Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

none724siBackground The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally.Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases.Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p<0.001).Interpretation Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia. Copyright (C) 2021 Elsevier Ltd. All rights reserved.mixedVallejo-Vaz, Antonio J.; Stevens, Christophe A.T.; Lyons, Alexander R.M.; Dharmayat, Kanika I.; Freiberger, Tomas; Hovingh, G. Kees; Mata, Pedro; Raal, Frederick J.; Santos, Raul D.; Soran, Handrean; Watts, Gerald F.; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alhabib, Khalid F.; Alkhnifsawi, Mutaz; Almahmeed, Wael; Alnouri, Fahad; Alonso, Rodrigo; Al-Rasadi, Khalid; Al-Sarraf, Ahmad; Al-Sayed, Nasreen; Araujo, Francisco; Ashavaid, Tester F.; Banach, Maciej; Béliard, Sophie; Benn, Marianne; Binder, Christoph J.; Bogsrud, Martin P.; Bourbon, Mafalda; Chlebus, Krzysztof; Corral, Pablo; Davletov, Kairat; Descamps, Olivier S.; Durst, Ronen; Ezhov, Marat; Gaita, Dan; Genest, Jacques; Groselj, Urh; Harada-Shiba, Mariko; Holven, Kirsten B.; Kayikcioglu, Meral; Khovidhunkit, Weerapan; Lalic, Katarina; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lima-Martinez, Marcos M.; Lin, Jie; Maher, Vincent; Marais, A. David; März, Winfried; Mirrakhimov, Erkin; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah; Nordestgaard, Børge G.; Panayiotou, Andrie G.; Paragh, György; Petrulioniene, Zaneta; Pojskic, Belma; Postadzhiyan, Arman; Raslova, Katarina; Reda, Ashraf; Reiner, Željko; Sadiq, Fouzia; Sadoh, Wilson Ehidiamen; Schunkert, Heribert; Shek, Aleksandr B.; Stoll, Mario; Stroes, Erik; Su, Ta-Chen; Subramaniam, Tavintharan; Susekov, Andrey V.; Tilney, Myra; Tomlinson, Brian; Truong, Thanh Huong; Tselepis, Alexandros D.; Tybjærg-Hansen, Anne; Vázquez Cárdenas, Alejandra; Viigimaa, Margus; Wang, Luya; Yamashita, Shizuya; Kastelein, John J.P.; Bruckert, Eric; Vohnout, Branislav; Schreier, Laura; Pang, Jing; Ebenbichler, Christoph; Dieplinger, Hans; Innerhofer, Reinhold; Winhofer-Stöckl, Yvonne; Greber-Platzer, Susanne; Krychtiuk, Konstantin; Speidl, Walter; Toplak, Hermann; Widhalm, Kurt; Stulnig, Thomas; Huber, Kurt; Höllerl, Florian; Rega-Kaun, Gersina; Kleemann, Lucas; Mäser, Martin; Scholl-Bürgi, Sabine; Säly, Christoph; Mayer, Florian J.; Sablon, Gaelle; Tarantino, Eric; Nzeyimana, Charlotte; Pojskic, Lamija; Sisic, Ibrahim; Nalbantic, Azra D.; Jannes, Cinthia E.; Pereira, Alexandre C.; Krieger, Jose E.; Petrov, Ivo; Goudev, Assen; Nikolov, Fedya; Tisheva, Snejana; Yotov, Yoto; Tzvetkov, Ivajlo; Baass, Alexis; Bergeron, Jean; Bernard, Sophie; Brisson, Diane; Brunham, Liam R.; Cermakova, Lubomira; Couture, Patrick; Francis, Gordon A.; Gaudet, Daniel; Hegele, Robert A.; Khoury, Etienne; Mancini, G.B. John; McCrindle, Brian W.; Paquette, Martine; Ruel, Isabelle; Cuevas, Ada; Asenjo, Sylvia; Wang, Xumin; Meng, Kang; Song, Xiantao; Yong, Qiang; Jiang, Tao; Liu, Ziyou; Duan, Yanyu; Hong, Jing; Ye, Pucong; Chen, Yan; Qi, Jianguang; Liu, Zesen; Li, Yuntao; Zhang, Chaoyi; Peng, Jie; Yang, Ya; Yu, Wei; Wang, Qian; Yuan, Hui; Cheng, Shitong; Jiang, Long; Chong, Mei; Jiao, Jian; Wu, Yue; Wen, Wenhui; Xu, Liyuan; Zhang, Ruiying; Qu, Yichen; He, Jianxun; Fan, Xuesong; Wang, Zhenjia; Chow, Elaine; Pećin, Ivan; Perica, Dražen; Symeonides, Phivos; Vrablik, Michal; Ceska, Richard; Soska, Vladimir; Tichy, Lukas; Adamkova, Vera; Franekova, Jana; Cifkova, Renata; Kraml, Pavel; Vonaskova, Katerina; Cepova, Jana; Dusejovska, Magdalena; Pavlickova, Lenka; Blaha, Vladimir; Rosolova, Hana; Nussbaumerova, Barbora; Cibulka, Roman; Vaverkova, Helena; Cibickova, Lubica; Krejsova, Zdenka; Rehouskova, Katerina; Malina, Pavel; Budikova, Milena; Palanova, Vaclava; Solcova, Lucie; Lubasova, Alena; Podzimkova, Helena; Bujdak, Juraj; Vesely, Jiri; Jordanova, Marta; Salek, Tomas; Urbanek, Robin; Zemek, Stanislav; Lacko, Jan; Halamkova, Hana; Machacova, Sona; Mala, Sarka; Cubova, Eva; Valoskova, Katerina; Burda, Lukas; Bendary, Ahmed; Daoud, Ihab; Emil, Sameh; Elbahry, Atef; Rafla, Samir; Sanad, Osama; Kazamel, Ghada; Ashraf, Mohamed; Sobhy, Mohamed; El-Hadidy, Amro; Shafy, Mohamed A.; Kamal, Saif; Bendary, Mohamed; Talviste, Grete; Angoulvant, Denis; Boccara, Franck; Cariou, Bertrand; Carreau, Valérie; Carrie, Alain; Charrieres, Sybil; Cottin, Yves; Di-Fillipo, Mathilde; Ducluzeau, Pierre H.; Dulong, Sonia; Durlach, Vincent; Farnier, Michel; Ferrari, Emile; Ferrieres, Dorota; Ferrieres, Jean; Gallo, Antonio; hankard, Regis; Inamo, Jocelyne; Lemale, Julie; Moulin, Philippe; Paillard, François; Peretti, Noel; Perrin, Agnès; Pradignac, Alain; Rabes, Jean P.; Rigalleau, Vincent; Sultan, Ariane; Schiele, François; Tounian, Patrick; Valero, René; Verges, Bruno; Yelnik, Cécile; Ziegler, Olivier; Haack, Ira A.; Schmidt, Nina; Dressel, Alexander; Klein, Isabel; Christmann, Jutta; Sonntag, Antonia; Stumpp, Christine; Boger, Diana; Biedermann, Dana; Usme, Monica M.N.; Beil, F. Ulrich; Klose, Gerald; König, Christel; Gouni-Berthold, Ioanna; Otte, Britta; Böll, Gereon; Kirschbaum, Anja; Merke, Jürgen; Scholl, Johannes; Segiet, Thomas; Gebauer, Marco; Predica, Florentina; Mayer, Manfred; Leistikow, Frank; Füllgraf-Horst, Sabine; Müller, Cornelius; Schüler, Melanie; Wiener, Judith; Hein, Konrad; Baumgartner, Peter; Kopf, Stefan; Busch, Reinhold; Schömig, Michael; Matthias, Stephan; Allendorf-Ostwald, Nicole; Fink, Bruno; Böhm, Dieter; Jäkel, Alexander; Koschker, Ann-Cathrin; Schweizer, Rüdiger; Vogt, Anja; Parhofer, Klaus; König, Wolfgang; Reinhard, Wibke; Bäßler, Andrea; Stadelmann, Alexander; Schrader, Volker; Katzmann, Julius; Tarr, Adrienne; Steinhagen-Thiessen, Elisabeth; Kassner, Ursula; Paulsen, Gerret; Homberger, Jürgen; Zemmrich, Claudia; Seeger, Wolfgang; Biolik, Kathrin; Deiss, Dorothee; Richter, Corinna; Pantchechnikova, Elina; Dorn, Elena; Schatz, Ulrike; Julius, Ulrich; Spens, Antje; Wiesner, Tobias; Scholl, Michael; Rizos, Christos V.; Sakkas, Nikolaos; Elisaf, Moses; Skoumas, Ioannis; Tziomalos, Konstantinos; Rallidis, Loukianos; Kotsis, Vasileios; Doumas, Michalis; Athyros, Vasileios; Skalidis, Emmanouil; Kolovou, Genovefa; Garoufi, Anastasia; Bilianou, Eleni; Koutagiar, Iosif; Agapakis, Dimitrios; Kiouri, Estela; Antza, Christina; Katsiki, Niki; Zacharis, Evangelos; Attilakos, Achilleas; Sfikas, George; Koumaras, Charalambos; Anagnostis, Panagiotis; Anastasiou, Georgia; Liamis, George; Koutsogianni, Amalia-Despoina; Karányi, Zsolt; Harangi, Mariann; Bajnok, László; Audikovszky, Mária; Márk, László; Benczúr, Béla; Reiber, István; Nagy, Gergely; Nagy, András; Reddy, Lakshmi L.; Shah, Swarup A.V.; Ponde, Chandrashekhar K.; Dalal, Jamshed J.; Sawhney, Jitendra P.S.; Verma, Ishwar C.; Altaey, Mays; Al-Jumaily, Khalid; Rasul, Dilshad; Abdalsahib, Ali F.; Jabbar, Amer A.; Al-ageedi, Mohanad; Agar, Ruth; Cohen, Hofit; Ellis, Avishay; Gavishv, Dov; Harats, Dror; Henkin, Yaacov; Knobler, Hila; Leavit, Leah; Leitersdorf, Eran; Rubinstein, Ardon; Schurr, Daniel; Shpitzen, Shoshi; Szalat, Auryan; Casula, Manuela; Zampoleri, Veronica; Gazzotti, Marta; Olmastroni, Elena; Sarzani, Riccardo; Ferri, Claudio; Repetti, Elena; Sabbà, Carlo; Bossi, Antonio Carlo; Borghi, Claudio; Muntoni, Sandro; Cipollone, Francesco; Purrello, Francesco; Pujia, Arturo; Passaro, Angelina; Marcucci, Rossella; Pecchioli, Valerio; Pisciotta, Livia; Mandraffino, Giuseppe; Pellegatta, Fabio; Mombelli, Giuliana; Branchi, Adriana; Fiorenza, Anna Maria; Pederiva, Cristina; Werba, Josè Pablo; Parati, Gianfranco; Carubbi, Francesca; Iughetti, Lorenzo; Iannuzzi, Arcangelo; Iannuzzo, Gabriella; Calabrò, Paolo; Averna, Maurizio; Biasucci, Giacomo; Zambon, Sabina; Roscini, Anna Rita; Trenti, Chiara; Arca, Marcello; Federici, Massimo; Del Ben, Maria; Bartuli, Andrea; Giaccari, Andrea; Pipolo, Antonio; Citroni, Nadia; Guardamagna, Ornella; Bonomo, Katia; Benso, Andrea; Biolo, Gianni; Maroni, Lorenzo; Lupi, Alessandro; Bonanni, Luca; Zenti, Maria Grazia; Matsuki, Kota; Hori, Mika; Ogura, Masatsune; Masuda, Daisaku; Kobayashi, Takuya; Nagahama, Kumiko; Al-Jarallah, Mohammed; Radovic, Mirjana; Lunegova, Olga; Bektasheva, Erkayim; Khodzhiboboev, Elyor; Erglis, Andrejs; Gilis, Dainus; Nesterovics, Georgijs; Saripo, Vita; Meiere, Ruta; Upena-RozeMicena, Arta; Terauda, Elizabete; Jambart, Selim; Khoury, Petra E.; Elbitar, Sandy; Ayoub, Carine; Ghaleb, Youmna; Aliosaitiene, Urte; Kutkiene, Sandra; Kasim, Noor A.M.; Nor, Noor S.M.; Ramli, Anis S.; Razak, Suraya A.; Al-Khateeb, Alyaa; Kadir, Siti H.S.A.; Muid, Suhaila A.; Rahman, Thuhairah A.; Kasim, Sazzli S.; Radzi, Ahmad B.M.; Ibrahim, Khairul S.; Razali, Salmi; Ismail, Zaliha; Ghani, Rohana A.; Hafidz, Muhammad I.A.; Chua, Ang L.; Rosli, Marshima M.; Annamalai, Muthukkaruppan; Teh, Lay K.; Razali, Rafezah; Chua, Yung A.; Rosman, Azhari; Sanusi, Abdul R.; Murad, Nor A.A.; Jamal, A. Rahman A.; Nazli, Sukma A.; Razman, Aimi Z.; Rosman, Norhidayah; Rahmat, Radzi; Hamzan, Nur S.; Azzopardi, C.; Mehta, Roopa; Martagon, Alexandro J.; Ramirez, Gabriela A.G.; Villa, Neftali E.A.; Vazquez, Arsenio V.; Elias-Lopez, Daniel; Retana, Gustavo G.; Rodriguez, Betsabel; Macías, Jose J.C.; Zazueta, Alejandro R.; Alvarado, Rocio M.; Portano, Julieta D.M.; Lopez, Humberto A.; Sauque-Reyna, Leobardo; Herrera, Laura G.G.; Mendia, Luis E.S.; Aguilar, Humberto Garcia; Cooremans, Elizabeth R.; Aparicio, Berenice P.; Zubieta, Victoria M.; Gonzalez, Perla A.C.; Ferreira-Hermosillo, Aldo; Portilla, Nacu C.; Dominguez, Guadalupe J.; Garcia, Alinna Y.R.; Cazares, Hector E.A.; Gonzalez, Jesus R.; Valencia, Carla V.M.; Padilla, Francisco G.; Prado, Ramon M.; De los Rios Ibarra, Manuel O.; Villicaña, Ruy D.A.; Rivera, Karina J.A.; Carrera, Ricardo A.; Alvarez, Jose A.; Martinez, Jose C.A.; de los Reyes Barrera Bustillo, Manuel; Vargas, Gonzalo C.; Chacon, Roberto C.; Andrade, Mario H.F.; Ortega, Ashanty F.; Alcala, Hector G.; de Leon, Laura E.G.; Guzman, Berenice G.; Garcia, Jose J.G.; Cuellar, Juan C.G.; Cruz, Jose R.G.; Garcia, Anell Hernandez; Almada, Jesus R.H.; Herrera, Ursulo J.; Sobrevilla, Fabiola L.; Rodriguez, Eduardo M.; Sibaja, Cristina M.; Rodriguez, Alma B.M.; Oyervides, Jose C.M.; Vazquez, Daniel I.P.; Rodriguez, Eduardo A.R.; Osorio, Ma L.R.; Saucedo, Juan R.; Tamayo, Margarita T.; Talavera, Luis A.V.; Arroyo, Luis E.V.; Carrillo, Eloy A.Z.; Isara, Alphonsus; Obaseki, Darlington E.; Al-Waili, Khalid; Al-Zadjali, Fahad; Al-Zakwani, Ibrahim; Al-Kindi, Mohammed; Al-Mukhaini, Suad; Al-Barwani, Hamida; Rana, Asim; Shah, Lahore S.U.; Starostecka, Ewa; Konopka, Agnieszka; Lewek, Joanna; Bartłomiejczyk, Marcin; Gąsior, Mariusz; Dyrbuś, Krzysztof; Jóźwiak, Jacek; Gruchała, Marcin; Pajkowski, Marcin; Romanowska-Kocejko, Marzena; Żarczyńska-Buchowiecka, Marta; Chmara, Magdalena; Wasąg, Bartosz; Parczewska, Aleksandra; Gilis-Malinowska, Natasza; Borowiec-Wolna, Justyna; Stróżyk, Aneta; Woś, Marlena; Michalska-Grzonkowska, Aleksandra; Medeiros, Ana M.; Alves, Ana C.; Silva, Francisco; Lobarinhas, Goreti; Palma, Isabel; de Moura, Jose P.; Rico, Miguel T.; Rato, Quitéria; Pais, Patrícia; Correia, Susana; Moldovan, Oana; Virtuoso, Maria J.; Salgado, Jose M.; Colaço, Ines; Dumitrescu, Andreea; Lengher, Calin; Mosteoru, Svetlana; Meshkov, Alexey; Ershova, Alexandra; Rozkova, Tatiana; Korneva, Victoria; Yu, Kuznetsova T.; Zafiraki, Vitaliy; Voevoda, Mikhail; Gurevich, Victor; Duplyakov, Dmitry; Ragino, Yulia; Safarova, Maya; Shaposhnik, Igor; Alkaf, Fahmi; Khudari, Alia; Rwaili, Nawal; Al-Allaf, Faisal; Alghamdi, Mohammad; Batais, Mohammed A.; Almigbal, Turky H.; Kinsara, Abdulhalim; AlQudaimi, Ashraf H.A.; Awan, Zuhier; Elamin, Omer A.; Altaradi, Hani; Rajkovic, Natasa; Popovic, Ljiljana; Singh, Sandra; Stosic, Ljubica; Rasulic, Iva; Lalic, Nebojsa M.; Lam, Carolyn; Le, Tan J.; Siang, Eric L.T.; Dissanayake, Sanjaya; I-Shing, Justin T.; Shyong, Tai E.; Jin, Terrance C.S.; Balinth, Karin; Buganova, Ingrid; Fabryova, Lubomira; Kadurova, Michaela; Klabnik, Alexander; Kozárová, Miriam; Sirotiakova, Jana; Battelino, Tadej; Kovac, Jernej; Mlinaric, Matej; Sustar, Ursa; Podkrajsek, Katarina T.; Fras, Zlatko; Jug, Borut; Cevc, Matija; Pilcher, Gillian J.; Blom, D.J.; Wolmarans, K.H.; Brice, B.C.; Muñiz-Grijalvo, Ovidio; Díaz-Díaz, Jose L.; de Isla, Leopoldo P.; Fuentes, Francisco; Badimon, Lina; Martin, François; Lux, Angela; Chang, Nien-Tzu; Ganokroj, Poranee; Akbulut, Mehmet; Alici, Gökhan; Bayram, Fahri; Can, Levent H.; Celik, Ahmet; Ceyhan, Ceyhun; Coskun, Fatma Y.; Demir, Mesut; Demircan, Sabri; Dogan, Volkan; Durakoglugil, Emre; Dural, Ibrahim E.; Gedikli, Omer; Hacioglu, Aysa; Ildizli, Muge; Kilic, Salih; Kirilmaz, Bahadir; Kutlu, Merih; Oguz, Aytekin; Ozdogan, Oner; Onrat, Ersel; Ozer, Savas; Sabuncu, Tevfik; Sahin, Tayfun; Sivri, Fatih; Sonmez, Alper; Temizhan, Ahmet; Topcu, Selim; Tuncez, Abdullah; Vural, Mirac; Yenercag, Mustafa; Yesilbursa, Dilek; Yigit, Zerrin; Yildirim, Aytul B.; Yildirir, Aylin; Yilmaz, Mehmet B.; Atallah, Bassam; Traina, Mahmoud; Sabbour, Hani; Hay, Dana A.; Luqman, Neama; Elfatih, Abubaker; Abdulrasheed, Arshad; Kwok, See; Oca, Nicolas D.; Reyes, Ximena; Alieva, Rano B.; Kurbanov, Ravshanbek D.; Hoshimov, Shavkat U.; Nizamov, Ulugbek I.; Ziyaeva, Adolat V.; Abdullaeva, Guzal J.; Do, Doan L.; Nguyen, Mai N.T.; Kim, Ngoc T.; Le, Thanh T.; Le, Hong A.; Tokgozoglu, Lale; Catapano, Alberico L.; Ray, Kausik K.Vallejo-Vaz, Antonio J.; Stevens, Christophe A. T.; Lyons, Alexander R. M.; Dharmayat, Kanika I.; Freiberger, Tomas; Hovingh, G. Kees; Mata, Pedro; Raal, Frederick J.; Santos, Raul D.; Soran, Handrean; Watts, Gerald F.; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alhabib, Khalid F.; Alkhnifsawi, Mutaz; Almahmeed, Wael; Alnouri, Fahad; Alonso, Rodrigo; Al-Rasadi, Khalid; Al-Sarraf, Ahmad; Al-Sayed, Nasreen; Araujo, Francisco; Ashavaid, Tester F.; Banach, Maciej; Béliard, Sophie; Benn, Marianne; Binder, Christoph J.; Bogsrud, Martin P.; Bourbon, Mafalda; Chlebus, Krzysztof; Corral, Pablo; Davletov, Kairat; Descamps, Olivier S.; Durst, Ronen; Ezhov, Marat; Gaita, Dan; Genest, Jacques; Groselj, Urh; Harada-Shiba, Mariko; Holven, Kirsten B.; Kayikcioglu, Meral; Khovidhunkit, Weerapan; Lalic, Katarina; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lima-Martinez, Marcos M.; Lin, Jie; Maher, Vincent; Marais, A. David; März, Winfried; Mirrakhimov, Erkin; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah; Nordestgaard, Børge G.; Panayiotou, Andrie G.; Paragh, György; Petrulioniene, Zaneta; Pojskic, Belma; Postadzhiyan, Arman; Raslova, Katarina; Reda, Ashraf; Reiner, Željko; Sadiq, Fouzia; Sadoh, Wilson Ehidiamen; Schunkert, Heribert; Shek, Aleksandr B.; Stoll, Mario; Stroes, Erik; Su, Ta-Chen; Subramaniam, Tavintharan; Susekov, Andrey V.; Tilney, Myra; Tomlinson, Brian; Truong, Thanh Huong; Tselepis, Alexandros D.; Tybjærg-Hansen, Anne; Vázquez Cárdenas, Alejandra; Viigimaa, Margus; Wang, Luya; Yamashita, Shizuya; Kastelein, John J. P.; Bruckert, Eric; Vohnout, Branislav; Schreier, Laura; Pang, Jing; Ebenbichler, Christoph; Dieplinger, Hans; Innerhofer, Reinhold; Winhofer-Stöckl, Yvonne; Greber-Platzer, Susanne; Krychtiuk, Konstantin; Speidl, Walter; Toplak, Hermann; Widhalm, Kurt; Stulnig, Thomas; Huber, Kurt; Höllerl, Florian; Rega-Kaun, Gersina; Kleemann, Lucas; Mäser, Martin; Scholl-Bürgi, Sabine; Säly, Christoph; Mayer, Florian J.; Sablon, Gaelle; Tarantino, Eric; Nzeyimana, Charlotte; Pojskic, Lamija; Sisic, Ibrahim; Nalbantic, Azra D.; Jannes, Cinthia E.; Pereira, Alexandre C.; Krieger, Jose E.; Petrov, Ivo; Goudev, Assen; Nikolov, Fedya; Tisheva, Snejana; Yotov, Yoto; Tzvetkov, Ivajlo; Baass, Alexis; Bergeron, Jean; Bernard, Sophie; Brisson, Diane; Brunham, Liam R.; Cermakova, Lubomira; Couture, Patrick; Francis, Gordon A.; Gaudet, Daniel; Hegele, Robert A.; Khoury, Etienne; Mancini, G. B. John; Mccrindle, Brian W.; Paquette, Martine; Ruel, Isabelle; Cuevas, Ada; Asenjo, Sylvia; Wang, Xumin; Meng, Kang; Song, Xiantao; Yong, Qiang; Jiang, Tao; Liu, Ziyou; Duan, Yanyu; Hong, Jing; Ye, Pucong; Chen, Yan; Qi, Jianguang; Liu, Zesen; Li, Yuntao; Zhang, Chaoyi; Peng, Jie; Yang, Ya; Yu, Wei; Wang, Qian; Yuan, Hui; Cheng, Shitong; Jiang, Long; Chong, Mei; Jiao, Jian; Wu, Yue; Wen, Wenhui; Xu, Liyuan; Zhang, Ruiying; Qu, Yichen; He, Jianxun; Fan, Xuesong; Wang, Zhenjia; Chow, Elaine; Pećin, Ivan; Perica, Dražen; Symeonides, Phivos; Vrablik, Michal; Ceska, Richard; Soska, Vladimir; Tichy, Lukas; Adamkova, Vera; Franekova, Jana; Cifkova, Renata; Kraml, Pavel; Vonaskova, Katerina; Cepova, Jana; Dusejovska, Magdalena; Pavlickova, Lenka; Blaha, Vladimir; Rosolova, Hana; Nussbaumerova, Barbora; Cibulka, Roman; Vaverkova, Helena; Cibickova, Lubica; Krejsova, Zdenka; Rehouskova, Katerina; Malina, Pavel; Budikova, Milena; Palanova, Vaclava; Solcova, Lucie; Lubasova, Alena; Podzimkova, Helena; Bujdak, Juraj; Vesely, Jiri; Jordanova, Marta; Salek, Tomas; Urbanek, Robin; Zemek, Stanislav; Lacko, Jan; Halamkova, Hana; Machacova, Sona; Mala, Sarka; Cubova, Eva; Valoskova, Katerina; Burda, Lukas; Bendary, Ahmed; Daoud, Ihab; Emil, Sameh; Elbahry, Atef; Rafla, Samir; Sanad, Osama; Kazamel, Ghada; Ashraf, Mohamed; Sobhy, Mohamed; El-Hadidy, Amro; Shafy, Mohamed A.; Kamal, Saif; Bendary, Mohamed; Talviste, Grete; Angoulvant, Denis; Boccara, Franck; Cariou, Bertrand; Carreau, Valérie; Carrie, Alain; Charrieres, Sybil; Cottin, Yves; Di-Fillipo, Mathilde; Ducluzeau, Pierre H.; Dulong, Sonia; Durlach, Vincent; Farnier, Michel; Ferrari, Emile; Ferrieres, Dorota; Ferrieres, Jean; Gallo, Antonio; Hankard, Regis; Inamo, Jocelyne; Lemale, Julie; Moulin, Philippe; Paillard, François; Peretti, Noel; Perrin, Agnès; Pradignac, Alain; Rabes, Jean P.; Rigalleau, Vincent; Sultan, Ariane; Schiele, François; Tounian, Patrick; Valero, René; Verges, Bruno; Yelnik, Cécile; Ziegler, Olivier; Haack, Ira A.; Schmidt, Nina; Dressel, Alexander; Klein, Isabel; Christmann, Jutta; Sonntag, Antonia; Stumpp, Christine; Boger, Diana; Biedermann, Dana; Usme, Monica M. N.; Beil, F. Ulrich; Klose, Gerald; König, Christel; Gouni-Berthold, Ioanna; Otte, Britta; Böll, Gereon; Kirschbaum, Anja; Merke, Jürgen; Scholl, Johannes; Segiet, Thomas; Gebauer, Marco; Predica, Florentina; Mayer, Manfred; Leistikow, Frank; Füllgraf-Horst, Sabine; Müller, Cornelius; Schüler, Melanie; Wiener, Judith; Hein, Konrad; Baumgartner, Peter; Kopf, Stefan; Busch, Reinhold; Schömig, Michael; Matthias, Stephan; Allendorf-Ostwald, Nicole; Fink, Bruno; Böhm, Dieter; Jäkel, Alexander; Koschker, Ann-Cathrin; Schweizer, Rüdiger; Vogt, Anja; Parhofer, Klaus; König, Wolfgang; Reinhard, Wibke; Bäßler, Andrea; Stadelmann, Alexander; Schrader, Volker; Katzmann, Julius; Tarr, Adrienne; Steinhagen-Thiessen, Elisabeth; Kassner, Ursula; Paulsen, Gerret; Homberger, Jürgen; Zemmrich, Claudia; Seeger, Wolfgang; Biolik, Kathrin; Deiss, Dorothee; Richter, Corinna; Pantchechnikova, Elina; Dorn, Elena; Schatz, Ulrike; Julius, Ulrich; Spens, Antje; Wiesner, Tobias; Scholl, Michael; Rizos, Christos V.; Sakkas, Nikolaos; Elisaf, Moses; Skoumas, Ioannis; Tziomalos, Konstantinos; Rallidis, Loukianos; Kotsis, Vasileios; Doumas, Michalis; Athyros, Vasileios; Skalidis, Emmanouil; Kolovou, Genovefa; Garoufi, Anastasi

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)