human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Either dipyridamole , a vasodilator known to reduce platelate adhesiveness and aggregation , or a placebo was given in a daily dose of 400 mg as a r and om , blind trial to 70 patients who had undergone prosthetic cardiac-valve replacement . Patients in both groups were given anticoagulation with warfarin sodium . Of 36 patients in the placebo group followed for 557 months systemic arterial embolism occurred in 17 per cent . Twenty-seven patients in the dipyridamole group followed for 393 months gave no clinical evidence of arterial embolism .  Dipyridamole was discontinued shortly after surgery in seven patients , and these were followed for 110 months . In two of them cerebral emboli developed six months after treatment was discontinued . It is tentatively concluded that the addition of dipyridamole to a program of anticoagulation reduces the frequency of postoperative arterial emboli originating on prosthetic cardiac valves in patients who can tolerate the drug Authors studied the effect of coumarin , and its combination with low-dose ( 125 mg/day ) acetylsalicylic acid in the prevention of thromboembolic complication during a 10-year period ( average 4.7 years ) in a r and omized trial of 296 patients aged 18 - 60 year with tilting disc type prosthetic heart valve ( 159 mitral and 137 aortic ) in sinus rhythm . In the group treated with coumarin ( 152 patients , 743.4 patient-years ) 4 cases ( 2 of them fatal ) of valve thrombosis , 12 cases of peripheral embolism and 9 cases ( 3 intracranial , 3 among them fatal ) of major bleeding were observed ; in the group treated with coumarin plus acetylsalicylic acid ( 144 patients , 638.7 patient-years ) 2 cases ( 1 of them fatal ) of valve thrombosis , 4 cases of peripheral embolism and 14 cases ( 3 of them fatal ) of major bleeding were observed . In the case of valve thromboses the difference between the two groups was non-significant but still clinical ly remarkable ; peripheral embolism occurred in significantly higher number ( p < 0.05 ) . There was no statistically significant difference of bleeding complications between the two groups . The results suggest that the combination of coumarin plus low-dose acetylsalicylic acid is more effective in the prevention of thromboembolic complications in patients with mitral and aortic prosthetic heart valve than coumarin alone ; the danger of bleeding complications seems to be acceptable with adequate control Despite the use of oral anticoagulation in patients with prosthetic heart valves , persistent thromboembolism over time warrants a search for improved methods of prevention . Thus , patients receiving 1 or more mechanical prosthetic heart valves were r and omized to therapy with warfarin plus dipyridamole ( 400 mg/day ) or warfarin plus aspirin ( 500 mg/day ) on the basis of location and type of valve and surgeon , and followed up with a concurrent , nonr and omized control group taking warfarin alone . In 534 patients followed up 1,319 patient-years ,  excessive bleeding ( necessitating blood transfusion or hospitalization ) was noted in the warfarin plus aspirin group ( 23 of 170 [ 14 % ] , or 6.0/100 patient-years ) compared with warfarin plus dipyridamole ( 7 of 181 [ 4 % ] , or 1.6/100 patient-years , p less than 0.001 ) , or warfarin alone ( 9 of 183 [ 5 % ] , or 1.8/100 patient-years , p less than 0.001 ) . A trend was evident toward a reduction in thromboembolism in the warfarin plus dipyridamole group ( 2 of 181 [ 1 % ] , or 0.5/100 patient-years ) as compared with warfarin plus aspirin ( 7 of 170 [ 4 % ] , or 1.8/100 patient-years ) , or warfarin alone ( 6 of 183 [ 4 % ] , or 1.2/100 patient-years ) . Adequacy of anticoagulation ( based on 12,720 prothrombin time determinations ) was similar in all 3 groups with 65 % of prothrombin times in the therapeutic range ( 1.5 less than or equal to prothrombin time/control less than or equal to 2.5 ) , 30 % too low , and 5 % too high . Warfarin plus aspirin therapy result ed in excessive bleeding and is contraindicated . Longer follow-up study is needed to determine whether further separation of the incidence of thromboembolism can be detected BACKGROUND Mechanical heart valve replacement requires lifelong anticoagulant treatment . Aspirin has proved useful in further reducing thromboembolic events when added to oral anticoagulants . However , increased ( gastrointestinal ) bleeding was observed at the doses previously tested for this combination in heart valve prostheses . METHODS We performed a prospect i ve r and omized trial to compare the combination of low-intensity oral anticoagulants ( international normalized ratio 2.5 to 3.5 ) plus aspirin ( 100 mg/day ) ( arm A ) versus high-intensity oral anticoagulants alone ( arm B ) ( international normalized ratio 3.5 to 4.5 ) . Arm A included 258 patients and arm B 245 patients . The two groups were comparable for all baseline characteristics . RESULTS The outcomes of the study were embolism , valve thrombosis , and major hemorrhage . The median follow-up was 23 months . The two treatments offered similar antithrombotic protection . The incidence of embolic episodes was 1.32 per 100 patient-years ( 95 % confidence interval 0.53 to 2.7 ) for arm A and 1.48 per 100 patient-years ( 95 % confidence interval 0.59 to 3.03 ) for arm B. Major hemorrhage occurred in 1.13 per 100 patient-years ( 95 % confidence interval 0.41 to 2.45 ) for arm A and 2.33 per 100 patient-years ( 95 % confidence interval 1.17 to 4.14 ) for arm B. Gastrointestinal bleeding was not increased by this combined reduced dose of aspirin and coumarin OBJECTIVE Antiplatelet agents are used for prevention of thromboembolism in surgical patients and in patients with chronic atrial fibrillation . Up to date , however , results of r and omized studies comparing antiplatelet agents and oral anticoagulation have not been reported . The aim of this study was to compare the efficacy and safety of triflusal ( an antiplatelet agent ) versus acenocoumarol for primary prevention of thromboembolism in the early postoperative period after implantation of a bioprosthesis . METHODS In this prospect i ve , multicentric , r and omized , open pilot trial , patients were assigned to treatment with triflusal ( 600mg/d ) or acenocoumarol ( target INR 2.0 - 3.0 ) . Study medication was started 24 - 48h after valve replacement with a bioprosthesis , and continued for 3 months . Four follow-up visits were scheduled : baseline , and at 1 , 3 and 6 months thereafter . The primary end-point was a composite of the rate of thromboembolism , severe hemorrhage and valve-related mortality . RESULTS A total of 193 patients were included ( 97 received triflusal and 96 acenocoumarol ) , with a mean age of 72.5 years . Half were men . Aortic valve replacement was performed in 181 patients ( 93.8 % ) , mitral valve replacement in 10 patients ( 5.2 % ) and double valve replacement in 2 ( 1.0 % ) . Hospital mortality was 11 ( 5.7 % ) . Primary outcome was recorded in 9 patients with triflusal ( 9.4 % ) and in 10 patients with acenocoumarol ( 11 % ) . There were nine episodes ( 4.7 % ) of thromboembolism , six in the triflusal group and three in the acenocoumarol group , and three episodes of permanent neurological deficits , one in the triflusal group and two in the acenocoumarol group . Severe hemorrhage : nine episodes , six in the acenocoumarol group and three in the triflusal group . None of the observed differences in efficacy were statistically significant . Regarding safety , three patients in triflusal group reported at least one hemorrhage , compared to 10 in acenocoumarol group ( P=0.048 ) . CONCLUSIONS There were no significant differences in efficacy between both groups , however , triflusal showed a significantly lower incidence of bleeding episodes BACKGROUND Despite the use of warfarin , major systemic embolism remains an important complication in patients with heart-valve replacement . Although the addition of antiplatelet agents has the potential to reduce this complication , their efficacy and safety when given in combination with warfarin are uncertain . METHODS In a r and omized , double-blind , placebo-controlled trial , we assessed the efficacy and safety of adding aspirin ( 100 mg per day ) to warfarin treatment ( target international normalized ratio , 3.0 to 4.5 ) in 370 patients with mechanical heart valves or with tissue valves plus atrial fibrillation or a history of thromboembolism . RESULTS A total of 186 patients were r and omly assigned to aspirin  and 184 to placebo  , and they were followed for up to 4 years ( average , 2.5 ) . Major systemic embolism or death from vascular causes occurred in 6 aspirin-treated patients ( 1.9 percent per year ) and 24 placebo-treated patients ( 8.5 percent per year ) ( risk reduction with aspirin , 77 percent ; 95 percent confidence interval , 44 to 91 percent ; P < 0.001 ) . Major systemic embolism , nonfatal intracranial hemorrhage , or death from hemorrhage or vascular causes occurred in 12 patients assigned to aspirin ( 3.9 percent per year ) and 28 patients assigned to placebo ( 9.9 percent per year ) ( risk reduction , 61 per cent ; 95 percent confidence interval , 24 to 80 percent ; P = 0.005 ) ; major systemic embolism or death from any cause occurred in 13 patients ( 4.2 percent ) and 33 patients ( 11.7 percent ) , respectively ( risk reduction , 65 percent ; 95 percent confidence interval , 33 to 82 percent ; P < 0.001 ) ; and death from all causes occurred in 9 patients ( 2.8 percent ) and 22 patients ( 7.4 percent ) , respectively ( risk reduction , 63 percent ; 95 percent confidence interval , 19 to 83 percent ; P = 0.01 ) . Bleeding occurred in 71 patients in the aspirin group ( 35.0 percent ) , as compared with 49 patients in the placebo group ( 22.0 percent ) ( increase in risk , 55 percent ; 95 percent confidence interval , 8 to 124 percent ; P = 0.02 ) ; major bleeding occurred in 24 and 19 patients , respectively ( increase in risk , 27 percent ; 95 percent confidence interval , -30 to 132 percent ; P = 0.43 ) . CONCLUSIONS In patients with mechanical heart valves and high-risk patients with prosthetic tissue valves , the addition of aspirin to warfarin therapy reduced mortality , particularly mortality from vascular causes , together with major systemic embolism . Although there was some increase in bleeding , the risk of the combined treatment was more than offset by the considerable benefit Patients who had undergone prosthetic valve replacement were treated with warfarin ( anticoagulant ) alone or in combination of ticlopidine ( 200 mg/day ) or aspirin ( 81 mg/day ) ( anti-platelet agents ) . The study of blood coagulation factors and platelet aggregation were carried out with these cases . 1 ) The patients ( n = 24 ) receiving  warfarin for 21 days after prosthetic valve replacement revealed marked increases in PIVKA-II and vitamin K1-epoxide . The protein C activity was significantly lower than that before the operation . High levels of more than 5 ng/ml of TAT were found before operation and after warfarin administration for 21 days . 2 ) Warfarin did not affect platelet aggregation , whereas ticlopidine inhibited ADP-induced platelet aggregation and aspirin inhibited both collagen-induced and arachidonic acid-induced aggregation . In conclusion , combined use of anticoagulants and antiplatelet agents after prosthetic valve replacement will suppress not only the blood coagulation but also the platelet aggregation systems OBJECTIVES The aim of the study was to test the value of low dose aspirin associated with st and ard oral anticoagulants ( OAC )  after mechanical mitral valve replacement ( MMRV ) to reduce str and s , thrombi and thromboembolic events . BACKGROUND Str and s and thrombi are thought to increase the risk of embolic events after MMVR , particularly in the immediate postoperative period . METHODS Two hundred twenty 
    Output:
    
agent
A lower daily dose of aspirin ( < 100 mg ) may be associated with a lower major bleeding risk than higher doses .
Adding antiplatelet therapy , either dipyridamole or low-dose aspirin , to oral anticoagulation decreases the risk of systemic embolism or death among patients with prosthetic heart valves .
The risk of major bleeding is increased with antiplatelet therapy .
These results apply to patients with mechanical prosthetic valves or those with biological valves and indicators of high risk such as atrial fibrillation or prior thromboembolic events .
The effectiveness and safety of low-dose aspirin ( 100 mg daily ) appears to be similar to higher-dose aspirin and dipyridamole .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Either dipyridamole , a vasodilator known to reduce platelate adhesiveness and aggregation , or a placebo was given in a daily dose of 400 mg as a r and om , blind trial to 70 patients who had undergone prosthetic cardiac-valve replacement . Patients in both groups were given anticoagulation with warfarin sodium . Of 36 patients in the placebo group followed for 557 months systemic arterial embolism occurred in 17 per cent . Twenty-seven patients in the dipyridamole group followed for 393 months gave no clinical evidence of arterial embolism .  Dipyridamole was discontinued shortly after surgery in seven patients , and these were followed for 110 months . In two of them cerebral emboli developed six months after treatment was discontinued . It is tentatively concluded that the addition of dipyridamole to a program of anticoagulation reduces the frequency of postoperative arterial emboli originating on prosthetic cardiac valves in patients who can tolerate the drug Authors studied the effect of coumarin , and its combination with low-dose ( 125 mg/day ) acetylsalicylic acid in the prevention of thromboembolic complication during a 10-year period ( average 4.7 years ) in a r and omized trial of 296 patients aged 18 - 60 year with tilting disc type prosthetic heart valve ( 159 mitral and 137 aortic ) in sinus rhythm . In the group treated with coumarin ( 152 patients , 743.4 patient-years ) 4 cases ( 2 of them fatal ) of valve thrombosis , 12 cases of peripheral embolism and 9 cases ( 3 intracranial , 3 among them fatal ) of major bleeding were observed ; in the group treated with coumarin plus acetylsalicylic acid ( 144 patients , 638.7 patient-years ) 2 cases ( 1 of them fatal ) of valve thrombosis , 4 cases of peripheral embolism and 14 cases ( 3 of them fatal ) of major bleeding were observed . In the case of valve thromboses the difference between the two groups was non-significant but still clinical ly remarkable ; peripheral embolism occurred in significantly higher number ( p < 0.05 ) . There was no statistically significant difference of bleeding complications between the two groups . The results suggest that the combination of coumarin plus low-dose acetylsalicylic acid is more effective in the prevention of thromboembolic complications in patients with mitral and aortic prosthetic heart valve than coumarin alone ; the danger of bleeding complications seems to be acceptable with adequate control Despite the use of oral anticoagulation in patients with prosthetic heart valves , persistent thromboembolism over time warrants a search for improved methods of prevention . Thus , patients receiving 1 or more mechanical prosthetic heart valves were r and omized to therapy with warfarin plus dipyridamole ( 400 mg/day ) or warfarin plus aspirin ( 500 mg/day ) on the basis of location and type of valve and surgeon , and followed up with a concurrent , nonr and omized control group taking warfarin alone . In 534 patients followed up 1,319 patient-years ,  excessive bleeding ( necessitating blood transfusion or hospitalization ) was noted in the warfarin plus aspirin group ( 23 of 170 [ 14 % ] , or 6.0/100 patient-years ) compared with warfarin plus dipyridamole ( 7 of 181 [ 4 % ] , or 1.6/100 patient-years , p less than 0.001 ) , or warfarin alone ( 9 of 183 [ 5 % ] , or 1.8/100 patient-years , p less than 0.001 ) . A trend was evident toward a reduction in thromboembolism in the warfarin plus dipyridamole group ( 2 of 181 [ 1 % ] , or 0.5/100 patient-years ) as compared with warfarin plus aspirin ( 7 of 170 [ 4 % ] , or 1.8/100 patient-years ) , or warfarin alone ( 6 of 183 [ 4 % ] , or 1.2/100 patient-years ) . Adequacy of anticoagulation ( based on 12,720 prothrombin time determinations ) was similar in all 3 groups with 65 % of prothrombin times in the therapeutic range ( 1.5 less than or equal to prothrombin time/control less than or equal to 2.5 ) , 30 % too low , and 5 % too high . Warfarin plus aspirin therapy result ed in excessive bleeding and is contraindicated . Longer follow-up study is needed to determine whether further separation of the incidence of thromboembolism can be detected BACKGROUND Mechanical heart valve replacement requires lifelong anticoagulant treatment . Aspirin has proved useful in further reducing thromboembolic events when added to oral anticoagulants . However , increased ( gastrointestinal ) bleeding was observed at the doses previously tested for this combination in heart valve prostheses . METHODS We performed a prospect i ve r and omized trial to compare the combination of low-intensity oral anticoagulants ( international normalized ratio 2.5 to 3.5 ) plus aspirin ( 100 mg/day ) ( arm A ) versus high-intensity oral anticoagulants alone ( arm B ) ( international normalized ratio 3.5 to 4.5 ) . Arm A included 258 patients and arm B 245 patients . The two groups were comparable for all baseline characteristics . RESULTS The outcomes of the study were embolism , valve thrombosis , and major hemorrhage . The median follow-up was 23 months . The two treatments offered similar antithrombotic protection . The incidence of embolic episodes was 1.32 per 100 patient-years ( 95 % confidence interval 0.53 to 2.7 ) for arm A and 1.48 per 100 patient-years ( 95 % confidence interval 0.59 to 3.03 ) for arm B. Major hemorrhage occurred in 1.13 per 100 patient-years ( 95 % confidence interval 0.41 to 2.45 ) for arm A and 2.33 per 100 patient-years ( 95 % confidence interval 1.17 to 4.14 ) for arm B. Gastrointestinal bleeding was not increased by this combined reduced dose of aspirin and coumarin OBJECTIVE Antiplatelet agents are used for prevention of thromboembolism in surgical patients and in patients with chronic atrial fibrillation . Up to date , however , results of r and omized studies comparing antiplatelet agents and oral anticoagulation have not been reported . The aim of this study was to compare the efficacy and safety of triflusal ( an antiplatelet agent ) versus acenocoumarol for primary prevention of thromboembolism in the early postoperative period after implantation of a bioprosthesis . METHODS In this prospect i ve , multicentric , r and omized , open pilot trial , patients were assigned to treatment with triflusal ( 600mg/d ) or acenocoumarol ( target INR 2.0 - 3.0 ) . Study medication was started 24 - 48h after valve replacement with a bioprosthesis , and continued for 3 months . Four follow-up visits were scheduled : baseline , and at 1 , 3 and 6 months thereafter . The primary end-point was a composite of the rate of thromboembolism , severe hemorrhage and valve-related mortality . RESULTS A total of 193 patients were included ( 97 received triflusal and 96 acenocoumarol ) , with a mean age of 72.5 years . Half were men . Aortic valve replacement was performed in 181 patients ( 93.8 % ) , mitral valve replacement in 10 patients ( 5.2 % ) and double valve replacement in 2 ( 1.0 % ) . Hospital mortality was 11 ( 5.7 % ) . Primary outcome was recorded in 9 patients with triflusal ( 9.4 % ) and in 10 patients with acenocoumarol ( 11 % ) . There were nine episodes ( 4.7 % ) of thromboembolism , six in the triflusal group and three in the acenocoumarol group , and three episodes of permanent neurological deficits , one in the triflusal group and two in the acenocoumarol group . Severe hemorrhage : nine episodes , six in the acenocoumarol group and three in the triflusal group . None of the observed differences in efficacy were statistically significant . Regarding safety , three patients in triflusal group reported at least one hemorrhage , compared to 10 in acenocoumarol group ( P=0.048 ) . CONCLUSIONS There were no significant differences in efficacy between both groups , however , triflusal showed a significantly lower incidence of bleeding episodes BACKGROUND Despite the use of warfarin , major systemic embolism remains an important complication in patients with heart-valve replacement . Although the addition of antiplatelet agents has the potential to reduce this complication , their efficacy and safety when given in combination with warfarin are uncertain . METHODS In a r and omized , double-blind , placebo-controlled trial , we assessed the efficacy and safety of adding aspirin ( 100 mg per day ) to warfarin treatment ( target international normalized ratio , 3.0 to 4.5 ) in 370 patients with mechanical heart valves or with tissue valves plus atrial fibrillation or a history of thromboembolism . RESULTS A total of 186 patients were r and omly assigned to aspirin  and 184 to placebo  , and they were followed for up to 4 years ( average , 2.5 ) . Major systemic embolism or death from vascular causes occurred in 6 aspirin-treated patients ( 1.9 percent per year ) and 24 placebo-treated patients ( 8.5 percent per year ) ( risk reduction with aspirin , 77 percent ; 95 percent confidence interval , 44 to 91 percent ; P < 0.001 ) . Major systemic embolism , nonfatal intracranial hemorrhage , or death from hemorrhage or vascular causes occurred in 12 patients assigned to aspirin ( 3.9 percent per year ) and 28 patients assigned to placebo ( 9.9 percent per year ) ( risk reduction , 61 per cent ; 95 percent confidence interval , 24 to 80 percent ; P = 0.005 ) ; major systemic embolism or death from any cause occurred in 13 patients ( 4.2 percent ) and 33 patients ( 11.7 percent ) , respectively ( risk reduction , 65 percent ; 95 percent confidence interval , 33 to 82 percent ; P < 0.001 ) ; and death from all causes occurred in 9 patients ( 2.8 percent ) and 22 patients ( 7.4 percent ) , respectively ( risk reduction , 63 percent ; 95 percent confidence interval , 19 to 83 percent ; P = 0.01 ) . Bleeding occurred in 71 patients in the aspirin group ( 35.0 percent ) , as compared with 49 patients in the placebo group ( 22.0 percent ) ( increase in risk , 55 percent ; 95 percent confidence interval , 8 to 124 percent ; P = 0.02 ) ; major bleeding occurred in 24 and 19 patients , respectively ( increase in risk , 27 percent ; 95 percent confidence interval , -30 to 132 percent ; P = 0.43 ) . CONCLUSIONS In patients with mechanical heart valves and high-risk patients with prosthetic tissue valves , the addition of aspirin to warfarin therapy reduced mortality , particularly mortality from vascular causes , together with major systemic embolism . Although there was some increase in bleeding , the risk of the combined treatment was more than offset by the considerable benefit Patients who had undergone prosthetic valve replacement were treated with warfarin ( anticoagulant ) alone or in combination of ticlopidine ( 200 mg/day ) or aspirin ( 81 mg/day ) ( anti-platelet agents ) . The study of blood coagulation factors and platelet aggregation were carried out with these cases . 1 ) The patients ( n = 24 ) receiving  warfarin for 21 days after prosthetic valve replacement revealed marked increases in PIVKA-II and vitamin K1-epoxide . The protein C activity was significantly lower than that before the operation . High levels of more than 5 ng/ml of TAT were found before operation and after warfarin administration for 21 days . 2 ) Warfarin did not affect platelet aggregation , whereas ticlopidine inhibited ADP-induced platelet aggregation and aspirin inhibited both collagen-induced and arachidonic acid-induced aggregation . In conclusion , combined use of anticoagulants and antiplatelet agents after prosthetic valve replacement will suppress not only the blood coagulation but also the platelet aggregation systems OBJECTIVES The aim of the study was to test the value of low dose aspirin associated with st and ard oral anticoagulants ( OAC )  after mechanical mitral valve replacement ( MMRV ) to reduce str and s , thrombi and thromboembolic events . BACKGROUND Str and s and thrombi are thought to increase the risk of embolic events after MMVR , particularly in the immediate postoperative period . METHODS Two hundred twenty 
    Output:
    