Intracranial Hemorrhage in the TST Trial
Authors: Amarenco Pierre , Kim Jong S. , Labreuche Julien , Charles Hugo , Giroud Maurice , Lavallée Philippa C. , Lee Byung-Chul , Mahagne Marie-Hélène , Meseguer Elena , Nighoghossian Norbert , Steg Philippe Gabriel , Vicaut Éric , Bruckert Eric , Touboul Pierre-Jean , Leys Didier , Béjot Yannick , Pico Fernando , Touzé Emmanuel , Ducrocq Gregory , Abtan Jérémy , Varenne Olivier , Touboul Pierre-Jean , Kemmel Agnes , Syana Fausta , Ledra Manele , Nagasara Tharani , Ledjeroud Mervette , Samia Bahous , Hadia Hafirassou , Hazare Benyoub , El Jaghouni Ikrame , Yelles Nessima , Zemouri Sofia , Ladjeroud Mervette , Kerai Salim , In YunJeong , Hobeanu Cristina , Guidoux Celine , Cabrejo Lucie , Lapergue Bertrand , Sabben Candice , Gonzalez-Valcarcel Jaime , Rigual Ricardo , Sirimarco Gaia , Martin-Bechet Anna , Viedma Elena , Avram Ioan , Samson Yves , Rosso Charlotte , Crozier Sophie , Leder Sara , Léger Anne , Deltour Sandrine , Mutlu Gurkan , Yger Marion , Zavanone Chiara , Baronnet Flore , Pires Christine , Lapergue Bertrand , Wang Adrien , Evrard Serge , Tchikviladze Maya , Bourdain Frédéric , Lopez Delphine , Pico Fernando , Bayon de la Tour Laetitia , Chadenat Marie-Laure , Duong Duc Long , Genty Solène , Hirel Catherine , Mutlu Gurkan , Nifle Chantal , Servan Jérôme , Stanciu Daniela , Sudacevschi Veronica , Tir Mélissa , Troussière Anne-Cécile , Yeung Jennifer , Zeghoudi Anne-Céline , Tidafi-Bayou Ikram , Lachaud Sylvain , Cho Tae-Hee , Mechtouff Laura , Ritzenthaller Thomas , Derex Laurent , Albanesi Carlo , Ong Elodie , Benoit Amandine , Berhoune Nadia , Felix Sandra , Esteban-Mader Maud , Sibon Igor , Kazadi Annabelle , Rouanet François , Renou Pauline , Debruxelles Sabrina , Poli Mathilde , Sagnier Sharmila , Mas Jean-Louis , Domigo Valérie , Lamy Catherine , Bodiguel Eric , Grimaud Jérôme , Bohotin Valentin , Obadia Michael , Sabben Candice , Morvan Erwan , Rodier Gilles , Vadot Wilfried , Hénon Hilde , Cordonnier Charlotte , Dumont Frédéric , Bodenant Marie , Lucas Christian , Moulin Solène , Dequatre Nelly , Alamowitch Sonia , Muresan Jean-Paul , Drouet Thomas , Gallea Magalie , Dalloz Marie-Amélie , Delorme Stephen , Yger Marion , Béjot Yannick , Loisel Philippe , Bonnin Carine , Bernigal Virginie , Victor Osseby Guy , Hervieu-BègueMarsac Marie , Garnier Pierre , Accassat Sandrine , Epinat Magali , Varvat Jérôme , Marinescu Doïna , Triquenot-Bagan Aude , Ozkul- Wermester Ozlem , Philippeau Frédéric , Vieillart Anne , Lannuzel Annie , Demoly Alice , Wolff Valérie , Diaconu Mihaela , Bataillard Marc , Macian Montoro Francisco , Faugeras Frédéric , Gimenez Laeticia , Abdallah-Lebeau Françoise , Timsit Serge , Viakhireva-Dovganyuk Irina , Tirel-Badets Anne , Merrien François-Mathias , Goas Philippe , Rouhart François , Jourdain Aurore , Guillon Benoit , Hérissson Fanny , Sevin-Allouet Mathieu , Nasr Nathalie , Olivot Jean-Marc , Lecluse Alderic , Marc Guillaume , Hamon  , Touzé Emmanuel , de la Sayette Vincent , Apoil Marion , Lin Li , Cogez Julien , Guettier Sophie , Godefroy Olivier , Lamy Chantal , Bugnicourt Jean-Marc , Taurin Grégory , Mérienne Marc , Gere Julien , Chessak Anne-Marie , Habet Tarik , Ferrier Anna , Bourgois Nathalie , Minier Dominique , Caillier-Minier Marie , Contégal- Callier Fabienne , Vion Philippe , Vaschalde Yvan , El Amrani Mohammed , Emilie  , Zuber Mathieu , Bruandet Marie , Join- Lambert Claire , Garcia Pierre-Yves , Serre Isabelle , Faucheux Jean-Marc , Radji Fatia , Leca-Radu Elena , Debroucker Thomas , Cumurcuc Rodica , Cakmak Serkan , Peysson Stéphane , Ellie Emmanuel , Bernady Patricia , Moulin Thierry , Montiel Paola , Revenco Eugeniu , Decavel Pierre , Medeiros Elisabeth , Bouveret Myriam , Louchart Pierre , Vaduva Claudia , Couvreur Grégory , Sartori Eric , Alnajar-Carpentier  , Levasseur Michèle , Louchart Pierre , Neau Jean-Philippe , Vandamme Xavier , Meresse Isabelle , Stantescu  , Bataillard Marc , Ozsancak Canan , Beauvais Katell , Auzou Pascal , Amevigbe Joséphine , Vuillemet Francis , Dugay-Arentz, Marie-Hélène , Carelli Gabriela , Martinez Mikel , Maillet-Vioud Marcel , Escaillas Jean-Pierre , Chapuis Stéphane , Tardy Jean , Manchon Eric , Varnet Olivier , Kim Yong-Jae , Chang Yoonkyung , Song Tae-Jin , Kim Jong Sung , Han Jung-Hoon , Chul Noh Kyung , Lee Eun-Jae , Kang Dong-Wha , Uck Kwon Sun , Kwon Boseoung , Park Seongho , Lee Dongwhane , Sung Kwon Hyuk , Jeong Daeun , Lee MinHwan , Kim Joonggoo , Lee Hanbin , Jung Nam, Hyo , Hun Lee Sang , Joon Kim Bum , Cha Jae-kwan , Kim DaeHyun , Kim Rae Young , Sohn Sang Wuk , Shim Dong-Hyun , Lee Hyungjin , Nah Hyun-Wook , Sung Sang Min , Lee Kyung Bok , Lee Jeong Yoon , Yoon Jee Eun , Kim Eung-Gyu , Seo Jung Hwa , Kim Yong-Won , Hwang Yangha , Park Man Seok , Kim Joon-Tae , Choi Kang-Ho , Nam Hyo Suk , Heo Ji Hoe , Dae Kim Young , Gun Hwang In , Park Hyung Jong , Kim Kyoung Sub , Baek Jang Hyun , Song Dong Beom , Yoo Joon Sang , Park Jong-Moo , Kwon Ohyun , Lee Woong-Woo , Lee Jung-Ju , Kang Kyusik , Kim Byung Kun , Lim Jae-Sung , Sun Oh Mi , Yu Kyung-Ho , Hong Bora , Jang Mihoon , Jang Seyoung , Jin Jung Eun , Kim Jei , Jeong Hye Seon , Hong Keun Sik , Park Hong Kyun , Jin Cho Yong , Bang Oh Young , Seo Keun , Chung Jongwon 
Published: December 2021

Background and Purpose:
Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH.

Methods:
Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of <70 mg/dL or 100±10 mg/dL, using statin or ezetimibe.

Results:

Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38–4.04] and 2.32/1000 patient-years [95% CI, 1.61–3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01–6.31],
P
=0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00–5.62],
P
=0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH.

Conclusions:
Targeting an LDL cholesterol of <70 mg/dL compared with 100±10 mg/dL in patients with atherosclerotic ischemic stroke nonsignificantly increased the risk of ICH. Incident ICHs were not associated with low LDL cholesterol. Uncontrolled hypertension and anticoagulant therapy were associated with ICH which has important clinical implications.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.