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N Engl J Med. 2020 Jan 2;382(1):9. doi: 10.1056/NEJMoa1910355. Epub 2019 Nov 18.

A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.

Collaborators (288)

Amarenco P, Bruckert E, Giroud M, Kim JS, Labreuche J, Lee BC, Mahagne MH, Nighoghossian N, Steg PG, Touboul PJ, Vicaut E, Leys D, Lavallée P, Ducrocq G, Abtan J, Varenne O, Kemmel A, Syana F, Ledra M, Nagasara T, Ledjeroud M, Samia B, Hadia H, Hazare B, El Jaghouni I, Yelles N, Zemouri S, Ladjeroud M, Kerai S, In Y, Meseguer E, Lavallée PC, Hobeanu C, Guidoux C, Cabrejo L, Gonzalez-Valcarcel J, Rigual R, Sirimarco G, Martin-Bechet A, Viedma E, Avram I, Samson Y, Rosso C, Crozier S, Leder S, Léger A, Deltour S, Zavanone C, Baronnet F, Pires C, Lapergue B, Wang A, Evrard S, Tchikviladze M, Bourdain F, Lopez D, Pico F, de la Tour LB, Chadenat ML, Duong DL, Genty S, Hirel C, Mutlu G, Nifle C, Servan J, Stanciu D, Sudacevschi V, Tir M, Troussière AC, Yeung J, Zeghoudi AC, Tidafi-Bayou I, Lachaud S, Cho TH, Mechtouff L, Ritzenthaller T, Derex L, Albanesi C, Ong E, Benoit A, Berhoune N, Felix S, Esteban-Mader M, Sibon I, Kazadi A, Rouanet F, Renou P, Debruxelles S, Poli M, Sagnier S, Mas JL, Domigo V, Lamy C, Bodiguel E, Grimaud J, Bohotin V, Obadia M, Sabben C, Morvan E, Rodier G, Vadot W, Hénon H, Cordonnier C, Dumont F, Bodenant M, Lucas C, Moulin S, Dequatre N, Alamowitch S, Muresan JP, Drouet T, Gallea M, Dalloz MA, Delorme S, Yger M, Béjot Y, Loisel P, Bonnin C, Bernigal V, Osseby GV, Hervieu-BègueMarsac M, Garnier P, Accassat S, Epinat M, Varvat J, Marinescu D, Triquenot-Bagan A, Ozkul-Wermester O, Philippeau F, Olaru A, Vieillart A, Lannuzel A, Demoly A, Wolff V, Diaconu M, Montoro FM, Faugeras F, Gimenez L, Abdallah-Lebeau F, Timsit S, Viakhireva-Dovganyuk I, Tirel-Badets A, Merrien FM, Goas P, Rouhart F, Jourdain A, Guillon B, Hérissson F, Sevin-Allouet M, Nasr N, Olivot JM, Lecluse A, Marc G, Touzé E, de la Sayette V, Apoil M, Lin L, Cogez J, Guettier S, Godefroy O, Lamy C, Bugnicourt JM, Taurin G, Mérienne M, Gere J, Chessak AM, Habet T, Ferrier A, Bourgois N, Minier D, Caillier-Minier M, Contégal-Callier F, Vion P, Vaschalde Y, El Amrani M, Zuber M, Bruandet M, Join-Lambert C, Garcia PY, Serre I, Faucheux JM, Radji F, Leca-Radu E, Debroucker T, Cumurcuc R, Cakmak S, Peysson S, Ellie E, Bernady P, Moulin T, Montiel P, Revenco E, Decavel P, Medeiros E, Bouveret M, Louchart P, Vaduva C, Couvreur G, Sartori E, Alnajar-Carpentier AA, Levasseur M, Louchart P, Neau JP, Vandamme X, Meresse I, Bataillard M, Ozsancak C, Beauvais K, Auzou P, Amevigbe J, Vuillemet F, Dugay-Arentz MH, Carelli G, Martinez M, Maillet-Vioud M, Escaillas JP, Chapuis S, Tardy J, Manchon E, Varnet O, Kim YJ, Chang Y, Song TJ, Kim JS, Han JH, Noh KC, Lee EJ, Kang DW, Kwon SU, Kwon B, Park S, Lee D, Kwon HS, Jeong D, Lee M, Kim J, Lee H, Nam HJ, Lee SH, Kim BJ, Cha JK, Kim D, Kim RY, Sohn SW, Shim DH, Lee H, Nah HW, Sung SM, Lee KB, Lee JY, Yoon JE, Kim EG, Seo JH, Kim YW, Hwang Y, Park MS, Kim JT, Choi KH, Nam HS, Heo JH, Kim YD, Hwang IG, Park HJ, Kim KS, Baek JH, Song DB, Yoo JS, Park JM, Kwon O, Lee WW, Lee JJ, Kang K, Kim BK, Lim JS, Oh MS, Yu KH, Hong B, Jang M, Jang S, Jin JE, Kim J, Jeong HS, Hong KS, Park HK, Cho YJ, Bang OY, Seo WK, Chung J.

Author information

1
From the Department of Neurology and Stroke Center (P.A., J.L., H.C., L.C., C.G., C.H., P.C.L., E.M., P.-J.T.) and the Department of Cardiology (J.A., G.D., P.G.S.), Assistance Publique-Hôpitaux de Paris (APHP), Bichat Hospital, Laboratory for Vascular Translational Science, INSERM Unité 1148, Département Hospitalo Universitaire-Fibrose Inflammation Remodelage, and the Department of Cardiology, Cochin Hospital (O.V.), University of Paris, the Department of Neurology, Foch Hospital (B.L.), Urgences Cerebrovasculaires (Y.S.), Centre de Pharmacoépidémiologie de l'APHP (N.Y.), and the Department of Endocrinology (E.B.), Hôpital de la Pitié-Salpêtrière, the Department of Biostatistics, APHP, Université Paris Diderot, Sorbonne Paris Cité, Fernand Widal Hospital (É.V.), and the Department of Endocrinology, Sorbonne University (E.B.), Paris, Équipe d'Accueil EA2694, Santé Publique: Epidémiologie et Qualité des Soins (J.L.), and the Department of Neurology, Stroke Unit, University of Lille, Centre Hospitalier Universitaire (CHU) de Lille (D.L.), Lille, the Department of Neurology, University Hospital of Dijon, University of Burgundy, Dijon (Y.B., M.G.), the Stroke Unit, Pasteur Hospital, Nice (M.-H.M.), Hospices Civils de Lyon, Department of Neurology and Stroke Center, Lyon University, Lyon (N.N.), the Department of Neurology, Versailles University Hospital, Versailles (F.P.), the Department of Vascular Neurology, Pellegrin Tripode Hospital, University of Bordeaux, Bordeaux (I.S.), and the Department of Neurology, Université Caen Normandie, CHU Caen Normandie, INSERM Unité 1237, Cyceron, Caen (E.T.) - all in France; Asan Medical Center (J.S.K.), the Department of Neurology, Eunpyeong St. Mary's Hospital, Catholic University of Korea (Y.-J.K.), and the Department of Neurology, Soonchunhyang University College of Medicine (K.-B.L.), Seoul, Dong-a University Hospital (J.-K.C.) and the Department of Neurology and Stroke Center, Pusan National University Hospital (S.M.S.), Busan, and the Department of Neurology, Hallym University Sacred Heart Hospital, Anyang (B.-C.L.) - all in South Korea; and the National Heart and Lung Institute-Imperial College and the Institute of Cardiovascular Medicine and Science-Royal Brompton Hospital, London (P.G.S.).

Abstract

BACKGROUND:

The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied.

METHODS:

In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes.

RESULTS:

A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups.

CONCLUSIONS:

After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).

Comment in

PMID:
31738483
DOI:
10.1056/NEJMoa1910355

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