| Background and Objective In recent years, antiplatelet therapy in patients with acute coronary syndromes(ACS) becomes more and more important. Clopidogrel is a new thienopyridine derivative which has been shown to reduce morbidity and mortality in ACS, especially after percutaneous coronary interventions(PCI). It has been demonstrated that the prognosis in patients who accepted aspirin and clopidogrel is better. At present, the treatment course of clopidogrel is about 1 year. However, some trials suggest long-term (> 1 year)clopidogrel therapy may achieve extra better prognosis for ACS. To investigate whether long-term dual antiplatelet (aspirin and clopidogrel) treatment is associated with better prognosis for ACS, we attempted to retrospectively evaluate the efficacy and safety of the long-term dual antiplatelet regimen. Moreover, in order to provide experimental evidence for clinical application of dual antiplatelet regimen, we analyzed the effects of clopidogrel on platelet function in elderly patients with coronary heart disease (CHD).Methods From June 2005 to June 2006, a total of 338 hospitalized patients with ACS were enrolled in our hospital. They were assigned to aspirin group(groupl, administerd asprin as a single antiplatelet therapy regimen after discharge, n=93 ), dual antiplatelet treatment 1 year group(group2, administerd asprin and clopidogrel as a dual antiplatelet therapy regimen after discharge for 6 to 12 months, then keep on administering asprin, n=127) and dual antiplatelet treatment 2 year group(group3, administerd asprin and clopidogrel as a dual antiplatelet therapy regimen after discharge for 2 years, n=118). The follow-up period for all the patients was 2 years. It was retrospectively analyzed and compared between them in clinical data (basic clinical data, drug treatment data, platelet count, coagulation indexes and serum lipids indexes), primary end point (cardiovascular death, nonfatal myocardial infarction and stroke) and hemorrhagic events (major hemorrhage, moderate hemorrhage and minor hemorrhage) within 1 and 2 years.From January of 2007 to June of 2007, 32 hospitalized patients of CHD were enrolled in our hospital. ADP-induced platelet aggregation ratio, the maximum amplitude (MAThrombin,MAadp) and ADP-induced platelet inhibition ratio were measured before and after taking clopidogrel for 7 days by two detective methods (thrombelastograph and optical aggregometry) and evaluated the clinical significance of two different detective methods.Results (一) Retrospective clinical study: The baseline clinical characteristics were compared for the three groups, there are no difference significantly among them (p>0.05) .At 1 year, platelet count, coagulation indexes and serum lipids indexes did not differ significantly among the three groups. The difference was not statistically significant in the platelet count, coagulation indexes(TT,APTT,PT,PTA) between 1 year and the before therapy. FIB was significantly decreased (p < 0.05). Lipids indexes (TC,TG,LDL) were significantly decreased (p < 0.01) ,and HDL was significantly increased (p < 0.01). At 1 year, compared with groupl, the cardiovascular death rate and combined end point of group2 and group3 were significantly decreased[ (9.68% vs 2.36%, p<0.05),(13.98% vs 4.72%, p< 0.05) ] [ (9.68% vs 2.54%, p<0.05),(13.98% vs 5.08%,p<0.05) ]; nonfatal myocardial infarction and stroke of group2 and group3 had no statistical significance [ (2.15% vs 1.57%,p>0.05),(2.15% vs 0.79%,p>0.05)] [ (2.15% vs 1.69%,p>0.05),(2.15% vs 0.85%,p>0.05) ]. The difference was not statistically significant between group2 and group3. The difference of hemorrhagic events (major hemorrhage, moderate hemorrhage and minor hemorrhage) were not statistically significant among the three groups at 1 year.At 2 years, platelet count, coagulation indexes and serum lipids indexes had no difference significantly among the three groups. The difference was not statistically significant in the platelet count, coagulation indexes(TT,APTT,PT,PTA) between 2 year and the before therapy. FIB was significantly decreased (p < 0.05). Lipids indexes (TC,TG,LDL) were significantly decreased (p < 0.01) ,and HDL was significantly increased (p < 0.01). All of them at 1 year and 2 years had no statistical significance (P>0.05). At 2 years, compared with group1, the cardiovascular death rate and combined end point of group2 and group3 were significantly decreased[ (15.10% vs 6.30%, p<0.05),(26.88% vs 13.39%, p <0.05)] [(15.10% vs 5.93%, p<0.05),(26.88% vs 11.86%, p<0.05)];nonfatal myocardial infarction and stroke of group2 and group3 had no statistical significance [(6.45% vs 3.94%, p>0.05),(5.38% vs 3.15%, p>0.05)] [(6.45% vs 3.39%, p>0.05),(5.38% vs 2.54%, p>0.05) ]. The difference was not statistically significant between group2 and group3. The difference of hemorrhagic events (major hemorrhage, moderate hemorrhage and minor hemorrhage) were not statistically significant among the three groups at 2 years (p >0.05) .(二) Prospective platelet function trial: The aim of the investigation was to compare the effects of clopidogrel on platelet function in 32 elderly patients with CHD by thrombelastograph and optical aggregometry. We found clopidogrel could significantly increase platelet inhibition ratio (50.06±16.98% vs 18.28±7.94%,p < 0.01) and decrease MAADP (38.10±11.87mm vs 57.84±8.26mm, p < 0.01) and the platelet aggregation ratio (52.73±10.72% vs 74.06±6.60%, p< 0.01).Conclusion Long-term dual antiplatelet treatment for patients with ACS has been shown to significantly decrease the incidence of cardiovascular death. Especially, There was a downtrend in the patients who continuously administrated dual antiplatelet treatment for 2 years in comparison to the patients who only administrated clopidogrel for 1 year at 2 years, but there was no significant difference ( P>0. 05). The risk of severe hemorrhage did not increase. Experimental evidence has shown a significant platelet inhibition by clopidogrel could be demonstrated in elderly patients with CHD.
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