目的:评价在单纯体外循环冠状动脉旁路移植术(CABG)前P2Y12受体抑制剂停药期较短与严重出血和缺血事件发生率之间的关系。该领域缺乏随机对照试验。
方法:我们搜索了PUBMED,Embase和其他适合研究的数据库,包括接受P2Y12受体抑制剂的患者,接受分离的CABG,并报告2013年至2024年3月的出血和术后缺血事件。主要结局是出血学术研究联盟4型(BARC-4)出血的发生率,定义为以下任何一种:围手术期颅内出血,再次手术出血,输注≥5个单位的红细胞,胸管输出≥2升。根据学术研究联盟2共识文件,次要结果是术后缺血事件。将每个观察性试验提供的患者水平数据合成为单个数据集,并使用两阶段IPD-MA进行分析。
结果:对来自7项观察性研究的4,837例患者的个体数据进行了综合。BARC-4放气,30天死亡率,术后缺血事件发生率为20%,2.6%,5.2%的患者。调整EuroSCOREII和体外循环时间后,符合指南的停药与服用氯吡格雷患者BARC-4出血风险降低相关(调整后比值比[OR]0.48,95%置信区间(CI)0.28-0.81,P=0.006),服用替格瑞洛患者风险降低趋势相关(调整后OR0.48,95%CI0.22-1.05;P=0.067).遵循指南的停药与30天死亡风险无显著相关(氯吡格雷:调整OR0.70,95%CI0.30-1.61;替格瑞洛:调整OR0.89,95%CI0.37-2.18),但氯吡格雷组患者术后缺血事件风险降低(氯吡格雷:调整OR,95%CI0.30-0.82;替格瑞洛:调整OR0.78,1.37)。BARC-4出血与30天死亡风险相关(校正OR4.76,95%CI2.67-8.47;P<0.001)。
结论:符合指南的术前停药替格瑞洛和氯吡格雷与经EuroSCOREⅡ和体外循环时间校正后的BARC-4出血风险降低50%相关,但与30天死亡率或术后缺血事件风险增加无关。
OBJECTIVE: To evaluate the association between guideline-conforming as compared to shorter than recommended withdrawal period of P2Y12 receptor inhibitors prior to isolated on-pump coronary artery bypass grafting (CABG) and the incidence of severe bleeding and ischaemic events. Randomized controlled trials are lacking in this field.
METHODS: We searched PUBMED, Embase and other suitable databases for studies including patients on P2Y12 receptor inhibitors undergoing isolated CABG and reporting bleeding and postoperative ischaemic events from 2013 to March 2024. The primary outcome was incidence of Bleeding Academic Research Consortium type 4 (BARC-4) bleeding defined as any of the following: perioperative intracranial bleeding, reoperation for bleeding, transfusion of ≥5 units of red blood cells, chest tube output of ≥2 l. The secondary outcome was postoperative ischaemic events according to the Academic Research Consortium 2 Consensus Document. Patient-level data provided by each observational trial were synthesized into a single dataset and analysed using a 2-stage IPD-MA.
RESULTS: Individual data of 4837 patients from 7 observational studies were synthesized. BARC-4 bleeding, 30-day mortality and postoperative ischaemic events occurred in 20%, 2.6% and 5.2% of patients. After adjusting for EuroSCORE II and cardiopulmonary bypass time, guideline-conforming withdrawal was associated with decreased BARC-4 bleeding risk in patients on clopidogrel [adjusted odds ratio (OR) 0.48; 95% confidence intervals (CI) 0.28-0.81; P = 0.006] and a trend towards decreased risk in patients on ticagrelor (adjusted OR 0.48; 95% CI 0.22-1.05; P = 0.067). Guideline-conforming withdrawal was not significantly associated with 30-day mortality risk (clopidogrel: adjusted OR 0.70; 95% CI 0.30-1.61; ticagrelor: adjusted OR 0.89; 95% CI 0.37-2.18) but with decreased risk of postoperative ischaemic events in patients on clopidogrel (clopidogrel: adjusted OR 0.50; 95% CI 0.30-0.82; ticagrelor: adjusted OR 0.78; 95% CI 0.45-1.37). BARC-4 bleeding was associated with 30-day mortality risk (adjusted OR 4.76; 95% CI 2.67-8.47; P < 0.001).
CONCLUSIONS: Guideline-conforming preoperative withdrawal of ticagrelor and clopidogrel was associated with a 50% reduced BARC-4 bleeding risk when corrected for EuroSCORE II and cardiopulmonary bypass time but was not associated with increased risk of 30-day mortality or postoperative ischaemic events.