Effect Of Dual Pathway Inhibition Therapy On Platelet Function In Patients With Acute Anterior Myocardial Infarction

BackgroundAcute ST-segment elevation myocardial infarction is a serious coronary atherosclerotic disease,which is one of the main causes of death and disability,and seriously threatens people’s health.STEMI is an acute vascular obstruction caused by the rupture or erosion of atherosclerotic plaque,which induces thrombosis.Platelets plays a very important role in the formation of thrombus in acute myocardial infarction.Dual antiplatelet therapy,including aspirin and a P2Y₁₂ receptor inhibitor,improved overall outcomes and became a routine medication recommended by guidelines after percutaneous coronary intervention.However,individual differences in platelet reactivity put patients at increased risk of adverse events,especially stent thrombosis.Both high and low platelet reactivity are risk factors for adverse events after PCI in STEMI patients.Anticoagulants are also widely used before and after PCI to prevent coronary thrombosis.Several clinical trials have included Dual pathway inhibition therapy in the treatment of coronary heart disease in addition to antiplatelet therapy with long-term oral anticoagulants.Low-dose rivaroxaban（2.5mg twice daily）combined with DAPT in patients with recent acute coronary syndrome reduced the risk of composite endpoint death and increased bleeding events without increasing the risk of fatal bleeding.Low-dose rivaroxaban combined with aspirin in the treatment of chronic cardiovascular disease can significantly reduce major cardiovascular adverse events,but does not increase fatal bleeding,vital organ bleeding and intracranial bleeding.The GEMINI-ACS-1 trial suggested that rivaroxaban combined with P2Y₁₂ receptor inhibitors had similar efficacy as DAPT in the treatment of ACS,with similar clinical bleeding risk.However,the mechanism behind this effect is still unknown.Tobias Petzold’s study suggested that rivaroxaban had certain antiplatelet effect,which was independent of the anticoagulant ability of thrombin and Rivaroxaban.However,the effect of Dual pathway inhibition therapy on platelet function in STEMI patients remains to be explored.PurposesIn this prospective clinical study,aspirin combined with ticagrelor was applied after acute anterior myocardial infarction,and aspirin was replaced with low-dose rivaroxaban 3 days later.The effect of dual pathway therapy with rivaroxaban combined with ticagrelor on platelet function compared with dual antiplatelet therapy was investigated by thrombologram.MethodsPatients with acute anterior myocardial infarction eligible for inclusion were screened.Random number table method was used to divide patients with acute anterior myocardial infarction eligible for inclusion into DPI group and DAPT group in a ratio of 2:1.All patients with acute anterior myocardial infarction received oral aspirin（300 mg）and ticagrelor（180mg）before coronary angiography,and aspirin（100 mg 1/day）plus ticagrelor（90 mg 2/day）combined with low molecular weight heparin anticoagulant therapy after PCI.After 3 days of treatment,low molecular weight heparin was stopped in the DPI group,and the DAPT regimen was changed to rivaroxaban（2.5 mg 2/day）ticagrelor（90 mg 2/day）.After 3days of treatment,low molecular weight heparin therapy was discontinued in the DAPT group,and the regimen of aspirin（100 mg 1/day）plus ticagrelor（90 mg 2/day）was continued.During hospitalization,the thrombogram on the 3rd day and the 6th day after PCI were performed,and the ultrasonic cardiogram within the 7th day after PCI was performed,and the patient’s age,gender,smoking history,drinking history,blood lipid and other data were collected.ResultsThere were no statistically significant differences between the two groups in gender,age,body mass index,smoking and drinking history,complicated diseases（such as cerebral infarction,hypertension,diabetes,and hyperlipidemia）,previous PCI surgery,Killip grade≥2,laboratory related indicators,clotting related indicators,cardiac ultrasound,and PCI treatment criteria.There were no significant differences in baseline thromboelastogram response time（R）,clot formation kinetics（K）,hemagglutination rate（αAngle）,MA,and coagulation index（CI）between the two groups.There was no significant difference between the two groups in baseline platelet inhibition rate,AA or ADP-induced platelet fibrin clot intensity（MAAA or MAADP）,or AA or ADP pathway platelet inhibition rate.On the third day after DPI replacement,the response time in DPI group（6.61±1.19min）was longer than that in DAPT group（6.03±0.59min）,and the difference was statistically significant（P=0.014）.There was no significant difference in K value,αAngle,MA value and CI value between the two groupsOn the third day after DPI replacement,MAAA in DPI group（35.80±13.14 mm）was significantly higher than that in DAPT group（27.04±11.72 mm）（P=0.014）.The relative platelet inhibition rate of AA pathway in DPI group（59.58±25.15%）was significantly lower than that in DAPT group（76.19±18.57%）（P=0.005）.There was no significant difference in platelet fibrin clot strength induced by ADP or relative platelet inhibition rate of MAADP and ADP pathways.Conclusions1.Dual pathway treatment with low-dose rivaroxaban combined with ticagrelor did not directly affect ADP-induced platelet fibrin clot strength and platelet inhibition rate in patients with acute anterior myocardial infarction.2.There was no significant difference in the rate of fibrin and platelet at the onset of clot formation or in the maximum strength and stability of fibrin and platelet clot formation between aspirin combined with ticagrelor and low-dose rivaroxaban combined with ticagrelor.3.Compared with aspirin combined with ticagrelor,Low dose rivaroxaban combined with ticagrelor prolonged coagulation initiation...