Association of CYP2C19 genotypes with postoperative atrial fibrillation after coronary artery bypass surgery.

Publisher: WileyBlackwell Pub Country of Publication: United States NLM ID: 101474067 Publication Model: Print Cited Medium: Internet ISSN: 1752-8062 (Electronic) Linking ISSN: 17528054 NLM ISO Abbreviation: Clin Transl Sci Subsets: MEDLINE

Original Publication: Malden, MA : WileyBlackwell Pub., 2008-

Cytochrome P-450 CYP2C19*/genetics ; Cytochrome P-450 CYP2C19*/metabolism ; Atrial Fibrillation*/etiology ; Atrial Fibrillation*/genetics ; Atrial Fibrillation*/epidemiology ; Coronary Artery Bypass*/adverse effects ; Clopidogrel*/administration & dosage ; Clopidogrel*/adverse effects ; Postoperative Complications*/etiology ; Postoperative Complications*/epidemiology ; Genotype* ; Platelet Aggregation Inhibitors*/administration & dosage ; Platelet Aggregation Inhibitors*/adverse effects ; Platelet Aggregation*/drug effects; Humans ; Male ; Female ; Aged ; Middle Aged ; Incidence ; Aspirin/administration & dosage ; Aspirin/adverse effects

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 CYP2C19*1*1 (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.
(© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

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EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
EC 1.14.14.1 (CYP2C19 protein, human)
A74586SNO7 (Clopidogrel)
0 (Platelet Aggregation Inhibitors)
R16CO5Y76E (Aspirin)

Date Created: 20240615 Date Completed: 20240615 Latest Revision: 20241003

20241003

PMC11178516

10.1111/cts.13862

38877696