A Clinical Study In The Very Old Patients With Coronary Heart Disease Treated With Different Anti-platelet Agents

Anti-platelet therapy is a cornerstone of cardiovascular medicine. Aspirin has been used widely in primary and secondary prevention and treatment in cardial-vascular diseases. It exerts its anti-platelet effect by acetylation of the platelet cyclo-oxygenase, resulting in an irreversible inhibition of platelet-dependent thromboxane formation . Aspirin every another day has significantly effect in the primary prevention of cardiovascular diseases by WHS and PHS study. but lack of evidence in secondary prevention of cardiovascular diseases.Clopidogrel is a new anti-platelet drug, which has been used in clinical. But its effect in prevention of cardiovascular diseases in very old patients is still uncertain. In recent years people find that aspirin antiplatelet effect is not uniform in all patients and its inhibition of platelet aggregation is subject inter-individual and intra-individual variability. Aspirin resistance has been defined both as a clinical entity (thrombotic event while taking aspirin) and by a myriad of altered biomarkers and enhanced platelet function testing. But the Clinical characteristic of aspirin resistance in the older patients with coronary heart diseases is still uncertain.Objective: 1,To study the Anti-platelet effects and safety of different doses of aspirin at different times intervals in elderly patients with coronary heart disease.2,To detect the anti-platelet effect, the risk of bleeding, the side effects on neutrophils and platelets in using different doses and different forms of antiplatelets agents in elderly patients with coronary heart disease. And to find both an optimal dose for the very old cardiovascular patients.3,To study the clinical characteristics and incidence of Aspirin resistance or aspirin semi-responders in very old patients with coronary heart disease.Method:349 old patients aged more than 60 with coronary heart disease were enrolled in the study. Those with blood diseases, hepatic disfunction, active gastrointestinal ulcer, a history of recent surgery allergy to aspirin, and a history of injury or bleeding in recent two weeks were excluded. The patients were randomized to 3 studies:study1: group with aspirin 75 mg daily, group with aspirin 100 mg every another day , group with aspirin 100 mg daily, group with aspirin 150 mg every another day, group with aspirin 150 mg daily and placebo group .study2: group with aspirin 75mg daily, group aspirin 100mg daily ,group 3 clopidogrel 25mg daily, group clopidogrel 50mg daily and placebo group.study3: other patients with coronary heart disease received aspirin (100 mg/d for 7 days) were enrolled in the study.The treatment was continued for seven days .Before and after the study, blood specimens were collected from all eligible patients to test platelet aggregation rate,the blood routine values,coagulation system.Results: 1,Each aspirin treatment group in this study could inhibit platelet aggregation significantly compared with placebo (p<0.05),Aspirin 75 mg daily and aspirin 100 mg every another day; aspirin 100 mg daily and aspirin150 mg every another day have no significantly differences in platelet aggregation (p>0.05) . The decrease in neutrophil or platelet did not occur in all eligible patients.2,Aspirin and clopidogrel in this study could inhibit platelet aggregation significantly compared with placebo (p<0.05) ,clopidogrel was more effective than aspirin , aspirin 75 mg daily and aspirin 100 mg daily have no significant differences in platelet aggregation by AA,ADP (p>0.05) aspirin 100 mg daily and clopidogrel 50 mg daily were significantly difference in platelet aggregation by ADP (p<0.05) , aspirin 100 mg daily and clopidogrel 50 mg daily have no significantly difference in platelet aggregation by AA (p>0.05). aspirin and clopidogrel had no effect on coagulation system.The decrease in neutrophil or platelet did not occur in all eligible patients .3,There were the 10(7.7%) of the patients being Aspirin resistance and 22(17.2%) of being Aspirin semi-responders. Aspirin resistance or aspirin semi-responders were significantly correlated with 2-diabetes mellituhis,female,smoking and CD62p. Conclusions:1,Both aspirin 75 mg daily and aspirin 100 mg every another day could inhibit platelet aggregation definitely and safety in elderly patients with cardiovascular diseases. So do the aspirin 100 mg daily and aspirin 150 mg every another day.2,Aspirin 75 mg daily and aspirin 100 mg daily have the same effects in anti-platelet aggregation .The most effective anti-platelet agent was Clopidogrel 50 mg daily, then aspirin 100 mg daily, aspirin 75 mg daily in turn, there was a tendency that Clopidogrel 50 mg daily causes less side-effect than aspirin 100 mg daily.3,Aspirin resistance or aspirin semi-responders is likely correlated with 2-diabetes mellituhis,female,and smoking (p<0.05). CD62p is the way of detecting Aspirin resistance or aspirin semi-responders. The detection of aspirin resistance is particularly important for the large number of patients relying on this medication for anti-therapy and prevention of cardiovascular events. The safe alternative anti-platelet agent for long administration should be used if aspirin resistance appears to be an emerging direction of anti-platelet therapy.