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Background <p>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> Methods <p>A total of 320 patients undergoing elective first-time OPCABG surgery and receiving 100&#xa0;mg/day oral aspirin and 75&#xa0;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, <i>n</i> = 163), IM group (CYP2C19 1*2 or 1*3 <i>n</i> = 112), and PM group (CYP2C19 2*2 or 2*3, <i>n</i> = 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; <i>P</i> = 0.0076) and 57.8% in the PM group ([HR] versus NM group, 3.363; 95% CI, 1.753 to 6.499; <i>P</i> &lt; 0.0001). Adenosine diphosphate-stimulated platelet aggregation (17.8% ± 4.4% vs. 27.8% ± 4.3% vs. 37.2% ± 5.8%, <i>F</i> = 367.594, <i>P</i> &lt; 0.001), inflammatory cytokines (interleukin-6, 43.5 ± 11.5&#xa0;pg/ml vs. 46.8 ± 11.8&#xa0;pg/ml vs. 51.2 ± 11.4&#xa0;pg/ml, <i>F</i> = 8.471, <i>P</i> &lt; 0.001), and prothrombotic effect (D-dimer, 2.1 ± 0.6&#xa0;ng/ml vs. 2.4 ± 0.7&#xa0;ng/ml vs. 3.2 ± 1.3&#xa0;ng/ml, <i>F</i> = 37.61, <i>P</i> &lt; 0.001) at 5&#xa0;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%], <i>P</i> &lt; 0.001), and postoperative hospital stay (9.9 ± 1.6&#xa0;days vs. 10.4 ± 1.7&#xa0;days vs. 10.8 ± 1.7&#xa0;days, <i>P</i> = 0.004) were notably lower in the NM group compared to the IM group and PM group.</p> Conclusions <p>The weaker CYP2C19 metabolizer&#xa0;phenotype was at the risk of developing POAF after OPCABG surgery with oral clopidogrel regimen.</p> Graphical Abstract <p>The CYP2C19 metabolism phenotype was associated with a differential POAF incidence and burden, platelet aggregability, and inflammatory and prothrombotic responses after OPCABG at the same oral clopidogrel regimen.</p> <p></p>

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New-onset postoperative atrial fibrillation and burden imposed by CYP2C19 metabolizer phenotype on clopidogrel in off-pump coronary artery bypass: a retrospective cohort study

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  • 发表日期：

    2025年10月2日

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  • Qin Jiang,
  • Yalu Yu,
  • Keli Huang,
  • Jiurong Huang,
  • Neng Wang,
  • Shengshou Hu

摘要

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.

Graphical Abstract

The CYP2C19 metabolism phenotype was associated with a differential POAF incidence and burden, platelet aggregability, and inflammatory and prothrombotic responses after OPCABG at the same oral clopidogrel regimen.