| Harken and his colleagues successfully performed aortic valve replacement with cage ball mechanical valve in 1960, which marks the start of clinical application of first generation mechanical heart valves. After the development from the second generation single-leaf tilting disc valve to the third generation of double-leaf mechanical valve, mechanical valve has got a long-term development in the treatment of heart valve disease. According to the history of mechanical heart valve, good hemodynamic performance, stability, durability, and less postoperative complications is the direction of its development. The implantation of mechanical valve in the human body can cause thrombosis and embolism, which are the major causes of patients'disability and death. Combined the cardiovascular risk factors including advanced age, smoking, diabetes, hypertension, hyperlipidemia, atrial fibrillation, stroke and transient cerebral ischemia (TIA), mechanical heart valve replacement surgery cause high risk of cardiovascular events. Studies have shown that thromboembolic complications occurs most frequently in the 3 to 6 months after mechanical heart valve replacement, and incidence rate of postoperative thromboembolic in early stage is seven times higher than the next several years. Therefore, it is necessary to carry on anticoagulation therapy in the early stage after mechanical heart valve replacement, in order to prevent the occurrence of thromboembolism.Warfarin is a vitamin K antagonist. At present, it is the only oral anticoagulation drug that can be used for the prevention of thromboembolism complications after mechanical heart valve replacement. But there are individual differences in the efficacy of warfarin. Its disadvantage is slow onset, narrow therapeutic window, need 2-7 days to achieve the therapeutic effect of anticoagulant treatment, prone to thrombosis or bleeding complications, accounted for 75% of all postoperative complications. Therefore, it is necessary to frequently monitor the coagulation function and timely adjust the drug dosage, which caused great inconvenience to the patient's treatment and affected the patient's long-term anticoagulant therapy compliance. Although there are many deficiencies, but so far, it has an irreplaceable position in the anticoagulation therapy after mechanical heart valve replacement.At present, aspirin is the most basic antiplatelet drugs, the role of cyclooxygenase-1 directly inhibits thromboxane A2 synthesis, inhibition of platelet adhesion, aggregation and release, prevent thrombus formation and development. The guideling of the European and the United States recommended aspirin as the only drug for the first prevention of cardiovascular disease, and the domestic scholars have been widely recognized as the anti-thrombotic drugs for the second prevention of cardiovascular disease. Aspirin can also be used to prevent the formation of artificial heart valve, long-term bed patients or postoperative. But no studies have shown that the use of antiplatelet drugs alone can safely prevent the occurrence of thrombosis in patients with mechanical heart valve replacement and long-term use of antiplatelet drugs can cause peptic ulcer and gastrointestinal bleeding.The new oral anticoagulants, such as dabigatran, seems to make up for deficiencies of warfarin, but there was higher thromboembolism and bleeding complications compared with warfarin, so it is currently banned for anticoagulation therapy in patients with mechanical heart valve replacement.Combined warfarin and aspirin seems to have potential and attractive anti-thrombosis complementary, especially suitable for the patients with cardiovascular risk associated with atrial fibrillation, hypertension, diabetes, coronary heart disease and other factors of the disease. After oral administration of aspirin by gastrointestinal absorption,1 hour to reach the peak plasma concentration, and can also compensate the deficency of warfarin. Warfarin and aspirin combined with anticoagulation than warfarin alone can reduce thromboembolic events, but significantly increased the risk of bleeding. The increased risk of bleeding appears to be related to the dose of aspirin, which may reduce the risk of bleeding complications as lower dose aspirin. Based on the above research, we oberve the the incidence rate of hemorrhage and thromboembolism and to evaluate safety and efficacy of combined low dose aspirin and warfarin in patients after mechanical heart valve replacement. This study is divided into two sections to elaborate.Part 1 The study of early anticoagulation therapy with associated low doseaspirin and warfarin after mechanical heart valve replacementObjectives:The early postoperative of mechanical heart valve replacement is the high incidence of thrombosis and embolism. The aim of this study was designed to evaluate the safety and efficacy of associated low dose aspirin and warfarin therapy after mechanical heart valve replacement.Methods:A total of 1146 patients were randomly divided into study (warfarin plus 75-100 mg aspirin) group and control (warfarin plus placebo) group after mechanical heart valve replacement. International normalized ratio (INR) was maintained at 1.8-2.2 for mitral mechanical valve or double valve and 1.5-2.0 for aortic mechanical valve, respectively. Platelet count, platelet aggregation and heart function tests, carotid ultrasonography were performed, and cerebral CT examination was performed in patients with symptoms and signs of cerebral vascular disease before and after surgery. Record the occurrence of major hemorrhage and thromboembolic events.Results:All patients were followed up for 6 months. The average dose of warfarin in the study group was (2.84+1.02) mg/day, the control group was (2.87+1.11) mg/day, there were no significant statistically difference between the two groups (P> 0.05). Platelet counts were significantly increased compared with preoperative in both groups in 7 days,1 month and 6 months after surgery. The difference was statistically significant (all P<0.01). However, there was no significant difference in platelet count between the two groups at the same time points (P>0.05). The platelet aggregation in the study group was significantly lower than that of in the control group at 7 days,1 month and 6 months after surgery, and there was significantly higher than that of preoperative in the control group. The difference was statistically significant (all P<0.05). The incidence of thromboembolism in the study group was lower than in the control group(1.75% vs.3.66%, P=0.045). There was no significant statistically difference in incidence of bleeding (3.49% vs.3.84%, P=0.753) or mortality (0.35% vs.0.52%, P=0.654) between the two groups.Conclusions:Aspirin can make up for the lack of warfarin in the early postoperative after mechanical heart valve replacement. Combined low-dose aspirin and warfarin anticoagulant therapy can further reduce the incidence of thrombosis and thromboembolism than warfarin alone. Combined anticoagulant therapy did not increase the risk of bleeding and mortality.Part 2 The study on the benefit and risk of associated anticoagulation in patients with mechanical heart valve replacement combined with cardiovascular risk factorsObjectives:With cardiovascular risk factors in patients with mechanical heart valve replacement are at high risk of cardiovascular events and anticoagulation-related complications. This study was to further discuss the benefits and risks of associated postoperative anticoagulant therapy.Methods:A total of 925 patients with cardiovascular risk factors (age?50 years old, smoking, hyperlipidemia, hypertension, diabetes mellitus, atrial fibrillation, stroke/TIA) were randomly divided into study (warfarin plus 75-100 mg aspirin) group and control (warfarin plus placebo) group following mechanical heart valve replacement. All of them were detected in INR, blood biochemistry (myocardial enzymes, lipids, blood glucose), and electrocardiogram, cardiac and carotid ultrasound, cranial CT or MRI during the postoperative follow-up, to record the occurrence of cardiovascular endpoint events and anticoagulation related complications.Results:All patients were followed up for 0.5 to 3.5 years, with a total of 1907.3 patient-years (Pty). The mean dosage of warfarin in study group was (2.85 ± 1.09) mg/day and (2.88 ± 1.20) mg/day in the control group, there was no statistically significant difference between the two groups (P>0.05). In the follow-up period, there were 83 cases of cardiovascular endpoint events (4.35% Pty), including 33 cases in the study group (3.46% Pty),50 cases in the control group (5.25% Pty), there was statistically significant difference between the two groups (P=0.049). There were 17 cases of thrombosis (1.78% Pty) in the study group and 31 cases (3.25% Pty) in the control group, the difference was statistically significant (P= 0.037). Total of bleeding occurred in 73 cases (3.83% Pty), of which 35 cases of study group (3.67% Pty), the control group of 38 cases (3.99% Pty), there was no significant statistically difference between the two groups (P>0.05).Conclusions:With cardiovascular risk factors of patients with mechanical heart valve replacement, low-dose aspirin and warfarin therapy decreased the incidence of cardiovascular endpoint events and thromboembolism compared with warfarin alone. There were no significant increase in the incidence of bleeding and death. Combined low-dose aspirin and warfarin anticoagulant therapy made significant benefit in patients with cardiovascular risk factors. |
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