suhaila, Rosman, Azhari, Sanusi, Abd R., Razman, Aimi Z., Nazli, Sukma A., Kek, Teh L., Azzopardi, Conrad, Aguilar Salinas, Carlos A., Vázquez-Cárdenas, N. Alejandra, Galán, Gabriela, Magaña-Torres, M. T., Martagon, Alexandro, Mehta, Roopa, Wittekoek, M. E., Isara, Alphonsus R., Obaseki, Darlington E., Ohenhen, Oluwatoyin A., Holven, Kirsten B., Gruchała, Marcin, Baranowska, Marlena, Borowiec-Wolny, Justyna, Gilis-Malinowska, Natasza, Michalska-Grzonkowska, Aleksandra, Pajkowski, Marcin, Parczewska, Aleksandra, Romanowska-Kocejko, Marzena, Stróżyk, Aneta, Żarczyńska-Buchowiecka, Marta, Kleinschmidt, Mariola, Alves, Ana C., Medeiros, Ana M., Ershova, Alexandra, Korneva, Victoria, Kuznetsova, Tatiana, Malyshev, Pavel, Meshkov, Alexey, Rozhkova, Tatiana, Rajkovic, Natasa, Popovic, Ljiljana, Lukac, Sandra S., Stosic, Ljubica, Rasulic, Iva, Lalic, Nebojsa M., Chua, Terrance S. J., Ting, Sharon P. L., Raslova, Katarina, Battelino, Tadej, Cevc, Matija, Jug, Borut, Kovac, Jernej, Podkrajsek, Katarina T., Sustar, Ursa, Trontelj, Katja J., Marais, David, Isla, Leopoldo Perez de, Martin, François J., Charng, Ming-Ji, Chen, Pei-Lung, Kayikçioglu, Meral, Dell’oca, Nicolás, Fernández, Graciela, Ressia, Andrés, Reyes, Ximena, Zelarayan, Mario, Alieva, Rano B., Hoshimov, Shavkat U., Kurbanov, Ravshanbek D., Nizamov, Ulugbek I., Lima-Martínez, Marcos M., Nguyen, Mai-Ngoc Thi, Do, Doan-Loi, Kim, Ngoc-Thanh, le, Hong-An, le, Thanh-Tung, Centre of Excellence in Complex Disease Genetics, Elisabeth Ingrid Maria Widen / Principal Investigator, Institute for Molecular Medicine Finland, University of Helsinki, Genomic Discoveries and Clinical Translation, Kardiyoloji, Lee Kong Chian School of Medicine (LKCMedicine), Pfizer Incorporated, European Atherosclerosis Society, ACS - Atherosclerosis & ischemic syndromes, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and Ege Üniversitesi

Subjects
International Cooperation, MÉTODOS EPIDEMIOLÓGICOS, 030204 cardiovascular system & hematology, Nationwide survey, Global Health, Health Services Accessibility, Doenças Cardio e Cérebro-vasculares, MOLECULAR-GENETICS, 0302 clinical medicine, Risk Factors, Prevalence, CARDIOVASCULAR RISK-FACTORS, 030212 general & internal medicine, Cooperative Behavior, DEFECTIVE APOLIPOPROTEIN B-100, GENERAL-POPULATION, education.field_of_study, medicine.diagnostic_test, Anticholesteremic Agents, Familial hypercholesterolaemia, FHSC, Primary dyslipidaemia, Biomarkers, Cholesterol, LDL, Genetic Predisposition to Disease, Health Care Surveys, Healthcare Disparities, Humans, Hyperlipoproteinemia Type II, Phenotype, Predictive Value of Tests, Treatment Outcome, Blood Component Removal, EAS Familial Hypercholesterolaemia Studies Collaboration, 3. Good health, PREVALENCE, Cholesterol, CORONARY-ARTERY-DISEASE, NATIONWIDE SURVEY, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Cardiovascular risk factors, Population, LDL-RECEPTOR, 1102 Cardiovascular Medicine And Haematology, LDL, 03 medical and health sciences, medicine, Medicine [Science], fhsc, familial hypercholesterolaemia, primary dyslipidaemia, education, Genetic testing, Government, Public health, EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC) Investigators, SAFEHEART REGISTRY, 1103 Clinical Sciences, Cardiovascular System & Hematology, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Cardiovascular System & Cardiology, Business, FOLLOW-UP
Abstract

PubMed: 30270054, 2-s2.0-85053666909, Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ?2/3 countries. Lipoprotein-apheresis is offered in ?60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed. © 2018 Elsevier B.V., Universidade de São Paulo, USP European Atherosclerosis Society, EAS Amgen Merck Sharp and Dohme, MSD, The ELSA Study suggests heterozygous FH (HeFH) may affect 1:263 Brazilians (?766,000 individuals). Currently, the only active genetic cascade screening program in Brazil is Hipercol Brasil in Sao Paulo (genetic testing for adults with low-density lipoprotein cholesterol (LDL-C) ?230?mg/dL, to maximise cost-effectiveness), with 1719 heterozygotes, 25 homozygotes, 13 compound-heterozygotes and one double-heterozygote identified by March 2018. To date, 4340 individuals from 440 families were screened. Genetic testing is funded by a government tax reduction programme (PROADI-SUS), and cascade screening by partnering between Samaritano Hospital and Heart Institute (InCor) University of Sao Paulo. Most FH patients are under non-specialist care and currently under-treated., Prevalence is unknown but assumed at 1:250. There is no state programme and few patients were diagnosed before the Latvian FH Registry was established in 2015. To date, the Registry has identified 181 cases (2.3% of 7876 estimated HeFH cases; no HoFH). Cascade screening is performed in first-degree relatives of index cases with probable/definite FH. Genetic testing is not reimbursed but has been funded by research grants for a few patients/relatives. About 5% of patients had LDL-C at target before inclusion in the Registry [ 61 ]. Statins are reimbursed 50% in primary prevention; statins and ezetimibe, 75–100% in secondary prevention; PCSK9i are available, but not reimbursed., Estimated prevalence is 1:250 (based on a meta-analysis of 6 observational studies) or 136,300 adults (only 2% diagnosed) [ 69 , 70 ]. Based on LIPIDOGRAM studies (2004–2015, ?50,000 participants), prevalence might be?1:200 [ 71 , 72 ]. Five HoFH cases are described [ 73 , 74 ]. Patients with DLCN ?3 are referred for genetic testing, funded by the National Health Program. The National Centre for FH at University Clinical Hospital, Medical University of Gdansk, was established in 2017, financed by the Ministry of Health. From August 2017, 345 patients underwent genetic testing (153 positive, including 46 relatives; 1 HoFH). Since 1999, 1884 patients (562 families) have undergone genetic testing and cascade diagnosis (data from the National Polish FH Registry, Medical University of Gdansk, established in 2000). PCSK9i are not reimbursed (under discussion with the Ministry of Health)., The EAS FHSC project has received support from a Pfizer Independent Grant for Learning & Change 2014 (No: 16157823 ) and from investigator-initiated unrestricted research grants to the European Atherosclerosis Society from Amgen , MSD , and Sanofi-Aventis .

Published
2018

5. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel

Author

Sturm, Amy C., Knowles, Joshua W., Gidding, Samuel S., Ahmad, Zahid S., Ahmed, Catherine D., Ballantyne, Christie M., Baum, Seth J., Bourbon, Mafalda, Carrié, Alain, Cuchel, Marina, de Ferranti, Sarah D., Defesche, Joep C., Freiberger, Tomas, Hershberger, Ray E., Hovingh, G. Kees, Karayan, Lala, Kastelein, Johannes Jacob Pieter, Kindt, Iris, Lane, Stacey R., Leigh, Sarah E., Linton, MacRae F., Mata, Pedro, Neal, William A., Nordestgaard, Børge G., Santos, Raul D., Harada-Shiba, Mariko, Sijbrands, Eric J., Stitziel, Nathan O., Yamashita, Shizuya, Wilemon, Katherine A., Ledbetter, David H., Rader, Daniel J., and convened by the Familial Hypercholesterolemia Foundation

Subjects
Consensus Statement, Cascade Testing, Genetic Counseling, Genetic Testing, Familial Hypercholesterolemia, Doenças Cardio e Cérebro-vasculares
Abstract

Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification. info:eu-repo/semantics/publishedVersion

Published
2018

6. Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author

Vallejo-Vaz, Antonio J., De Marco, Martina, Stevens, Christophe A.T., Akram, Asif, Freiberger, Tomas, Hovingh, G. Kees, Kastelein, John J.P., Mata, Pedro, Raal, Frederick J., Santos, Raul D., Soran, Handrean, Watts, Gerald F., Abifadel, Marianne, Aguilar-Salinas, Carlos A., Al- khnifsawi, Mutaz, AlKindi, Fahad A., Alnouri, Fahad, Alonso, Rodrigo, Al-Rasadi, Khalid, Al-Sarraf, Ahmad, Ashavaid, Tester F., Binder, Christoph J., Bogsrud, Martin P., Bourbon, Mafalda, Bruckert, Eric, Chlebus, Krzysztof, Corral, Pablo, Descamps, Olivier, Durst, Ronen, Ezhov, Marat, Fras, Zlatko, Genest, Jacques, Groselj, Urh, Harada-Shiba, Mariko, Kayikcioglu, Meral, Lalic, Katarina, Lam, Carolyn S.P., Latkovskis, Gustavs, Laufs, Ulrich, Liberopoulos, Evangelos, Lin, Jie, Maher, Vincent, Majano, Nelson, Marais, A. David, März, Winfried, Mirrakhimov, Erkin, Miserez, André R., Mitchenko, Olena, Nawawi, Hapizah M., Nordestgaard, Børge G., Paragh, György, Petrulioniene, Zaneta, Pojskic, Belma, Postadzhiyan, Arman, Reda, Ashraf, Reiner, Željko, Sadoh, Wilson E., Sahebkar, Amirhossein, Shehab, Abdullah, Shek, Aleksander B., Stoll, Mario, Su, Ta- Chen, Subramaniam, Tavintharan, Susekov, Andrey V., Symeonides, Phivos, Tilney, Myra, Tomlinson, Brian, Truong, Thanh-Huong, Tselepis, Alexandros D., Tybjærg-Hansen, Anne, Vázquez-Cárdenas, Alejandra, Viigimaa, Margus, Vohnout, Branislav, Widén, Elisabeth, Yamashita, Shizuya, Banach, Maciej, Gaita, Dan, Jiang, Lixin, Nilsson, Lennart, Santos, Lourdes E., Schunkert, Heribert, Tokgözoğlu, Lale, Car, Josip, Catapano, Alberico L., and Ray, Kausik K.

Subjects
BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, primary dyslipidaemia, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, familial hypercholesterolaemia, FHSC
Abstract

Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. METHODS: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. RESULTS: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein- apheresis is offered in ∼60% countries, although access is limited. CONCLUSIONS: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under- treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed

Published
2018

7. Worldwide experience of homozygous familial hypercholesterolaemia:retrospective cohort study

Author

Tycho R Tromp, Merel L Hartgers, G Kees Hovingh, Antonio J Vallejo-Vaz, Kausik K Ray, Handrean Soran, Tomas Freiberger, Stefano Bertolini, Mariko Harada-Shiba, Dirk J Blom, Frederick J Raal, Marina Cuchel, Tycho R. Tromp, Merel L. Hartgers, G. Kees Hovingh, Antonio J. Vallejo-Vaz, Kausik K. Ray, Stefano A. Bertolini, Jing Pang, Gerald F. Watts, Susanne Greber-Platzer, Martin Mäser, Thomas M. Stulnig, Christoph F. Ebenbichler, Khalid Bin Thani, David Cassiman, Olivier S. Descamps, Daisy Rymen, Peter Witters, Raul D. Santos, Liam R. Brunham, Gordon A. Francis, Jacques Genest, Robert A. Hegele, Brooke A. Kennedy, Isabelle Ruel, Mark H. Sherman, Long Jiang, Luya Wang, Željko Reiner, Vladimir Blaha, Richard Ceska, Jana Dvorakova, Lubomir Dlouhy, Pavel Horak, Vladimir Soska, Lukas Tichy, Robin Urbanek, Helena Vaverkova, Michal Vrablik, Stanislav Zemek, Lukas Zlatohlavek, Sameh Emil, Tarek Naguib, Ashraf Reda, Sophie Béliard, Eric Bruckert, Antonio Gallo, Moses S. Elisaf, Genovefa Kolovou, Hofit Cohen, Ronen Durst, Eldad J. Dann, Avishay Elis, Osama Hussein, Eran Leitersdorf, Daniel Schurr, Nitika Setia, Ishwar C. Verma, Mohammed D. Alareedh, Mutaz Al-Khnifsawi, Ali F. Abdalsahib Al-Zamili, Sabah H. Rhadi, Foaad K. Shaghee, Marcello Arca, Maurizio Averna, Andrea Bartuli, Marco Bucci, Paola S. Buonuomo, Paolo Calabrò, Sebastiano Calandra, Manuela Casula, Alberico L. Catapano, Angelo B. Cefalù, Arrigo F.G. Cicero, Sergio D'Addato, Laura D'Erasmo, Alessia Di Costanzo, Tommaso Fasano, Marta Gazzotti, Antonina Giammanco, Gabriella Iannuzzo, Anastasia Ibba, Emanuele A. Negri, Andrea Pasta, Chiara Pavanello, Livia Pisciotta, Claudio Rabacchi, Carlo Ripoli, Tiziana Sampietro, Francesco Sbrana, Fulvio Sileo, Patrizia Suppressa, Patrizia Tarugi, Chiara Trenti, Maria G. Zenti, Mika Hori, Mahmoud H. Ayesh, Sami T. Azar, Fadi F. Bitar, Akl C. Fahed, Elie M. Moubarak, Georges Nemer, Hapizah M. Nawawi, Ramón Madriz, Roopa Mehta, Arjen J. Cupido, Joep C. Defesche, M. Doortje Reijman, Jeanine E. Roeters-van Lennep, Erik S.G. Stroes, Albert Wiegman, Linda Zuurbier, Khalid Al-Waili, Fouzia Sadiq, Krzysztof Chlebus, Mafalda Bourbon, Isabel M. Gaspar, Katarina S. Lalic, Marat V. Ezhov, Andrey V. Susekov, Urh Groselj, Min-Ji Charng, Weerapan Khovidhunkit, Melih Aktan, Bulent B. Altunkeser, Sinan Demircioglu, Melis Kose, Cumali Gokce, Osman Ilhan, Meral Kayikcioglu, Leyla G. Kaynar, Irfan Kuku, Erdal Kurtoglu, Harika Okutan, Osman I. Ozcebe, Zafer Pekkolay, Saim Sag, Osman Z. Salcioglu, Ahmet Temizhan, Mustafa Yenercag, Mehmet Yilmaz, Hamiyet Yilmaz Yasar, Olena Mitchenko, Alexander R.M. Lyons, Christophe A.T. Stevens, Julie A. Brothers, Lisa C. Hudgins, Christina Nguyen, Rano Alieva, Aleksandr Shek, Doan-Loi Do, Ngoc-Thanh Kim, Hong-An Le, Thanh-Tung Le, Mai-Ngoc T. Nguyen, Thanh-Huong Truong, Dirk J. Blom, Frederick J. Raal, VU University medical center, Tromp T.R., Hartgers M.L., Hovingh G.K., Vallejo-Vaz A.J., Ray K.K., Soran H., Freiberger T., Bertolini S., Harada-Shiba M., Blom D.J., Raal F.J., Cuchel M., Bertolini S.A., Pang J., Watts G.F., Greber-Platzer S., Maser M., Stulnig T.M., Ebenbichler C.F., Bin Thani K., Cassiman D., Descamps O.S., Rymen D., Witters P., Santos R.D., Brunham L.R., Francis G.A., Genest J., Hegele R.A., Kennedy B.A., Ruel I., Sherman M.H., Jiang L., Wang L., Reiner Z., Blaha V., Ceska R., Dvorakova J., Dlouhy L., Horak P., Soska V., Tichy L., Urbanek R., Vaverkova H., Vrablik M., Zemek S., Zlatohlavek L., Emil S., Naguib T., Reda A., Beliard S., Bruckert E., Gallo A., Elisaf M.S., Kolovou G., Cohen H., Durst R., Dann E.J., Elis A., Hussein O., Leitersdorf E., Schurr D., Setia N., Verma I.C., Alareedh M.D., Al-Khnifsawi M., Abdalsahib Al-Zamili A.F., Rhadi S.H., Shaghee F.K., Arca M., Averna M., Bartuli A., Bucci M., Buonuomo P.S., Calabro P., Calandra S., Casula M., Catapano A.L., Cefalu A.B., Cicero A.F.G., D'Addato S., D'Erasmo L., Di Costanzo A., Fasano T., Gazzotti M., Giammanco A., Iannuzzo G., Ibba A., Negri E.A., Pasta A., Pavanello C., Pisciotta L., Rabacchi C., Ripoli C., Sampietro T., Sbrana F., Sileo F., Suppressa P., Tarugi P., Trenti C., Zenti M.G., Hori M., Ayesh M.H., Azar S.T., Bitar F.F., Fahed A.C., Moubarak E.M., Nemer G., Nawawi H.M., Madriz R., Mehta R., Cupido A.J., Defesche J.C., Reijman M.D., Roeters-van Lennep J.E., Stroes E.S.G., Wiegman A., Zuurbier L., Al-Waili K., Sadiq F., Chlebus K., Bourbon M., Gaspar I.M., Lalic K.S., Ezhov M.V., Susekov A.V., Groselj U., Charng M.-J., Khovidhunkit W., Aktan M., Altunkeser B.B., Demircioglu S., Kose M., Gokce C., Ilhan O., Kayikcioglu M., Kaynar L.G., Kuku I., Kurtoglu E., Okutan H., Ozcebe O.I., Pekkolay Z., Sag S., Salcioglu O.Z., Temizhan A., Yenercag M., Yilmaz M., Yilmaz Yasar H., Mitchenko O., Lyons A.R.M., Stevens C.A.T., Brothers J.A., Hudgins L.C., Nguyen C., Alieva R., Shek A., Do D.-L., Kim N.-T., Le H.-A., Le T.-T., Nguyen M.-N.T., Truong T.-H., University of Amsterdam, University of Pennsylvania, European Atherosclerosis Society, Experimental Vascular Medicine, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Human Genetics, Paediatric Metabolic Diseases, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Heart failure & arrhythmias, R Tromp, Tycho, L Hartgers, Merel, Kees Hovingh, G, J Vallejo-Vaz, Antonio, K Ray, Kausik, Soran, Handrean, Freiberger, Toma, A Bertolini, Stefano, Harada-Shiba, Mariko, Pang, Jing, F Watts, Gerald, Greber-Platzer, Susanne, Mäser, Martin, M Stulnig, Thoma, F Ebenbichler, Christoph, Bin Thani, Khalid, Cassiman, David, S Descamps, Olivier, Rymen, Daisy, Witters, Peter, D Santos, Raul, R Brunham, Liam, A Francis, Gordon, Genest, Jacque, A Hegele, Robert, A Kennedy, Brooke, Ruel, Isabelle, H Sherman, Mark, Jiang, Long, Wang, Luya, Reiner, Željko, Blaha, Vladimir, Ceska, Richard, Dvorakova, Jana, Dlouhy, Lubomir, Horak, Pavel, Soska, Vladimir, Tichy, Luka, Urbanek, Robin, Vaverkova, Helena, Vrablik, Michal, Zemek, Stanislav, Zlatohlavek, Luka, Emil, Sameh, Naguib, Tarek, Reda, Ashraf, Béliard, Sophie, Bruckert, Eric, Gallo, Antonio, S Elisaf, Mose, Kolovou, Genovefa, Cohen, Hofit, Durst, Ronen, J Dann, Eldad, Elis, Avishay, Hussein, Osama, Leitersdorf, Eran, Schurr, Daniel, Setia, Nitika, C Verma, Ishwar, D Alareedh, Mohammed, Al-Khnifsawi, Mutaz, F Abdalsahib Al-Zamili, Ali, H Rhadi, Sabah, K Shaghee, Foaad, Arca, Marcello, Averna, Maurizio, Bartuli, Andrea, Bucci, Marco, S Buonuomo, Paola, Calabrò, Paolo, Calandra, Sebastiano, Casula, Manuela, L Catapano, Alberico, B Cefalù, Angelo, G Cicero, Arrigo F, D'Addato, Sergio, D'Erasmo, Laura, Di Costanzo, Alessia, Fasano, Tommaso, Gazzotti, Marta, Giammanco, Antonina, Iannuzzo, Gabriella, Ibba, Anastasia, A Negri, Emanuele, Pasta, Andrea, Pavanello, Chiara, Pisciotta, Livia, Rabacchi, Claudio, Ripoli, Carlo, Sampietro, Tiziana, Sbrana, Francesco, Sileo, Fulvio, Suppressa, Patrizia, Tarugi, Patrizia, Trenti, Chiara, G Zenti, Maria, Hori, Mika, H Ayesh, Mahmoud, T Azar, Sami, F Bitar, Fadi, C Fahed, Akl, M Moubarak, Elie, Nemer, George, M Nawawi, Hapizah, Madriz, Ramón, Mehta, Roopa, J Cupido, Arjen, C Defesche, Joep, Doortje Reijman, M, E Roeters-van Lennep, Jeanine, G Stroes, Erik S, Wiegman, Albert, Zuurbier, Linda, Al-Waili, Khalid, Sadiq, Fouzia, Chlebus, Krzysztof, Bourbon, Mafalda, M Gaspar, Isabel, S Lalic, Katarina, V Ezhov, Marat, V Susekov, Andrey, Groselj, Urh, Charng, Min-Ji, Khovidhunkit, Weerapan, Aktan, Melih, B Altunkeser, Bulent, Demircioglu, Sinan, Kose, Meli, Gokce, Cumali, Ilhan, Osman, Kayikcioglu, Meral, G Kaynar, Leyla, Kuku, Irfan, Kurtoglu, Erdal, Okutan, Harika, I Ozcebe, Osman, Pekkolay, Zafer, Sag, Saim, Z Salcioglu, Osman, Temizhan, Ahmet, Yenercag, Mustafa, Yilmaz, Mehmet, Yilmaz Yasar, Hamiyet, Mitchenko, Olena, M Lyons, Alexander R, T Stevens, Christophe A, A Brothers, Julie, C Hudgins, Lisa, Nguyen, Christina, Alieva, Rano, Shek, Aleksandr, Do, Doan-Loi, Kim, Ngoc-Thanh, Le, Hong-An, Le, Thanh-Tung, T Nguyen, Mai-Ngoc, Truong, Thanh-Huong, J Blom, Dirk, J Raal, Frederick, and Cuchel, Marina

Subjects
Adult, Male, Homozygous Familial Hypercholesterolemia, Adolescent, retrospective study, CHILDREN, Doenças Cardio e Cérebro-vasculares, Cohort Studies, Young Adult, Medicine, General & Internal, General & Internal Medicine, Cardiovascular Disease, Humans, Registries, LIPOPROTEIN-APHERESIS, Child, 11 Medical and Health Sciences, Retrospective Studies, Homozygous Familial Hypercholesterolaemia International Clinical Collaborators, Science & Technology, GUIDANCE, clinical characteristic, EVOLOCUMAB, Homozygous familial hypercholesterolemia, Worldwide, Therapies, Cardiovascular disease, General Medicine, CARE, OPEN-LABEL, EFFICACY, INSIGHTS, Child, Preschool, outcome, Female, genetic, Familial Hypercholesterolaemia, Life Sciences & Biomedicine
Abstract

[Background]: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally., [Methods]: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005., [Findings]: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12∙0 years (IQR 5∙5–27∙0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14∙7 mmol/L (IQR 11∙6–18∙4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3∙93 mmol/L, IQR 2∙6–5∙8) versus non-highincome countries (9∙3 mmol/L, 6∙7–12∙7), with greater use of three or more lipid-lowering therapies (LLT; highincome 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24∙5 years (IQR 17∙0–34∙5) versus 37∙0 years (29∙0–49∙0) in high-income countries (adjusted hazard ratio 1∙64, 95% CI 1∙13–2∙38)., [Interpretation]: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH., Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Society

Published
2022

8. Evinacumab for Homozygous Familial Hypercholesterolemia

Author

Gerald Watts, Farrah Deeba, David Sullivan, Paul Donald Bonnitcha, San San Min, Nimalie Jacintha Nanayakkara, Christopher Ebenbichler, Alexander Tschoner, Clemens Engler, Daniel Gaudet, Nathalie Roy, David Blackburn, Jean Bergeron, Hisee Villeneuve, Samir Saheb, Antonio Gallo, Sophia Beliard, Bertrand Dussol, Sophie Morange, Pascale Poullin, Rene Valero, Charalampos Milionis, Sebastian Filippas-Ntekouan, Eleftherios Klouras, Genovefa Kolovou, George Hatzigeorgiou, Spyridon Rammos, Paolo Rubba, Gabriella Iannuzzo, Mariko Harada-Shiba, Cheol Son, Hisashi Makino, Kiminori Hosoda, Kota Matsuki, Kyoko Kohmo, Masaki Matsubara, Masatsune Ogura, Michio Noguchio, Miki Matsuo, Ryo Koezuka, Tamiko Tamanaha, Tsutomu Tomita, Yoko Ohata, Yoshihiko Otsubo, Noriaki Koyanagi, Masaaki Kawashiri, Hayato Tada, Atsushi Nohara, Akihiro Nomura, Hirofumi Okada, Naohiko Fujii, Daisuke Hayashi, Sayoko Yonemoto, Shungo Fukuda, Koji Yanagi, Miwa Ryo, Masahiro Koseki, Makoto Nishida, Takeshi Okada, Erik Stroes, Laurens Reeskamp, Daniela Stols-Goncalves, Eva Hamulyak, Anho H Liem, Jurgen M Akkerhuis, Pieter R Nierop, Bastiaan M van Dalen, Sweder W E van de Poll, Adriana J M van Miltenburg-van Zijl, Marinus J Veerhoek, Frederick Raal, Sindeep Amrat Bhana, Olena Mitchenko, Vadym Romanov, Iryna Chulaevska, Leonid Rudenko, Olena Beregova, Igor Vakaliuk, Iryna Drapchak, Natalia Tymochko, Anna Isayeva, Olena Buriakovska, Maryna Vovchenko, Vira Tseluyko, Nataliya Matviychuk, Larysa Yakovleva, Paul Duell, Jonathan Barton Purnell, Robert Rosenson, Donald Smith, Theresa Halloran, Robert Gottlieb, Peter A McCullough, Zachary P Rosol, Andy Y Lee, Clay M Barbin, Seth J Baum, Reina Mendelson, Melissa Wright, Linda Hemphill, Akl Fahed, Traci Turner, Angela Ellard, Gerald Watts, ., Deeba, Farrah, Sullivan, David, Donald Bonnitcha, Paul, San Min, San, Jacintha Nanayakkara, Nimalie, Ebenbichler, Christopher, Tschoner, Alexander, Engler, Clemen, Gaudet, Daniel, Roy, Nathalie, Blackburn, David, Bergeron, Jean, Villeneuve, Hisee, Saheb, Samir, Gallo, Antonio, Beliard, Sophia, Dussol, Bertrand, Morange, Sophie, Poullin, Pascale, Valero, Rene, Milionis, Charalampo, Filippas-Ntekouan, Sebastian, Klouras, Eleftherio, Kolovou, Genovefa, Hatzigeorgiou, George, Rammos, Spyridon, Rubba, PAOLO OSVALDO FEDERICO, Iannuzzo, Gabriella, Harada-Shiba, Mariko, Son, Cheol, Makino, Hisashi, Hosoda, Kiminori, Matsuki, Kota, Kohmo, Kyoko, Matsubara, Masaki, Ogura, Masatsune, Noguchio, Michio, Matsuo, Miki, Koezuka, Ryo, Tamanaha, Tamiko, Tomita, Tsutomu, Ohata, Yoko, Otsubo, Yoshihiko, Koyanagi, Noriaki, Kawashiri, Masaaki, Tada, Hayato, Nohara, Atsushi, Nomura, Akihiro, Okada, Hirofumi, Fujii, Naohiko, Hayashi, Daisuke, Yonemoto, Sayoko, Fukuda, Shungo, Yanagi, Koji, Ryo, Miwa, Koseki, Masahiro, Nishida, Makoto, Okada, Takeshi, Stroes, Erik, Reeskamp, Lauren, Stols-Goncalves, Daniela, Hamulyak, Eva, H Liem, Anho, M Akkerhuis, Jurgen, R Nierop, Pieter, M van Dalen, Bastiaan, E van de Poll, Sweder W, M van Miltenburg-van Zijl, Adriana J, J Veerhoek, Marinu, Raal, Frederick, Amrat Bhana, Sindeep, Mitchenko, Olena, Romanov, Vadym, Chulaevska, Iryna, Rudenko, Leonid, Beregova, Olena, Vakaliuk, Igor, Drapchak, Iryna, Tymochko, Natalia, Isayeva, Anna, Buriakovska, Olena, Vovchenko, Maryna, Tseluyko, Vira, Matviychuk, Nataliya, Yakovleva, Larysa, Duell, Paul, Barton Purnell, Jonathan, Rosenson, Robert, Smith, Donald, Halloran, Theresa, Gottlieb, Robert, A McCullough, Peter, P Rosol, Zachary, Y Lee, Andy, M Barbin, Clay, J Baum, Seth, Mendelson, Reina, Wright, Melissa, Hemphill, Linda, Fahed, Akl, Turner, Traci, Ellard, Angela, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Experimental Vascular Medicine, and ACS - Pulmonary hypertension & thrombosis

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Evinacumab, Angiopoietin-like Protein, Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Internal medicine, Anticholesteremic Agent, Medicine, Infusions, Intravenou, 030212 general & internal medicine, Child, Aged, Least-Squares Analysi, business.industry, Cholesterol, Homozygote, Antibodies, Monoclonal, Cholesterol, LDL, General Medicine, Middle Aged, medicine.disease, Endocrinology, Receptors, LDL, Multicenter study, chemistry, Ldl metabolism, Mutation, Female, lipids (amino acids, peptides, and proteins), business, Human, Lipoprotein
Abstract

BACKGROUND: Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS: The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval [CI], -65.0 to -33.1; P

Published
2020

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