Perioperative Assessment Of The Relationship Of Diabetes Mellitus To On-clopidogrel Treatment Platelet Reactivity Monitoring By Thrombelastograph During Percutaneous Coronary Intervention

Objective：Several lines of evidence from basic research and clinical studiesunderline the central role of platelet activation in the pathogenesis of acutecoronary syndromes (ACS). Percutaneous coronary intervention (PCI), themain interventional treatment in ACS patients, constitutes a powerfulthrombogenic stimulus in itself. The P2Y12receptor is a Gi-coupledadenosine diphosphate (ADP) receptor, which plays a pivotal role in plateletactivation and aggregation through a complex cascade of actions. It istherefore obvious why the P2Y12receptor has become a molecular target inthe development of antiplatelet drugs administered to ACS/PCI patients. Overthe last decade, dual antiplatelet therapy has been the mainstay of themanagement of Acute Coronary Syndrome, with clopidogrel therapyproviding clear benefits over aspirin monotherapy and becoming the agent ofchoice for the prevention of stent thrombosis. A poor response of the plateletsto clopidogrel, called High Residual Platelet Reactivity (HRPR), has beenincriminated to account for recurrent ischemic events. Clopidogrel metabolismis highly variable, and genetics, comorbidities and drug interactions can affectit. High-risk subpopulations like ST elevation myocardial infarction (STEMI),diabetes, chronic kidney disease (CKD), elderly, and low body weight (LBW)patients have been identified.Intense research efforts have focused on linking HPR with clinicaloutcomes and, most importantly, on using platelet function testing (PFT) as aguide to tailored antiplatelet treatment. The relationship of periproceduralplatelet reactivity to diabetes mellitus and its variation taking clopidogrel andundergoing percutaneous coronary intervention (PCI) are unclear. The purpose of the present study was to prospectively evaluate the impactof coronary interventions on periprocedural variations of PR and to investigatewhether HPR measured by thrombelastography correlates with diabetesmellitus (DM) in patients receiving clopidogrel and undergoing PCI.Methods：A total of90patients undergoing PCI who were admitted to the SecondHospital of Hebei Medical University during2013.11to2014.02for acutecoronary syndrome and with both aspirin and clopidogrel pre-treatment(100mg daily and75mg daily respectively for more than5days or both300mg loading dose6h before procedural) were prospectively enrolled.Platelet function analysis was performed using the thrombelastography. PRwas assessed prior to,7days after the procedure. Baseline and residual plateletreactivity were described as MAthrombinand MAADP, respectively. High plateletreactivity (HPR) after clopidogrel was defined as percentage clottinginhibition (%CI) to ADP<30%. Major adverse cardiac events (MACE) weredefined as cardiac death, myocardial infarction (MI), stroke or stentthrombosis. Complete data of patients enrolled were required duringhospitalization.Continuous variables are expressed as mean±SD, and categoricalvariables are reported as frequencies and percentages. Normality was tested bythe Kolmogorov-Smirnov test. Continuous variables were compared by t-testfor normally distributed values; otherwise Mann-Whitney U-test was used.Comparisons between categorical variables were made using Fisher’s exacttest when the expected frequency was <5; otherwise chi-square test wasapplied. Statistical analysis was performed using SPSS19.0. Statisticssignificance was accepted at a P value of <0.05.Results：1There was no significant difference among baseline characteristics inpatients with versus without diabetes mellitus（P>0.05）.2Neither procedural characteristics nor7days major cardiac adverseevents had statistically significant difference in two groups（P>0.05）. 3Both baseline and residual of on-treatment platelet reactivity increasedafter PCI, the impact of coronary interventions on periprocedural variations ofPR lasted for more than7days.MAthrombin（mm）63.24±5.89vs.64.54±6.04，P=0.004；MAADP（mm）35.55±15.43vs.48.90±12.18，P=0.000。4Patients with DM had significantly higher not only platelet reactivitybaseline but also residual platelet reactivity before PCI compared tonondiabetics.①MAthrombin（mm）：Before PCI66.57±3.76vs.61.11±5.99， P=0.004； After PCI68.30±4.30vs.62.14±5.79，P=0.014；②MAADP（mm）：Before PCI36.83±16.56vs.30.62±14.50，P=0.048；After PCI53.95±8.72vs.45.69±13.02，P=0.001；③Periprocedrual variation of platelet reactivity bought by percutaneouscoronary intervention was more significant in diabetics patients because oflarger changes on both baseline and residual platelet reactivity.ΔMAthrombin（mm）1.73±1.72vs.1.03±1.42，P=0.006；ΔMAADP（mm）17.63±11.35vs.15.07±8.32，P=0.005；④HPR was more frequently observed in diabetics before and after PCI.Before PCI：40%vs.18.2%，P=0.029；After PCI：71.4%vs.49.1%，P=0.049。Conclusion：Despite dual antiplatelet therapy, PCI affected platelet function andpatients with DM have higher levels of platelet reactivity baseline, residualplatelet reactivity and peripercedural variation of PR, which means higher riskfor major adverse cardiac events. More effective platelet inhibition strategiesin complex interventional procedures or in patients with DM are advocated.TEG is a plausible platelet function test that can be used to deliver point ofcare personalised antiplatelet therapy.