Department of Cardiac Surgery, Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Technology, Chengdu, China.
Department of Pharmacy, Sichuan Provincial People's Hospital, Chengdu, China.
Clin Transl Sci. 2024 Jun;17(6):e13862. doi: 10.1111/cts.13862.
This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C1911 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.
这项队列研究旨在评估细胞色素 P450 家族 2 亚家族 C 成员 19(CYP2C19)基因分型、氯吡格雷口服给药后的血小板聚集性与非体外循环冠状动脉旁路移植术(CABG)后术后心房颤动(POAF)的发生之间的关系。2017 年 5 月至 2022 年 11 月,共纳入 258 例择期首次 CABG 手术患者,术后接受 100mg/d 阿司匹林和 75mg/d 氯吡格雷口服。根据 CYP2C19 基因分型对这些患者进行分类。使用多电极聚集仪在 CABG 前、术后 1 天和 5 天以及出院前连续评估血小板聚集性。使用对数秩检验比较 POAF 的发生率。CYP2C19 基因分型导致分类为 CYP2C1911(WT 组,n=123)和 CYP2C19*2 或 *3(LOF 组,n=135)。两组间的基线特征和手术数据无显著差异。LOF 组 CABG 后的 POAF 发生率为 42.2%,而 WT 组为 22.8%(风险比 [HR]:2.061;95%置信区间 [CI]:1.347,3.153;p=0.0013)。与 WT 组相比,LOF 组在 CABG 后 5 天腺苷二磷酸刺激的血小板聚集明显更高(30.4%±6.5%比 17.9%±4.1%,p<0.001),在出院时仍保持类似的较高水平(25.6%±6.1%比 12.2%±3.5%,p<0.001)。CYP2C19 LOF 的存在与 POAF 的发生率较高以及在相同的氯吡格雷方案下 CABG 手术后血小板聚集相对升高相关。