Predictive Value Of Platelet Reactivity Tests For Adverse Events In ACS Patients After Discharge

BackgroundThe prognosis of patients in coronary heart diseases(CHD)is a concerned topic for a long time.A huge argue about the value to predict CHD prognosis or guide changes in anti-platelet drugs of platelet residual reactivity after drug therapies exists.It also has no enough evidences to recommend in population widely.AimsBy testing plural testing points by six methods to measure platelet reactivity.Assessing the testing abilities of various platelet function tests and whether platelet function testing may help in the prognostic improvement in patients with CHD.Moreover,exploring whether the combination of multiple platelet function tests will improve the detection ability of platelet function testing.Methods and findingThis study is a single-center subgroup study of the multi-center,prospective,observational cohort study "PRACTICE,the Platelet reactivity and Clinical Thrombotic Events Study"(clinicaltrials.gov:NCT03525145),including767 patients diagnosed with ACS who were enrolled in the single center of the General Hospital of Northern Theater Command.Using different platelet function tests(LTA、VASP phosphorylation、Verifynow System and PL System)to measure the platelet reactivity after antiplatelet treatment reached a basically steady state(after loading dose 72 hours or maintain unloading for 5 hours)in patients with acute coronary syndrome(ACS).Patients should not measure by only single method.In this study,correlation analysis was used to investigate the correlation between different platelet reactivity tests.Secondly,clopidogrel only group,ticagrelor only group,and P2Y12 drug exchanged group were divided by the in-hospital P2Y12 inhibitor strategies.The platelet reactivity test values between the three groups were compared under different P2Y12 treatment strategies.Finally,the predictive value of every testing method alone or combined with other methods to the occurrence of bleeding events after discharge was evaluated by the receiver operating Curve.Our study enrolled 767 patients from the General Hospital of Northern Theater Command Hospital single-center were included in the PRACTICE study.The average age of the study population was 59 years old,and 74.40%were male.72.10% of the patients admitted were diagnosed with unstable angina pectoris,17.60% were diagnosed with non-ST elevation myocardial infarction,and 10.30% were diagnosed with ST elevation myocardial infarction.75.70% of patients were found to have multi-vessel lesions during PCI,83.50% of patients were found to have at least one of the factors of complex lesion which include long lesions,restenosis lesions,small vessel lesions,bifurcation lesions,CTO lesions,calcification of lesions and pontoon lesions.The average number of complex lesions was 1.17.6 different kinds of platelet reactivity testing methods have included in our study(LTA-AA、LTA-ADP、PL-AA 、 PL-ADP 、 VASP phosphorylation and Verifynow System),with diversification in groundworks or testing points.(1)The measured values of different testing points under the same tool usually have a high correlation.There was a moderate correlation between LTA-AA and LTA-ADP(r=0.456,P<0.001)and a strong correlation between PL-AA and PL-ADP(r=0.638,P<0.001).The results of the same testing point under different tools have a certain correlation as well.There was a weak correlation between the values of LTA-AA and PL-AA(r=0.306,P<0.001)to monitor platelet reactivity to acetyl salicylic acid drugs and a weak correlation between LTA-ADP and PL-ADP for the addition of ADP to monitor platelet reactivity to thiophene pyridine drugs(r=0.305,P<0.001).(2)The study population was divided into three groups who had only used clopidogrel,had only used ticagrelor,and had used two drugs alternately in hospital.There were 371 people in the clopidogrel group,184 people in the ticagrelor group,and 188 people had exchanged drugs.Patients in the clopidogrel only group were generally older(60.89 vs 50.03 vs 57.39,P<0.001)and weighed less(71.29 vs 72.93 vs 74.16,P=0.014).All bleeding events were lower at the first follow-up at 3 months after discharge(5.0% vs 26.1% vs26.1%,P<0.001)and primary endpoint events were lower at 12 months after discharge(34.2% vs 54.9% vs 54.3%,P<0.001).LTA-ADP method(51.72 vs21.65 vs 26.17,P<0.001),PL-AA method(40.92 vs 37.68 vs 37.73,P=0.004),PL-ADP method(50.14 vs 44.56 vs 45.05,P<0.001),VASP phosphorylation method(65.28 vs 23.46 vs 23.50,P<0.001)and Verifynow method(147 vs 9vs 10,P<0.001)showed statistically significant differences among the three groups.(3)LTA-ADP method(AUC=0.609,P<0.001),VASP method(AUC=0.663,P=0.001)and Verifynow method(AUC=0.631,P=0.045)could predict all bleeding events within three months after discharge.LTA-ADP method(AUC=0.641,P<0.001),VASP method(AUC=0.591,P=0.022)and Verifynow method(AUC=0.627,P=0.015)was also able to predict all bleeding events within one year.In addition,LTA-ADP method(AUC=0.596,P=0.406)and VASP phosphorylation method(AUC=0.745,P=0.013)were also useful in predicting the occurrence of BARC2、3、5 bleeding within one year.To a certain extent,the combined prediction with multi-platelet testing methods can improve the prediction ability of all bleeding events occurring within three months,but has little effect on the improvement of the prediction ability of all bleeding events occurring within one year.ConclusionPlatelet reactivity tests in patients undergoing dual antiplatelet therapy after PCI has certain value in predicting bleeding events.Platelet reactivity tests value had a low to moderate correlation with out-of-hospital bleeding events in patients with ACS.The predictive value of platelet reactivity test results for bleeding within 3 months was higher than that for bleeding events within 12 months.The results of VASP phosphorylation showed that PRI had the highest predictive value for all bleeding events within 3 months and BARC2、3、5 bleeding events within 12 months after discharge.The combination of multiple platelet reactivity testing methods could not significantly improve the ability to predict medium-term or long-term bleeding events.Only VASP phosphorylation method combined with one or more other methods had a moderate ability to predict all bleeding events within 3 months.