Ticagrelor Versus Clopidogrel for Post-Operative Inflammation and the CD4/CD8 Ratio After CABG: A Propensity-Score-Matched Cohort Study Stratified by Residual LDL-C

Background: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass triggers an intense systemic inflammatory response and a transient depression of T-cell responses, both linked to postoperative complications and infection. Patients remaining above the guideline low-density-lipoprotein cholesterol (LDL-C) target retain residual lipid-related risk, which may coexist with residual inflammatory risk. Therefore, we pre-specified residual LDL-C (≥1.4 mmol/L) as a stratification variable rather than an eligibility criterion. Beyond P2Y12 blockade, ticagrelor exerts adenosine-mediated pleiotropic effects that may modulate inflammation and T-cell function. We aimed to examine whether it differs from clopidogrel in early post-CABG inflammation and the cluster of differentiation 4 (CD4)/CD8 ratio and to what extent any difference is paralleled by concurrently measured platelet inhibition.Methods: In a single-center retrospective cohort undergoing elective isolated on-pump CABG under guideline-directed statin therapy, 1:1 propensity-score matching yielded 258 patients (129 pairs), of whom 179 of 258 (69.4%) had residual high LDL-C (≥1.4 mmol/L). The co-primary outcomes of day-3 C-reactive protein (CRP) and CD4/CD8 ratio were compared using analysis of covariance with adjustment for baseline values and pre-specified covariates. The robustness of the findings was further evaluated using stabilized inverse-probability weighting, cluster-robust inference, E-values, and an exploratory, non-causal decomposition of the between-group difference with respect to adenosine diphosphate (ADP)-induced platelet inhibition.Results: Ticagrelor was associated with lower day-3 CRP (adjusted difference –20.96 mg/L, 95% confidence interval (CI) –27.74 to –14.18, roughly 12% relative reduction) and a higher CD4/CD8 ratio (+0.117, 95% CI 0.058 to 0.175, both p < 0.001). Estimates were robust across weighting, log-scale, and cluster-robust analyses (E-values 3.34 and 2.34). In an exploratory decomposition, the component statistically shared with ADP-induced platelet inhibition corresponded to approximately 34.5% and 41.2% of the respective differences, with the larger part of each difference unexplained by measured platelet reactivity. Because platelet reactivity was measured on days 3–5, that is, concurrently with or after the day-3 outcome, these proportions are descriptive and cannot be interpreted as mediation. Residual LDL-C did not significantly modify the effect.Conclusion: Among statin-treated patients undergoing on-pump CABG, ticagrelor was associated with lower early inflammation and a higher CD4/CD8 ratio than clopidogrel, differences that were only partly paralleled by concurrently measured platelet inhibition. These hypothesis-generating findings warrant confirmation in a randomized trial.