Risk Assessment And Antiplatelet Therapy Strategies In Patients Undergoing Percutaneous Coronary Intervention Study

Objective: The present study intended to investigate the potent methods to risk assessment for ischemic and/or bleeding events in patients undergoing percutaneous coronary intervention(PCI),subsequently to evaluate the effectiveness of antiplatelet therapy strategies according to the risk prediction models.Methods:There 3 section in the study.(1)The association between trajectories of biomarkers during hospitalization and clinical prognosis: Coronary Artery Disease and Creative Antithrombotic Clinical Research Collaboration(CARDIACARE)is a cardiovascular disease data platform characterized by automatic data acquisition of artificial intelligence.Based on the CARDIACARE platform,the study was enrolled 31121 acute coronary syndrome(ACS)patients undergoing PCI and survived until hospital discharge in the General Hospital of Northern Theater Command from January 2012 to December 2020.Using the group-based trajectory modeling(GBTM),we analyzed the biomarkers,including hemoglobin,estimating Glomerular Filtration Rate(e GFR),plasma potassium,arachidonic acid(AA)and adenosine diphosphate(ADP)induced platelet aggregation rate,and high sensitivity Troponin T(hs-Tn T).Subsequently,we evaluate the association between trajectories and prognosis.The primary outcomes were12-month ischemic events,a composite of cardiac death,myocardial infarction(MI),and/or stroke;Academic Research Consortium(BARC)type 2,3,5 and 3,5 bleeding at12-month after discharge.(2)The predictive value of multiple risk scores combined to assess the risk of ischemic events: The study was a secondary analysis of I-LOVE-IT 2 trial.The enrolled patients were calculated 4 risk scores,including discharged GRACE(Global Registry of Acute Coronary Events),baseline SYNTAX(Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery),ACEF(Age,Creatinine,and Ejection Fraction),and residual SYNTAX score.Subsequently,the patients were divided into 4groups according to the number that met the threshold of each scores,including discharged GRACE score ≥88,ACEF ≥1.0225,baseline SYNTAX score ≥13,and residual SYNTAX score >0.The primary outcome was ischemic events at 48 months after procedure,a composite of cardiac death,MI,stroke,and/or definite or probable stent thrombosis.(3)Impact of different antiplatelet strategies on clinical prognosis after GRACE score risk stratification: A total of 19704 patients discharged alive post-ACS who underwent PCI and received ticagrelor or clopidogrel between March 2016 and March2019 were included in the study.The patients were divided into 2 groups according to the threshold of discharged GRACE score with 88.Subsequently,we evaluated the effectiveness and safety of clopidogrel-based and ticagrelor-based dual antiplatelet therapy.The definition of primary and secondary outcomes were same with section 1.Results:(1)The association between trajectories of biomarkers during hospitalization and clinical prognosis: The standardized key elements of CARDIACARE comprised 7tables in the documents,including demographic and admission information,medical history and risk factors,clinical presentations and diagnosis,diagnostic and laboratory tests,interventional diagnosis and treatment,pharmacological therapy,clinical outcomes.Currently,more than 270 elements had been developed.After algorithm optimization,the accuracy of these elements could more than 90-95% by manual verification.Meanwhile,there was strong or modest agreement between CARIDACARE platform and a randomized controlled trial with manual entry and verification for demographics,medical history and risk factors,procedural characteristics.A total of 31121 ACS patients undergoing PCI were enrolled in our study.1)The hemoglobin of ACS patients underwent PCI is usually stable during hospitalization with three trajectories.The patients with hemoglobin below the normal range were associated with a higher risk of ischemic events(hazard ratio [HR]: 1.70,95% confidence interval [CI],1.20-2.42),all-cause mortality(HR: 2.55,95%CI,1.71-3.81)and BARC type 3,5 bleeding(HR: 2.19,95%CI,1.37-3.49)at 12 months compared with the normal range.2)The e GFR of ACS patients underwent PCI is usually stable during hospitalization with three trajectories.Comparing with patients with normal and higher value of e GFR,the group with e GFR below normal range had a higher risk of 12-month ischemic events(HR: 1.66,95%CI,1.22-2.25),all-cause mortality(HR: 2.41,95%CI,1.71-3.40),BARC type 2,3,5 bleeding(HR: 1.30,95%CI,1.04-1.63),and BARC type 3,5 bleeding(HR: 1.72,95%CI,1.16-2.56).3)Of all patients,4.5% had a large fluctuation at hospitalization.Compared with patients with normal range,the patients with large fluctuation or high-normal range had a higher risk of 12-month ischemic events(HR: 1.72,95%CI,1.28-2.31 and HR: 1.58,95%CI,1.17-2.13)and all-cause death(HR: 1.97,95%CI,1.42-2.74 and HR: 2.04,95%CI,1.49-2.79).4)There were 3 trajectories of AA induced platelet aggregation rate in ACS patients treated with PCI during hospitalization,including persistently low rate,persistently high rate,and gradual decline.Compared with patients with persistently low rate,the persistently high-rate group was associated with higher rate of 12-month ischemic events(HR: 2.13,95CI%,1.13-3.99)and all-cause death(HR: 2.42,95CI%,1.26-4.67).5)There were 3 trajectories of ADP induced platelet aggregation rate in ACS patients treated with clopidogrel during hospitalization,including persistently low rate,persistently high rate,and gradual decline.There were 3 trajectories of ADP induced platelet aggregation rate in ACS patients treated with ticagrelor during hospitalization,including persistently low rate,gradual decline from high rate and moderate rate.There were 3 trajectories of ADP induced platelet aggregation rate in ACS patients switched clopidogrel to ticagrelor during hospitalization,including persistently low rate and gradual decline.However,there was no significant difference between different trajectories.6)There were 3 trajectories of hs-Tn T in ACS patients treated with PCI during hospitalization,including persistently normal range,gradual decline to normal range,gradual decline with above normal range persistently.The patients with above the normal range had higher incidences of ischemic events(HR;1.89,95%CI,1.28-2.79)and all-cause death(HR: 2.11,95%CI,1.37-3.24)at 12 months.(2)The predictive value of multiple risk scores combined to assess the risk of ischemic events: A total of 2207 CAD patients with stent implantation were analyzed.With the cumulated number of risk scores,the 48-month ischemic events had a significant increasing trend from 6.61% to 16.93%(P for trend<0.001).There were similar increasing trend in cardiac death(from 1.36% to 3.15%),MI(from 3.31% to9.84%),stroke(from 3.31% to 6.10%),and definite/possible stent thrombotic(from0.58% to 1.97%)(All P value for trend <0.001).Compared with single risk score,SYNTAX,residual SYNTAX,ACEF,and GRACE score,the net reclassification index had a significant improvement to predict 48-month ischemic events,with 12.5%(5.3–20.0%),9.4%(2.0–16.8%),12.1%(4.5–19.7%),and 10.7%(3.3–18.1%),respectively.(3)Impact of different antiplatelet strategies on clinical prognosis after GRACE score risk stratification: Of the cohort,ticagrelor group comprised 6432(32.6%)patients and the clopidogrel group comprised 13272(67.4%)patients.Over the follow-up period,a significant reduction in the incidence of ischemic events(1.69% vs.2.46%)and all-cause mortality(1.20% vs.1.75%)in ticagrelor-treatment patients with excessive risk of BARC 2,3,5(4.18% vs.3.32%)and 3,5 bleeding(2.46% vs.1.96%)(All P value<0.05).Among low-risk patients according to GRACE score,ticagrelor use,compared with clopidogrel,was not associated with ischemic events(HR: 0.82,95% CI,0.57-1.17)and all-cause mortality(HR: 1.11,95%CI,0.71-1.73)benefit with excessive risk of bleeding complications(HR: 1.59,95%CI,1.25-2.00 for BARC type 2,3,5bleeding and HR: 1.59,95%CI,1.16-2.17 for BARC type 3,5 bleeding).The risk of ischemic events(HR: 0.60,95%CI,0.41-0.89)and all-cause mortality(HR: 0.53,95%CI,0.34-0.84)were lower in the intermediate-to high-risk patients treated with ticagrelor than those treated with clopidogrel,without significant difference in bleeding risk(HR: 0.96,95%CI,0.70-1.32 for BARC type 2 to 5 bleeding and HR: 1.11,95%CI,0.75-1.65 for BARC type 3 to 5 bleeding).Conclusion: Using the trajectories of biomarkers and multiple risk scores model could improve the predicted value of ischemic and/or bleeding risk in patients underwent PCI.The strategies based on GRACE score risk stratification could support to identify patients who will derive benefit from corresponding individualized antiplatelet strategies.