Qin Jiang, Yalu Yu, Keli Huang, Jiurong Huang, Neng Wang, Shengshou Hu
{"title":"非体外循环冠状动脉搭桥术中新发房颤及CYP2C19代谢物表型对氯吡格雷负担的回顾性队列研究","authors":"Qin Jiang, Yalu Yu, Keli Huang, Jiurong Huang, Neng Wang, Shengshou Hu","doi":"10.1186/s13741-025-00592-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of new-onset postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (OPCABG) surgery remains to be partly known. The association between clopidogrel metabolizer phenotype and the occurrence of POAF was investigated.</p><p><strong>Methods: </strong>A total of 320 patients undergoing elective first-time OPCABG surgery and receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel was reviewed from May 2017 to November 2023. These patients were categorized as normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM) according to cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotyping. The incidences of POAF in the first week were compared using the log-rank test for cumulative risk. Platelet aggregability, inflammatory indexes, prothrombotic effect, and POAF burden were analyzed. Three phenotype categories were divided by genotyping as NM group (CYP2C19 1*1, n = 163), IM group (CYP2C19 1*2 or 1*3 n = 112), and PM group (CYP2C19 2*2 or 2*3, n = 45). The incidence of POAF after OPCABG was 20.9% in the NM group, contrasting with 35.7% in the IM group (hazard ratio [HR] versus NM group, 1.843; 95% confidence interval [CI], 1.155 to 2.940; P = 0.0076) and 57.8% in the PM group ([HR] versus NM group, 3.363; 95% CI, 1.753 to 6.499; P < 0.0001). Adenosine diphosphate-stimulated platelet aggregation (17.8% ± 4.4% vs. 27.8% ± 4.3% vs. 37.2% ± 5.8%, F = 367.594, P < 0.001), inflammatory cytokines (interleukin-6, 43.5 ± 11.5 pg/ml vs. 46.8 ± 11.8 pg/ml vs. 51.2 ± 11.4 pg/ml, F = 8.471, P < 0.001), and prothrombotic effect (D-dimer, 2.1 ± 0.6 ng/ml vs. 2.4 ± 0.7 ng/ml vs. 3.2 ± 1.3 ng/ml, F = 37.61, P < 0.001) at 5 days after OPCABG, POAF burden (3.0% [1.2%, 6.1%] vs. 4.8% [2.4%, 11.9%] vs. 8.9% [4.8%, 17.4%], P < 0.001), and postoperative hospital stay (9.9 ± 1.6 days vs. 10.4 ± 1.7 days vs. 10.8 ± 1.7 days, P = 0.004) were notably lower in the NM group compared to the IM group and PM group.</p><p><strong>Conclusions: </strong>The weaker CYP2C19 metabolizer phenotype was at the risk of developing POAF after OPCABG surgery with oral clopidogrel regimen.</p>","PeriodicalId":19764,"journal":{"name":"Perioperative Medicine","volume":"14 1","pages":"103"},"PeriodicalIF":2.1000,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492532/pdf/","citationCount":"0","resultStr":"{\"title\":\"New-onset postoperative atrial fibrillation and burden imposed by CYP2C19 metabolizer phenotype on clopidogrel in off-pump coronary artery bypass: a retrospective cohort study.\",\"authors\":\"Qin Jiang, Yalu Yu, Keli Huang, Jiurong Huang, Neng Wang, Shengshou Hu\",\"doi\":\"10.1186/s13741-025-00592-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The pathogenesis of new-onset postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (OPCABG) surgery remains to be partly known. The association between clopidogrel metabolizer phenotype and the occurrence of POAF was investigated.</p><p><strong>Methods: </strong>A total of 320 patients undergoing elective first-time OPCABG surgery and receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel was reviewed from May 2017 to November 2023. These patients were categorized as normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM) according to cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotyping. The incidences of POAF in the first week were compared using the log-rank test for cumulative risk. Platelet aggregability, inflammatory indexes, prothrombotic effect, and POAF burden were analyzed. Three phenotype categories were divided by genotyping as NM group (CYP2C19 1*1, n = 163), IM group (CYP2C19 1*2 or 1*3 n = 112), and PM group (CYP2C19 2*2 or 2*3, n = 45). The incidence of POAF after OPCABG was 20.9% in the NM group, contrasting with 35.7% in the IM group (hazard ratio [HR] versus NM group, 1.843; 95% confidence interval [CI], 1.155 to 2.940; P = 0.0076) and 57.8% in the PM group ([HR] versus NM group, 3.363; 95% CI, 1.753 to 6.499; P < 0.0001). Adenosine diphosphate-stimulated platelet aggregation (17.8% ± 4.4% vs. 27.8% ± 4.3% vs. 37.2% ± 5.8%, F = 367.594, P < 0.001), inflammatory cytokines (interleukin-6, 43.5 ± 11.5 pg/ml vs. 46.8 ± 11.8 pg/ml vs. 51.2 ± 11.4 pg/ml, F = 8.471, P < 0.001), and prothrombotic effect (D-dimer, 2.1 ± 0.6 ng/ml vs. 2.4 ± 0.7 ng/ml vs. 3.2 ± 1.3 ng/ml, F = 37.61, P < 0.001) at 5 days after OPCABG, POAF burden (3.0% [1.2%, 6.1%] vs. 4.8% [2.4%, 11.9%] vs. 8.9% [4.8%, 17.4%], P < 0.001), and postoperative hospital stay (9.9 ± 1.6 days vs. 10.4 ± 1.7 days vs. 10.8 ± 1.7 days, P = 0.004) were notably lower in the NM group compared to the IM group and PM group.</p><p><strong>Conclusions: </strong>The weaker CYP2C19 metabolizer phenotype was at the risk of developing POAF after OPCABG surgery with oral clopidogrel regimen.</p>\",\"PeriodicalId\":19764,\"journal\":{\"name\":\"Perioperative Medicine\",\"volume\":\"14 1\",\"pages\":\"103\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492532/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Perioperative Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13741-025-00592-y\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ANESTHESIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Perioperative Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13741-025-00592-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ANESTHESIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：非体外循环冠状动脉旁路移植术（OPCABG）术后新发心房颤动（POAF）的发病机制尚不完全清楚。研究氯吡格雷代谢物表型与POAF发生的关系。方法：对2017年5月至2023年11月期间接受择期首次OPCABG手术并口服阿司匹林100 mg/d和口服氯吡格雷75 mg/d的320例患者进行回顾性分析。根据细胞色素P450、家族2、亚家族C、多肽19 （CYP2C19）基因分型将患者分为正常代谢者（NM）、中间代谢者（IM）和不良代谢者（PM）。采用累积风险的log-rank检验比较第一周的POAF发生率。分析血小板聚集性、炎症指标、血栓前作用和POAF负担。基因分型将表型分为NM组（CYP2C19 1*1, n = 163）、IM组（CYP2C19 1*2或1*3，n = 112）和PM组（CYP2C19 2*2或2*3，n = 45）。NM组OPCABG术后POAF发生率为20.9%，IM组为35.7%（风险比[HR] vs NM组，1.843；95%可信区间[CI]， 1.155 ~ 2.940; P = 0.0076）， PM组为57.8% ([HR] vs NM组，3.363;95% CI, 1.753 ~ 6.499； P结论：口服氯吡格雷方案OPCABG术后CYP2C19代谢产物表型较弱者存在发生POAF的风险。
New-onset postoperative atrial fibrillation and burden imposed by CYP2C19 metabolizer phenotype on clopidogrel in off-pump coronary artery bypass: a retrospective cohort study.
Background: The pathogenesis of new-onset postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (OPCABG) surgery remains to be partly known. The association between clopidogrel metabolizer phenotype and the occurrence of POAF was investigated.
Methods: A total of 320 patients undergoing elective first-time OPCABG surgery and receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel was reviewed from May 2017 to November 2023. These patients were categorized as normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM) according to cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotyping. The incidences of POAF in the first week were compared using the log-rank test for cumulative risk. Platelet aggregability, inflammatory indexes, prothrombotic effect, and POAF burden were analyzed. Three phenotype categories were divided by genotyping as NM group (CYP2C19 1*1, n = 163), IM group (CYP2C19 1*2 or 1*3 n = 112), and PM group (CYP2C19 2*2 or 2*3, n = 45). The incidence of POAF after OPCABG was 20.9% in the NM group, contrasting with 35.7% in the IM group (hazard ratio [HR] versus NM group, 1.843; 95% confidence interval [CI], 1.155 to 2.940; P = 0.0076) and 57.8% in the PM group ([HR] versus NM group, 3.363; 95% CI, 1.753 to 6.499; P < 0.0001). Adenosine diphosphate-stimulated platelet aggregation (17.8% ± 4.4% vs. 27.8% ± 4.3% vs. 37.2% ± 5.8%, F = 367.594, P < 0.001), inflammatory cytokines (interleukin-6, 43.5 ± 11.5 pg/ml vs. 46.8 ± 11.8 pg/ml vs. 51.2 ± 11.4 pg/ml, F = 8.471, P < 0.001), and prothrombotic effect (D-dimer, 2.1 ± 0.6 ng/ml vs. 2.4 ± 0.7 ng/ml vs. 3.2 ± 1.3 ng/ml, F = 37.61, P < 0.001) at 5 days after OPCABG, POAF burden (3.0% [1.2%, 6.1%] vs. 4.8% [2.4%, 11.9%] vs. 8.9% [4.8%, 17.4%], P < 0.001), and postoperative hospital stay (9.9 ± 1.6 days vs. 10.4 ± 1.7 days vs. 10.8 ± 1.7 days, P = 0.004) were notably lower in the NM group compared to the IM group and PM group.
Conclusions: The weaker CYP2C19 metabolizer phenotype was at the risk of developing POAF after OPCABG surgery with oral clopidogrel regimen.
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