Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol Pierre Amarenco  1 , Jong S Kim  2 , Julien Labreuche  1 , Hugo Charles  1 , Maurice Giroud  3 , Byung-Chul Lee  4 , Marie-Hélène Mahagne  5 , Norbert Nighoghossian  6 , Philippe Gabriel Steg  7 , Éric Vicaut  8   9 , Eric Bruckert  10 ; Treat Stroke to Target Investigators Collaborators, Affiliations Expand Collaborators Treat Stroke to Target Investigators: Pierre-Jean Touboul, Didier Leys, Yannick Béjot, Philippa Lavallée, Fernando Pico, Emmanuel Touzé, Gregory Ducrocq, Jérémy Abtan, Olivier Varenne, Pierre-Jean Touboul, Agnes Kemmel, Fausta Syana, Manele Ledra, Tharani Nagasara, Mervette Ledjeroud, Bahous Samia, Hafirassou Hadia, Benyoub Hazare, Ikrame El Jaghouni, Nessima Yelles, Sofia Zemouri, Mervette Ladjeroud, Salim Kerai, Yun Jeong In, Elena Meseguer, Philippa C Lavallée, Cristina Hobeanu, Celine Guidoux, Lucie Cabrejo, Bertrand Lapergue, Candice Sabben, Jaime Gonzalez-Valcarcel, Ricardo Rigual, Gaia Sirimarco, Anna Martin-Bechet, Elena Viedma, Ioan Avram, Yves Samson, Charlotte Rosso, Sophie Crozier, Sara Leder, Anne Léger, Sandrine Deltour, Gurkan Mutlu, Marion Yger, Chiara Zavanone, Flore Baronnet, Christine Pires, Bertrand Lapergue, Adrien Wang, Serge Evrard, Maya Tchikviladze, Frédéric Bourdain, Delphine Lopez, Fernando Pico, Laetitia Bayon de la Tour, Marie-Laure Chadenat, Duc Long Duong, Solène Genty, Catherine Hirel, Gurkan Mutlu, Chantal Nifle, Jérôme Servan, Daniela Stanciu, Veronica Sudacevschi, Mélissa Tir, Anne-Cécile Troussière, Jennifer Yeung, Anne-Céline Zeghoudi, Ikram Tidafi-Bayou, Sylvain Lachaud, Tae-Hee Cho, Laura Mechtouff, Thomas Ritzenthaller, Laurent Derex, Carlo Albanesi, Elodie Ong, Amandine Benoit, Nadia Berhoune, Sandra Felix, Maud Esteban-Mader, Igor Sibon, Annabelle Kazadi, François Rouanet, Pauline Renou, Sabrina Debruxelles, Mathilde Poli, Sharmila Sagnier, Jean-Louis Mas, Valérie Domigo, Catherine Lamy, Eric Bodiguel, Jérôme Grimaud, Valentin Bohotin, Michael Obadia, Candice Sabben, Erwan Morvan, Gilles Rodier, Wilfried Vadot, Hilde Hénon, Charlotte Cordonnier, Frédéric Dumont, Marie Bodenant, Christian Lucas, Solène Moulin, Nelly Dequatre, Sonia Alamowitch, Jean-Paul Muresan, Thomas Drouet, Magalie Gallea, Marie-Amélie Dalloz, Stephen Delorme, Marion Yger, Yannick Béjot, Philippe Loisel, Carine Bonnin, Virginie Bernigal, Guy Victor Osseby, Marie Hervieu-Bègue Marsac, Pierre Garnier, Sandrine Accassat, Magali Epinat, Jérôme Varvat, Doïna Marinescu, Aude Triquenot-Bagan, Ozlem Ozkul-Wermester, Frédéric Philippeau, Angel Olaru, Anne Vieillart, Annie Lannuzel, Alice Demoly, Valérie Wolff, Mihaela Diaconu, Marc Bataillard, Francisco Macian Montoro, Frédéric Faugeras, Laeticia Gimenez, Françoise Abdallah-Lebeau, Serge Timsit, Irina Viakhireva-Dovganyuk, Anne Tirel-Badets, François-Mathias Merrien, Philippe Goas, François Rouhart, Aurore Jourdain, Benoit Guillon, Fanny Hérissson, Mathieu Sevin-Allouet, Nathalie Nasr, Jean-Marc Olivot, Alderic Lecluse, Guillaume Marc, Emmanuel Touzé, Vincent de la Sayette, Marion Apoil, Li Lin, Julien Cogez, Sophie Guettier, Olivier Godefroy, Chantal Lamy, Jean-Marc Bugnicourt, Grégory Taurin, Marc Mérienne, Julien Gere, Anne-Marie Chessak, Tarik Habet, Anna Ferrier, Nathalie Bourgois, Dominique Minier, Marie Caillier-Minier, Fabienne Contégal-Callier, Philippe Vion, Yvan Vaschalde, Mohammed El Amrani Emilie, Mathieu Zuber, Marie Bruandet, Claire Join-Lambert, Pierre-Yves Garcia, Isabelle Serre, Jean-Marc Faucheux, Fatia Radji, Elena Leca-Radu, Thomas Debroucker, Rodica Cumurcuc, Serkan Cakmak, Stéphane Peysson, Emmanuel Ellie, Patricia Bernady, Thierry Moulin, Paola Montiel, Eugeniu Revenco, Pierre Decavel, Elisabeth Medeiros, Myriam Bouveret, Pierre Louchart, Claudia Vaduva, Grégory Couvreur, Eric Sartori, Eric Alnajar-Carpentier, Michèle Levasseur, Pierre Louchart, Jean-Philippe Neau, Xavier Vandamme, Isabelle Meresse, Stantescu, Marc Bataillard, Canan Ozsancak, Katell Beauvais, Pascal Auzou, Joséphine Amevigbe, Francis Vuillemet, Marie-Hélène Dugay-Arentz, Gabriela Carelli, Mikel Martinez, Marcel Maillet-Vioud, Jean-Pierre Escaillas, Stéphane Chapuis, Jean Tardy, Eric Manchon, Olivier Varnet, Yong-Jae Kim, Yoonkyung Chang, Tae-Jin Song, Jung-Hoon Han, Kyung Chul Noh, Eun-Jae Lee, Dong-Wha Kang, Sun Uck Kwon, Boseoung Kwon, Seongho Park, Dongwhane Lee, Hyuk Sung Kwon, Daeun Jeong, MinHwan Lee, Joonggoo Kim, Hanbin Lee, Hyo Jung Nam, Sang Hun Lee, Bum Joon Kim, Jae-Kwan Cha, DaeHyun Kim, Rae Young Kim, Sang Wuk Sohn, Dong-Hyun Shim, Hyungjin Lee, Hyun-Wook Nah, Sang Min Sung, Kyung Bok Lee, Jeong Yoon Lee, Jee Eun Yoon, Eung-Gyu Kim, Jung Hwa Seo, Yong-Won Kim, Yangha Hwang, Man Seok Park, Joon-Tae Kim, Kang-Ho Choi, Hyo Suk Nam, Ji Hoe Heo, Young Dae Kim, In Gun Hwang, Hyung Jong Park, Kyoung Sub Kim, Jang Hyun Baek, Dong Beom Song, Joon Sang Yoo, Jong-Moo Park, Ohyun Kwon, Woong-Woo Lee, Jung-Ju Lee, Kyusik Kang, Byung Kun Kim, Jae-Sung Lim, Mi Sun Oh, Kyung-Ho Yu, Bora Hong, Mihoon Jang, Seyoung Jang, Jung Eun Jin, Jei Kim, Hye Seon Jeong, Keun Sik Hong, Hong Kyun Park, Yong Jin Cho, Oh Young Bang, Woo-Keun Seo, Jongwon Chung Affiliations 1 From the APHP, Department of Neurology and Stroke center, Bichat Hospital, INSERM LVTS-U1148, DHU FIRE, University of Paris, France (P.A., J.L., H.C.). 2 Asan Medical Center, Seoul, South Korea (J.S.K.). 3 Department of Neurology, University Hospital of Dijon, University of Burgundy, France (M.G.). 4 Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, Korea (B.-C.L.). 5 Stroke Unit, Pasteur Hospital, Nice, France (M.-H.M.). 6 Hospices Civils de Lyon, Department of Neurology and Stroke Center, Lyon University, France (N.N.). 7 APHP, Department of cardiology, INSERM LVTS-U1148, DHU FIRE, University of Paris, Hôpital Bichat, France (P.G.S.). 8 NHLI Imperial College, ICMS Royal Brompton Hospital London, United Kingdom (P.G.S.). 9 APHP, Department of Biostatistics, Université Paris-Diderot, Sorbonne-Paris Cité, Fernand Widal hospital, France (É.V.). 10 APHP, Department of Endocrinology, Pitié-Salpêtrière hospital, Sorbonne University, Paris, France (E.B.). PMID: 32078484 DOI: 10.1161/STROKEAHA.119.028718 Free article Item in Clipboard

Abstract

Background and Purpose- The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of <70 mg/dL to reduce the risk of cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature or aortic arch plaque >4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods- One thousand seventy-three French patients were assigned to <70 mg/dL (1.8 mmol/L) and 1075 to 100±10 mg/dL (90-110 mg/dL, 2.3-2.8 mmol/L). To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe on top if needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. Results- After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57-0.94]; P=0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% (P=0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% (P=0.023). The primary outcome or intracranial hemorrhage was reduced by 25% (P=0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53-2.62]; P=0.70). Conclusions- After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of <70 mg/dL during 5.3 years avoided 1 subsequent major vascular event in 4 (number needed to treat of 30) and no increase in intracranial hemorrhage. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875.

Keywords: angiography; aorta; cholesterol, LDL; informed consent; stroke.