Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial

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• 作者：Alain Cariou ; MD^a ; ^b ; ^c ; ^{alain.cariou@aphp.fr" class="auth_mail" title="E-mail the corresponding author} ; Nicolas Deye ; MD^d ; Benoî ; t Vivien ; MD^b ; ^e ; Olivier Richard ; MD^f ; Nicolas Pichon ; MD^g ; Angè ; le Bourg ; MD^h ; Loï ; c Huet ; MDⁱ ; Clé ; ment Buleon ; MD^j ; Jé ; rô ; me Frey ; MD^k ; Pierre Asfar ; MD^l ; Sté ; phane Legriel ; MD^m ; Sophie Narcisse ; MDⁿ ; Armelle Mathonnet ; MD^o ; Auré ; lie Cravoisy ; MD^p ; Pierre-Franç ; ois Dequin ; MD^q ; Eric Wiel ; MD^r ; Keyvan Razazi ; MD^s ; Cé ; dric Daubin ; MD^t ; Antoine Kimmoun ; MD^u ; Lionel Lamhaut ; MD^c ; ^e ; ^v ; Jean-Sé ; bastien Marx ; MD^e ; Didier Payen de la Garanderie ; MD^w ; Patrick Ecollan ; MD^x ; Alain Combes ; MD^y ; Christian Spaulding ; MD^b ; ^c ; ^z ; Florence Barat ; PharmD^aa ; Myriam Ben Boutieb ; MD^bb ; Joë ; l Coste ; MD^b ; ^bb ; Jean-Daniel Chiche ; MD^a ; ^b ; Fré ; dé ; ric Pè ; ne ; MD^a ; ^b ; Jean-Paul Mira ; MD^a ; ^b ; Jean-Marc Treluyer ; MD^b ; ^cc ; Olivier Hermine ; MD^b ; ^dd ; Pierre Carli ; MD^b ; ^e ; for the Epo-ACR-02 Study Group
• 关键词：brain ischemia ; cardiopulmonary resuscitation ; neuroprotection ; reperfusion injury ; thrombosis
• 刊名：Journal of the American College of Cardiology
• 出版年：2016
• 出版时间：5 July 2016
• 年：2016
• 卷：68
• 期：1
• 页码：40-49
• 全文大小：508 K

文摘

Preliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs.

Objectives

The authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial.

Methods

The authors performed a multicenter, single-blind, randomized controlled trial. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible. In the intervention group, patients received 5 intravenous injections spaced 12 h apart during the first 48 h (40,000 units each, resulting in a maximal dose of 200,000 total units), started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients in each group reaching level 1 on the Cerebral Performance Category (CPC) scale (survival with no or minor neurological sequelae) at day 60. Secondary endpoints included all-cause mortality rate, distribution of patients in CPC levels at different time points, and side effects.

Results

In total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p = 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p = 0.01).

Conclusions

In patients resuscitated from an OHCA of presumed cardiac cause, early administration of erythropoietin plus standard therapy did not confer a benefit, and was associated with a higher complication rate. (High Dose of Erythropoietin Analogue After Cardiac Arrest [Epo-ACR-02]; NCT00999583)