Optimal Dual Antiplatelet Therapy In Medically Managed Patients With Acute Coronary Syndrome

Objectives1.Optimal dual antiplatelet therapy(DAPT)duration for medically managed acute coronary syndrome(MMACS)patients remains unknown.We explored the efficacy and safety of≥12-month DAPT among MMACS patients.2.Although current guidelines recommend ticagrelor in addition to aspirin as the antiplatelet strategy for MMACS patients,clinical evidence specific to this special population is lacking.Whether potent oral P2Y12 inhibitors should be used in MMACS patients is still under debate.Methods1.In this sub-analysis of the Optimal Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease study,clinical outcomes among MMACS patients were compared between the<12-month and≥12-month DAPT groups.The primary efficacy endpoint was a composite of cardiac death,myocardial infarction,and stroke.Safety endpoints included the Bleeding Academic Research Consortium(BARC)type 2,3 and5 bleeding,BARC type 3 and 5 bleeding,and all bleeding events.Propensity score matching(PSM)was used to compare baseline characteristics between the<12-month and≥12-month DAPT groups.2.We conducted a comprehensive search in Pub Med,Embase,Web of Science,and Cochrane Library to identify studies exploring the efficacy or safety of ticagrelor and prasugrel versus clopidogrel or placebo in MMACS patients.The primary efficacy endpoint was major adverse cardiovascular events(MACE)defined by each study,and the safety endpoint was TIMI non-CABG major bleeding.A total of 6102 records were screened,and 4 studies including 46,346 patients were finally included.Results1.In this cohort of acute coronary syndrome(ACS)patients(n=10016),MMACS patients(n=2967)were less likely to use DAPT at 12(31.64%vs 67.47%,P<0.0001)and 24(13.82%vs 18.71%,P<0.0001)months and experienced more ischemic events at 12(4.55%vs 3.40%,P=0.006)and 24(6.88%vs 5.08%,P=0.0004)months than those treated with percutaneous coronary intervention(n=7049).Among MMACS patients,the rate of primary efficacy endpoint occurring within the second year was significantly higher in the<12-month DAPT group than in the≥12-month group both before(2.88%vs 1.60%,P=0.040)and after(3.19%vs 1.71%,P=0.045)PSM.After PSM,no significant differences in all bleeding,BACR type 2,3 and 5 bleeding,BARC type 3 and 5 bleeding were found between the groups.2.The use of potent oral P2Y12 inhibitors significantly lowers the risk of MACE compared with clopidogrel(HR:0.90;95%CI:0.82-0.98;P=0.018;I~2=0%).A significant reduction in risks of all-cause death and myocardial infarction was also observed with the use of potent oral P2Y12 inhibitors compared with clopidogrel.No significant difference in risks of stroke or TIMI non-CABG major bleeding(HR:1.24;95%CI:0.90–1.73;P=0.191;I~2=0%)was observed between potent oral P2Y12inhibitors and clopidogrel.Conclusions1.MMACS patients with insufficient DAPT management experienced relatively more ischemic events.DAPT for at least 1 year may be beneficial to this special population without significantly increasing the bleeding risks.2.Potent oral P2Y12 inhibitors,especially ticagrelor,decrease the risk of ischemic events in MMACS patients as compared with clopidogrel,without significantly increasing major bleeding.