法国巴黎皮提耶-萨尔佩特里尔医院Gilles Montalescot团队比较了替卡格雷和氯吡格雷在选择性经皮冠状动脉介入治疗中的应用效果。2020年11月14日，该研究发表在《柳叶刀》杂志上。

经皮冠状动脉介入治疗（PCI）相关的心肌坏死很常见，并且会影响患者的长期预后。与目前推荐的治疗药物氯吡格雷相比，替卡格雷可减少围手术期缺血并发症尚未在择期PCI中进行评估。

为了评估在接受高危择期PCI的稳定型冠心病患者中，替卡格雷在减轻围手术期心肌坏死方面是否优于氯吡格雷，研究组在法国和捷克共和国的49家医院进行了一项临床3b期、随机开放标签试验。2017年1月9日至2020年5月28日，共招募了1910名稳定型冠心病、具有PCI适应症、至少有一项高危临床特征的患者。

将患者随机分组，其中956名接受替卡格雷治疗，954名接受氯吡格雷治疗。主要结局为PCI相关的4型（a或b）心肌梗塞或严重心肌损伤的综合结局，主要安全结局是大出血，均在PCI后48小时内（或较早出院时）进行评估。最终替卡格雷组排除了15例患者，氯吡格雷组排除了12例患者。

在第48小时，替卡格雷组941名患者中有334名（35％）观察到了主要结局，而氯吡格雷组942名患者中有341名（36％），差异不显著。两组间的主要安全结局无显著差异，但替卡格雷组30天时的小出血事件发生率为11%，显著高于氯吡格雷组（8%）。

研究结果表明，替卡格雷在选择性PCI后减少围手术期心肌坏死方面不优于氯吡格雷，虽未引起大出血增加，但30天时增加了小出血率，不值得临床推广。

附：英文原文

Title: Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial

Author: Johanne Silvain, Benoit Lattuca, Farzin Beygui, Grégoire Rangé, Zuzana Motovska, Jean-Guillaume Dillinger, Ziad Boueri, Philippe Brunel, Thibault Lhermusier, Christophe Pouillot, Elisa Larrieu-Ardilouze, Franck Boccara, Jean-Nol Labeque, Paul Guedeney, Mohamad El Kasty, Mikael Laredo, Raphalle Dumaine, Grégory Ducrocq, Jean-Philippe Collet, Guillaume Cayla, Katrien Blanchart, Petr Kala, Eric Vicaut, Gilles Montalescot, Johanne SILVAIN, Jean-Philippe COLLET, Gilles MONTALESCOT, Mathieu KERNEIS, Nassim BRAIK, Olivier BARTHELEMY, Gérard HELFT, Claude LEFEUVRE, Rémi CHOUSSAT, Marie HAUGUEL, Michel ZEITOUNI, Thomas CUISSET, Jean-Louis BONNET, Pierre DEHARO, Benoit LATTUCA, Guillaume CAYLA, Luc CORNILLET, Bertrand LEDERMANN, Clément LONJON, Laurent SCHMUTZ, Grégoire RANGE, Franck ALBERT, Thibault DEMICHELI, Laurent ROUSSEL, Reda BENSAID, Christophe THUAIRE, Jean-Guillaume DILLINGER, Patrick HENRY, Stéphane MANZO-SILBERMAN, Georgios SIDERIS, Damien LOGEART, Vincent SPAGNOLI, Léa CACOUB, Christophe POUILLOT, Jean Richard VI-FANE, Jens GLASENAPP, Karim BOUGRINI, Nicolas COMBARET, Pascal MOTREFF, Géraud SOUTEYRAND, Aimé AMONCHOT, Thomas MOUYEN, Thibault LHERMUSIER, Didier CARRIE, Frédéric BOUISSET, Thomas CHOLLET, Francisco CAMPELO-PARADA, Nicolas DELARCHE, Franois SCHIELE, Mathieu BESUTTI, Marie HAUGUEL-MOREAU, Rami EL MAHMOUD, Christophe CAUSSIN, Mami ZOHEIR, Aurelie VEUGEOIS, Alain DIBIE, Olivier VARENNE, Fabien PICARD, Alexandre LAFONT, Julien ADJEDJ, Philippe DEGRELL, Farzin BEYGUI, Rémi SABATIER, Vincent ROULE, Mathieux BIGNON, Katrien BLANCHART, Pierre ARDOUIN, Adrien LEMAITRE, Clément BRIET, Ziad BOUERI, Pascal GOUBE, Pierre COSTE, Laura CETRAN, Jérme CLERC, Hervé LE BRETON, Dominique BOULMIER, Vincent AUFFRET, Jean-Nol LABEQUE, Jean-Luc BONAS, Jean-Louis GEORGES, Bernard LIVAREK, Elodie BLICQ, Nicolas BARON, Géraldine GIBAULT-GENTY, Yves COTTIN, Isabelle LHUILLIER, Carole RICHARD, Luc LORGIS, Philippe BUFFET, Christian SPAULDING, Nicole KARAM, Etienne PUYMIRAT, Marco MENNUNI, Emmanuel POULIDAKIS, Lionel BONNEVIE, Franck BOCCARA, Marion CHAUVET, Laurie DUFOUR, Yann ANCEDY, Stéphane EDERHY

Issue&Volume: 2020-11-14

Abstract:

Background

Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI.

Methods

The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300–600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290.

Findings

Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80–1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12–2·11; p=0·0070).

Interpretation

Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI.

DOI: 10.1016/S0140-6736(20)32236-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32236-4/fulltext