The Efficacy And Safety Of Fondaparinux In Treatment Of Acute Coronary Syndrome

ObjectiveAcute coronary syndrome (ACS) is a common clinical cardiovascular event, which is acute and critically ill and prone to sudden death. The main pathogenesis is that thrombosis induced by rupture of unstable plaque causes complete or incomplete occlusion of coronary artery. Revascularization and the use of antiplatelet and anticoagulant drugs will improve the prognosis of ACS patients significantly.Thus, the antithrombotic treatment, including anticoagulation and anti-platelet is an important control method for ACS. But inappropriate medication may lead to increasing bleeding complications. Anticoagulant drugs including unfractionated heparin and low molecular weight heparin are commonly used in the treatment of acute coronary syndrome (ACS). Because of the instability of unfractionated heparin drug metabolism and pharmacokinetics, there are large individual differences in its anticoagulant effects.And the thrombocytopenia (HIT) incidence radio is high. Compared to unfractionated heparin, low-molecular-weight heparin have many advantages. But a thrombocytopenia (HIT) risk caused by low-molecular-weight heparin still exist.With the joint application of antiplatelet, anticoagulant drugs and coronary revascularization,the incidence of thrombotic events in ACS patients is becoming lower,while obvious rise of the incidence of bleeding complications appears.The bleeding events in patients with acute coronary syndrome (ACS) increase both the risk of death and the severe economic burden on patients.So, there is an urgent need to take the new anticoagulant drugs which are effective and safe into account.Fondaparinux is a synthetic with five sugar chain units, the structure of which is the structural basis of its anticoagulant effect. Fondaparinux is combined with the structure of antithrombin (AT) by the ratio of1:1to inhibit the activity of factor Xa and interrupt the coagulation cascade. PT and APTT, respectively, are the evaluation indicators of the extrinsic coagulation system and the intrinsic coagulation system. Several foreign large randomized controlled clinical trials had demonstrated the efficacy and safety of Fondaparinux which is applied in acute coronary syndrome (ACS), while domestic similar trials and reports are not much. In the clinical monitoring, some scholars hold the point that the application of fondaparinux in ACS patients does not affect the normal blood coagulation experiments such as plasma prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (APTT) or activated clotting time (ACT).While others argue that it can lead to plasma prothrombin time (PT) or activate activated partial thromboplastin time (APTT) mildly abnormal. So, is the PT (prothrombin time) or APTT (activated partial thromboplastin time) changed after ACS patients using fondaparinux? And does this answer have some clinical significance? This study is designed for the above problems, and to observe the efficacy and safety of fondaparinux in treatment of acute coronary syndrome.Method92patients with ACS were enrolled according to Guidelines for the diagnosis and treatment of of Patients with ACS made by ESC in2007.All the patients were randomly divided into experimental group (60cases)and control group(32cases). Besides the same basic treatment,such as aspirin, clopidogrel, nitroglycerin, cholesterol lowering medications,beta-blockers and Ⅱ b/Ⅲa receptors,except heparin or other low molecular weight heparin,the experimental group was given fondaparinux2.5mg per day subcutaneously for8days or until discharged and5000U low molecular weight heparin was administrated to the control group subcutaneously every12hours for8days or until discharged.Both the two groups were checked blood clotting before anticoagulation and re-checked after2days’ treatment. Patients of the two groups were treated with coronary angiography and PCI. Occurrences of cardiac disease and hemorrhage were observed in hospital and at30days. Statistical methods:(x±s) was adopted in measurement data.T test and Wilcoxon rank test were used for the significance test of count data.χ-test and Fisher exact probability test were adopted for efficacy and safety test,and α=0.05.Results1Comparison of Occurrence of cardiovascular events and hemorrhage in two groupsFollow-up in hospital:There were2cases (3.33%) of cardiovascular events and2cases (3.33%) of minor bleeding, including2cases of angina pectoris, no acute myocardial infarction or cardiovascular death in experimental group. There were2cases (6.25%) of cardiovascular events and4cases (12.50%) of minor bleeding, including2cases of angina pectoris, no acute myocardial infarction or cardiovascular death in control group. Occurrence of cardiovascular events had no difference between the experimental group and control group (3.33%vs6.25%, P=0.423). While occurrence of hemorrhage in the experimental group was obviously less than that of the control group (3.33%vs.12.50%, P=0.001).Follow-up at30days:There were5cases (8.33%) of cardiovascular events and2cases (3.33%) of minor bleeding, including5cases of angina pectoris, no acute myocardial infarction or cardiovascular death in experimental group.There are3cases (9.38%) of cardiovascular events and4cases (12.50%) of minor bleeding, including3cases of angina pectoris, no acute myocardial infarction or cardiovascular death in control group. No significant difference was observed in terms of cardiovascular events at30days for the experimental group vs. the control group (8.33%vs.9.38%, P=0.573).And occurrence of hemorrhage in the experimental group was still less than that of the control group (3.33%vs.12.50%, P=0.001).2PT and APTT in two groupsBefore anticoagulant treatment, PT value between the experimental group and control group had no significant difference (P=0.063), and APTT value between the experimental group and control group had no significant difference (P=0.225). In the experimental group, PT value on3rd day of anticoagulant treatment, compared with it on admission, was statistically significant (P=0.000), and so was APTT value (P=0.000). In the control group, PT value on3rd day of anticoagulant treatment, compared with it on admission, had no significant difference (P=0.845), and so did APTT value (P=0.184). Occurrence of cardiovascular events had no difference between the experimental group and control group (3.33%vs6.25%, P=0.423). Occurrence of hemorrhage in the experimental group was obviously less than that of the control group(3.33%vs.12.50%, P=0.001). On3rd day of anticoagulant treatment, PT value between the experimental group and control group was statistically significant (P=0.008), and APTT value between the experimental group and control group was statistically significant (P=0.039).Conclusion1. Fondaparinux was shown to have comparable efficacy to LMWH.2. Fondaparinux was shown to have be safer than LMWH.3. Fondaparinux have some influence on PT and APTT.4.The monitoring of PT and APTT value is not needed when fondaparinux is applicated in acute coronary syndrome (ACS) patients.