美国威尔康奈尔医学院Mario Gaudino团队研究了替卡格雷联合抗血小板治疗与冠状动脉搭桥术后静脉移植失败的相关性。这一研究成果于2022年8月9日发表在《美国医学会杂志》上。

冠状动脉搭桥术后替卡格雷加或不加阿司匹林的作用尚不清楚。

为了比较替卡格雷双重抗血小板治疗（DAPT）或替卡格雷单药治疗与阿司匹林治疗冠状动脉搭桥术患者静脉移植失败和出血的风险，研究组在MEDLINE、Embase和Cochrane图书馆等大型数据库中检索从建库到2022年6月1日的相关文献（无语言限制），筛选出比较替卡格雷DAPT或替卡格雷单药治疗与阿司匹林治疗后大隐静脉移植失败率的随机临床试验（RCT），将每个试验提供的个体患者数据合成为组合数据集，以进行独立分析。采用多水平logistic回归模型。

初步分析通过比较替卡格雷DAPT和阿司匹林，评估了随机对照试验中每个移植物大隐静脉移植失败的发生率（主要结局）。次要结局为每位患者大隐静脉移植失败和出血学术研究联合会（BARC）2、3或5型出血事件。补充分析包括比较替卡格雷单药治疗与阿司匹林的随机对照试验。

荟萃分析共包括4项随机对照试验，涉及1316例患者和1668例大隐静脉移植物。在初步分析的871名患者中，435名接受替卡格雷-DAPT治疗（中位年龄为67岁；65名为女性[14.9%]；370名为男性[85.1%]），436名接受阿司匹林治疗（中位年龄为66岁；63名为女性；373名为男性[85.5%]）。

替卡格雷DAPT组中每个移植物大隐静脉移植失败率为11.2%，显著低于阿司匹林组的20%，OR为0.51；每位患者大隐静脉移植失败率为13.2%，显著低于阿司匹林组的23.0%，OR为0.51。替卡格雷DAPT组中BARC 2型、3型或5型出血事件的总发生率为22.1%，显著高于阿司匹林组的8.7%；但两组中BARC 3型或5型出血事件的发生率均为1.8%，组间差异不显著。替卡格雷单药治疗组的大隐静脉移植失败率为19.3%，阿司匹林组为21.7%；BARC 2、3或5型出血事件发生率为8.9%，阿司匹林组为7.3%，组间差异均不显著。

研究结果表明，在接受冠状动脉搭桥手术的患者中，在阿司匹林中加入替卡格雷可显著降低静脉移植失败的风险，但这伴随着临床上重要的出血风险显著增加。

附：英文原文

Title: Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis

Author: Sigrid Sandner, Bjrn Redfors, Dominick J. Angiolillo, Katia Audisio, Stephen E. Fremes, Paul W.A. Janssen, Alexander Kulik, Roxana Mehran, Joyce Peper, Marc Ruel, Jacqueline Saw, Giovanni Jr Soletti, Andrew Starovoytov, Jurrien M. ten Berg, Laura M. Willemsen, Qiang Zhao, Yunpeng Zhu, Mario Gaudino

Issue&Volume: 2022/08/09

Abstract:

Importance  The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear.

Objective  To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery.

Data Sources  MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction.

Study Selection  Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure.

Data Extraction and Synthesis  Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used.

Main Outcomes and Measures  The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin.

Results  A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, 8.7% [95% CI, 13.5% to 3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P<.001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, 9.7% [95% CI, 14.9% to 4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P<.001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P<.001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, 1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P=.99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, 2.6% [95% CI, 9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P=.44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, 2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P=.46).

Conclusions and Relevance  Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.

DOI: 10.1001/jama.2022.11966

Source: https://jamanetwork.com/journals/jama/article-abstract/2795029