Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (TRAC): rationale and design for a prospective, randomized, co-operative trial. Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical prosthetic heart valves. Perioperative bridging therapy with unfractionated heparin or low-molecular-weight heparin in patients with mechanical prosthetic heart valves on long-term oral anticoagulants (from the REGIMEN Registry). [Significance of combined use of anticoagulants and antiplatelet agents in the early stage after prosthetic valve replacement]. Effectiveness of rivaroxaban for thromboprophylaxis of prosthetic heart valves in a porcine heterotopic valve model. Comparing Warfarin With Aspirin After Biological Aortic Valve Replacement: A Prospective Study Self-Management of Anticoagulant Therapy in Mechanical Heart Valve Patients: A Matched Cohort Study. High risk of thromboemboli early after bioprosthetic cardiac valve replacement. Dalteparin as Periprocedure Anticoagulation for Patients on Warfarin and at High Risk of Thrombosis Prevention of thromboembolism with ticlopidine shortly after valve repair or replacement with a bioprosthesis. Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (trac): prospective, randomized, co-operative trial. Postapproval Observational Studies of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation. Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: danger of aspirin compared with dipyridamole. Standardized Low–Molecular-Weight Heparin Bridging Regimen in Outpatients on Oral Anticoagulants Undergoing Invasive Procedure or Surgery: An Inception Cohort Management Study International normalized ratio self-management lowers the risk of thromboembolic events after prosthetic heart valve replacement. INR Self-Management Permits Lower Anticoagulation Levels After Mechanical Heart Valve Replacement Pharmacologic control of thromboembolic complications of cardiac-valve replacement. Postoperative hemostatic efficacy of gauze soaked in tranexamic acid, fibrin sponge, and dry gauze compression following dental extractions in anticoagulated patients with cardiovascular disease: a prospective, randomized study Low-dose acetyl salicylic acid versus oral anticoagulation after bioprosthetic aortic valve replacement. Final report of the ACTION registry. Anticoagulation in Patients with Mechanical Valves during Pregnancy Comparison of anticoagulation regimens after Carpentier-Edwards aortic or mitral valve replacement. Efficacy and safety of very low-dose self-management of oral anticoagulation in patients with mechanical heart valve replacement. International normalized ratio self-management after mechanical heart valve replacement: is an early start advantageous?
Antiplatelet agents are used for prevention of thromboembolism in surgical patients and in patients with chronic atrial fibrillation . However , up-to- date results of r and omized studies comparing antiplatelet agents and oral anticoagulation have not been reported . The aim of this study is to compare the efficacy and safety profile of triflusal versus acenocoumarol for primary prevention of thromboembolism in the early postoperative period after implantation of a bioprosthesis . This is a prospect i ve , multicentric , r and omized , open , pilot trial in which four acute-care teaching hospitals participate . Patients will be r and omly assigned to treatment with triflusal or acenocoumarol the day before valve replacement with a bioprosthesis . Primary outcome will be the combined endpoint of the rate of either thromboembolism or hemorrhage and valve-related mortality in each treatment group . Secondary outcomes will include the analysis of each of these rates separately together with permanent valve-related impairment according to the guidelines for reporting morbidity and mortality after cardiac valvular operations . A total of 200 patients will be recruited in a competitive manner ( 100 patients per arm ) over an 18-month period . The study will be completed in 2 years . Treatment assigned will be open to investigators and patients because of the need of blood monitoring and dosage adjustment in oral anticoagulant therapy . In order to minimize the bias , r and omization is central ly performed . The study medication will be given for 3 months being discontinued afterwards . Follow-up visits are scheduled at the time of patient 's inclusion in the study and at 1 , 3 , and 6 months thereafter . Homogeneity of groups will be analyzed using the Student 's t test , the Mann-Whitney U test , and the chi-square test , when appropriate . Rates of thromboembolism and hemorrhage will be calculated with the hazard function . In conclusion , antiplatelet treatment for patients undergoing valve replacement with a bioprosthesis is clinical ly relevant because of avoidance of inconveniences of oral anticoagulation ( monthly blood testing , dosage adjustment ) and decreased risk of bleeding . In case the results favor the use of antiplatelet drugs in these patients , this study will contribute to future development of strategies in the prevention of thromboembolism 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 Patients with mechanical prosthetic heart valves require long-term oral anticoagulant therapy ( OAT ) . During the temporary interruption of OAT , bridging anticoagulant therapy with unfractionated heparin ( UFH ) or low-molecular-weight heparin ( LMWH ) is recommended . This prespecified subgroup analysis from REGIMEN-a large , prospect i ve , multicenter registry-compared UFH  ( n = 73 ) and  LMWH  ( n = 172 ) as bridging anticoagulation in patients with mechanical heart valves on long-term OAT . Patient demographics and co-morbidities were generally similar between groups . There were more bileaflet valves in the LMWH group ( 67.4 % vs 43.8 % , p = 0.0005 ) , but no differences in valve positions between groups . The LMWH group was less likely to undergo major surgery ( 33.7 % vs 58.9 % , p = 0.0002 ) and cardiothoracic surgery ( 7.6 % vs 19.2 % , p = 0.008 ) , and to receive intraprocedural anticoagulants or thrombolytics  ( 4.1 % vs 13.7 % , p = 0.007 ) . Major adverse event rates ( 5.5 % vs 10.3 % , p = 0.23 ) and major bleeds ( 4.2 % vs 8.8 % , p = 0.17 ) were similar in the LMWH and UFH groups , respectively ; 1 arterial thromboembolic event occurred in each group . More LMWH-bridged patients were treated as out patients or discharged from the hospital in < 24 hours ( 68.6 % vs 6.8 % , p < 0.0001 ) . Multivariate logistic analysis found no significant differences in major bleeds and major composite adverse events when adjusting for cardiothoracic or major surgery between groups . In conclusion , for patients with mechanical prosthetic heart valves on long-term OAT , mostly outpatient-based LMWH bridging therapy appears to be feasible for selected procedures , is as safe as UFH , and is associated with a low arterial thromboembolic rate 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 Warfarin is used to reduce the risk of stroke and thromboembolic complications in patients with mechanical heart valves . Yet , despite frequent blood testing , its poor pharmacokinetic and pharmacodynamic profiles often result in variable therapeutic levels . Rivaroxaban is a direct competitive factor Xa inhibitor that is taken orally . It inhibits the active site of factor Xa without the need for the cofactor antithrombin , and thus , its mechanism of action is differentiated from that of the fractionated heparins and indirect factor Xa inhibitors . No in vivo data exist regarding the effectiveness of rivaroxaban in preventing thromboembolic complications of mechanical heart valves . We tested the hypothesis that rivaroxaban is as effective as enoxaparin for thromboprophylaxis of mechanical valves that use a previously described heterotopic aortic valve porcine model . METHODS A modified bileaflet mechanical valved conduit that bypassed the native , ligated descending thoracic aorta was implanted into 30 swine . Postoperatively , the animals were r and omly assigned to groups receiving no anticoagulation ( n = 10 ) , enoxaparin at 2 mg/kg subcutaneously twice daily ( n = 10 ) or rivaroxaban at 2 mg/kg orally twice daily ( n = 10 ) . The amount of valve thrombus was measured on post-implantation day 30 as the primary end point . Quantitative evaluation of radiolabelled platelet deposition on the valve prostheses was done and embolic and haemorrhagic events were measured as secondary end points . RESULTS Animals with no anticoagulation had a thrombus mean of 759.9 mg compared with 716.8 mg with enoxaparin treatment and 209.6 mg with rivaroxaban treatment ( P = 0.05 for enoxaparin vs rivaroxaban ) . Similarly , the mean number of platelets deposited on the valve prosthesis was lower in the rivaroxaban group ( 6.13 × 10(9 ) ) than in the enoxaparin group ( 3.03 × 10(10 ) ) ( P = 0.03 ) . CONCLUSIONS In this study , rivaroxaban was more effective than enoxaparin for short-term thromboprophylaxis of mechanical valve prosthetics in the heterotopic aortic position . It reduced valve thrombus and platelet deposition on day 30 following implantation without increased adverse events . Future studies would provide additional support for clinical trials evaluating rivaroxaban as an alternative to warfarin for appropriately selected patients with prosthetic aortic valves Background — Patients with prosthetic heart valves have a higher risk of developing valve thrombosis and arterial thromboembolism .  Antithrombotic therapy in the early postoperative period after biological aortic valve replacement ( BAVR ) is controversial . The American College of Cardiology/American Heart Association and European Society of Cardiology guidelines recommend the use of warfarin for the first 3 months after BAVR , although the American College Chest Physician guidelines suggest that the recommendations are very weak and that the risk/benefit is unclear . This prospect i ve study investigated the efficacy of postoperative warfarin compared with aspirin in patients after aortic valve replacement . Methods and Results — Patients undergoing BAVR between 2001 and 2002 received 2 antithrombotic therapies  : 141 patients received warfarin for the first 3 months , and 108 patients received only aspirin .  The major end points evaluated were the rate of cerebral ischemic events , bleeding , and survival . There were 3 and 5 postoperative cerebral ischemic events between 24 hours and 3 months for patients treated with aspirin and warfarin , respectively . After 3 months , the incidence of cerebral ischemic events did not differ between the 2 groups . The rate of major bleeding events , the stroke-free survival , and the overall survival rates were not statistically significant between the warfarin and aspirin groups . Conclusions —There seem to be no advantages in performing early anticoagulation therapy compared with a low-antiplatelet regimen with regard to early cerebral ischemic events , bleeding , and survival . Currently there is no evidence to support the fact that warfarin is more effective than aspirin BACKGROUND Patient-self-management ( PSM ) of oral anticoagulant therapy with vitamin K antagonists for mechanical heart valves has demonstrated efficacy in r and omized controlled trials . However , the effectiveness of PSM in clinical practice has only been investigated in small trials . Our aim was to evaluate the effectiveness of PSM of oral anticoagulant therapy in mechanical heart valve patients . METHODS We conducted a matched cohort study : cases were patients with a mechanical heart valve performing PSM affiliated with Aarhus University Hospital or Aalborg University Hospital , Denmark , in the period 1996 to 2012 ( n = 615 ) . Prospect ively registered patient data were obtained from data bases at two hospitals , and cross linkage between these data bases and national patient registries provided detailed information on comorbidities and events . Control patients were matched ( on sex , date of birth , year of first valve surgery , and grouped valve position ) in a ratio of 5:1 ( n = 3,075 ) with patients receiving  conventional management who were r and omly selected within the match group . The effectiveness and safety was estimated using major bleeding and thromboembolic events and death as outcomes . RESULTS We observed low event rates in the PSM group . After 5 years , PSM was associated with a lower risk of all-cause mortality compared with conventional management ( adjusted hazard ratio of 0.49 , 95 % confidence interval : 0.34 to 0.71 ) . The hazard ratios for thromboembolism and major bleeding were 0.91 ( 95 % confidence interval : 0.66 to 1.24 ) and 0.83 ( 95 % confidence interval : 0.56 to 1.22 ) . CONCLUSIONS Owing to superior clinical effectiveness , self-managed oral anticoagulant therapy may potentially improve the st and ard of care for patients with mechanical heart valves OBJECTIVES We studied the rate of thromboembolism in patients undergoing bioprosthetic replacement of the aortic or mitral valve , or both , at serial intervals after operation and the effects of anticoagulant or antiplatelet treatment  and risk factors . BACKGROUND Thromboembolism appears to occur early after operation , but the incidence , timing and risk factors for thromboembolism and the role , timing , adequacy , effectiveness , duration and risk of anticoagulation and antiplatelet agents are uncertain . METHODS The rate of thromboembolism was studied at three time intervals after operation ( 1 to 10 , 11 to 90 and > 90 days ) in 816 patients who underwent bioprosthetic replacement of the aortic or mitral valve , or both , at the Mayo Clinic from January 1975 to December 1982 . The effect of antithrombotic therapy ( warfarin , aspirin or dipyridamole , alone or in combination ) was evaluated . RESULTS Median follow-up of surviving patients was 8.6 years . The rate of thromboembolism ( % /year ) decreased significantly ( p < 0.01 ) at each time interval after operation ( 1 to 10 , 11 to 90 and > 90 days ) for mitral valve replacement ( 55 % , 10 % and 2.4%/year , respectively ) and over the first time interval for aortic valve replacement ( 41 % , 3.6 % and 1.9%/year , respectively ) . During the first 10 days , 52 % to 70 % of prothrombin time ratios were low ( < 1.5 x control ) . Patients with mitral valve replacement who received anticoagulation had a lower rate of thromboembolism for the entire follow-up period ( 2.5%/year with vs. 3.9%/year without anticoagulation , p = 0.05 ) . Of 112 patients with a first thromboembolic episode , permanent disability occurred in 38 % and death in 4 % . Risk factors for emboli were lack of anticoagulation , mitral valve location , history of thromboembolism and increasing age . Only 10 % of aortic , 44 % of mitral and 17 % of double valve recipients had anticoagulation at the time of an event . Patients with bleeding episodes ( 2.3%/year ) were older and usually underwent anticoagulation . Blood transfusions were required in 60 of 111 patients ( 1.2%/year ) , and 13 patients ( 0.3%/year ) died . CONCLUSIONS Thromboembolic risk was especially high for aortic and mitral valve replacement for 90 days after operation , and overall was increased with lack of anticoagulation , mitral valve location , previous thromboembolism and increasing age . Anticoagulation reduced thromboemboli and appears to be indicated in all patients as early as possible for 3 months and thereafter in those with risk factors , but needs prospect i ve testing BACKGROUND : Patients taking warfarin and at high risk for thromboembolic complications have traditionally been hospitalized for two to three days to receive st and ard treatment with intravenous heparin both prior to and following procedures while their international normalized ratio ( INR ) is subtherapeutic . OBJECTIVE : To assess the feasibility of protocol implementation for outpatient anticoagulation with low-molecular-weight heparin to eliminate or reduce the length of hospital admission needed solely for anticoagulation . METHODS : Patients included were receiving warfarin for a prosthetic heart valve , mitral valve disease with atrial fibrillation , or recent episode of venous thromboembolism .  Warfarin was discontinued four days prior to the procedure . Subcutaneous dalteparin 200 units/kg was given on the two mornings prior to the procedure and restarted 12–24 hours after the procedure until the INR was in the therapeutic range . Warfarin was reinitiated on the evening of surgery . RESULTS : Twenty-four patients underwent 26 procedures . There were two minor bleeding complications , and one patient experienced a transient ischemic attack . Patients received a median of five days of dalteparin . The INR returned to the therapeutic range on the median postoperative day 4 . All patients avoided two days of hospitalization prior to the procedure ( i.e. , no patients needed to be admitted preoperatively for anticoagulation ) . A median of four days would have been required for the sole purpose of postoperative anticoagulation . CONCLUSIONS : Outpatient perioperative anticoagulation with dalteparin for high-risk patients requiring long-term oral anticoagulation appears feasible and warrants further study BACKGROUND AND AIMS OF THE STUDY This study investigated the efficacy of postoperative ticlopidine as antiplatelet therapy in patients shortly after heart valve repair or replacement . METHODS Between 1990 and 1995 , 235 consecutive patients underwent either valve repair ( n = 67 ) or replacement with a bioprosthesis ( n = 168 ) . The bioprostheses used were Carpentier-Edwards porcine or pericardial ( n = 158 ) valves , Prima stentless valves ( n = 3 ) and cryopreserved homografts ( n = 7 ) . Types of repair were aortic ( one ) , mitral annuloplasty with Carpentier ring ( 65 ) and tricuspid repair ( one ) . Mean patient age was 67 ( range : 16 to 83 ) years for valve replacement and 57 ( range : 32 to 74 ) years for repair ( p < 0.01 ) .  Atrial fibrillation  occurred in 34 % of patients . The hospital mortality rate was 11 % ( 26 patients ) . Of the 209 survivors , 137 were assigned to antiplatelet treatment with ticlopidine for the first three months of follow up . The other 72 received either oral anticoagulation ( coumadin ; n = 40 ) , aspirin ( n = 14 ) or no medication ( n = 18 ) . In 15 patients , ticlopidine treatment was interrupted due to diarrhea ( 13 cases ) , mild allergic reaction ( one ) or anemia ( one ) . The mean follow up was 3.2 years ( range : 1 month to 6 years ) ; cumulative follow up was 684 patient-years ( pt-yr ) and was complete in 96 % of cases . RESULTS There were two episodes of thromboembolism in the ticlopidine group at 1 month and 6 months respectively , with a linearized incidence of 0.5 % pt-yr . In the coumadin group there were four episodes of thromboembolism , three within the first three months of follow up . The linearized incidence was 3 % pt-yr ( p < 0.01 ) . There were three episodes of hemorrhage in the ticlopidine group in the first three months of follow up and one in the coumadin group . The linearized incidence was 0.75 % pt-yr . CONCLUSIONS Following heart valve repair or replacement with a bioprosthesis , the first three months is a high-risk period for thromboembolism . Ticlopidine seems to prevent this complication better than conventional therapy with oral anticoagulants . Nevertheless , hemorrhage continues to be a problem with ticlopidine therapy 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 The pivotal r and omized clinical trials ( RCTs ) of non – vitamin K antagonist oral anticoagulants ( NOACs ) for stroke prevention in atrial fibrillation ( AF ) established the efficacy and safety of these drugs for patients with AF without mechanical prosthetic heart valves or significant ( rheumatic ) mitral valve stenosis.1 A clinical trial setting with strict inclusion and exclusion criteria was needed to obtain high- quality scientific evidence on the effects of NOACs compared with st and ard care ( ie , warfarin ) , but these results in highly selected trial cohorts may not be fully applicable to a diversity of patients or clinical circumstances encountered in daily practice 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 — Bridging therapy with low – molecular-weight heparin is usually recommended in patients who must stop oral anticoagulants before surgical or invasive procedures . To date , there is no universally accepted bridging regimen tailored to the patient ’s thromboembolic risk . This prospect i ve inception cohort management study was design ed to assess the efficacy and safety of an individualized bridging protocol applied to out patients . Methods and Results — Oral anticoagulants were stopped 5 days before the procedure . Low – molecular-weight heparin was started 3 to 4 days before surgery and continued for 6 days after surgery at 70 anti – factor Xa U/kg twice daily in high-thromboembolic-risk patients and prophylactic once-daily doses in moderate- to low-risk patients . Oral anticoagulation was resumed the day after the procedure with a boost dose of 50 % for 2 days and maintenance doses afterward . The patients were followed up for 30 days . Of the 1262 patients included in the study ( only 15 % had mechanical valves ) , 295 ( 23.4 % ) were high-thromboembolic-risk patients and 967 ( 76.6 % ) were moderate- to low-risk patients . In the intention-to-treat analysis , there were 5 thromboembolic events ( 0.4 % ; 95 % confidence interval , 0.1 to 0.9 ) , all in high-thromboembolic-risk patients . There were 15 major ( 1.2 % ; 95 % confidence interval , 0.7 to 2.0 ) and 53 minor ( 4.2 % ; 95 % confidence interval , 3.2 to 5.5 ) bleeding episodes . Major bleeding was associated with twice-daily low – molecular-weight heparin administration ( high-risk patients ) but not with the bleeding risk of the procedure . Conclusions — This management bridging protocol , tailored to patients ’ thromboembolic risk , appears to be feasible , effective , and safe for many patients , but safety in patients with mechanical prosthetic valves has not been conclusively established BACKGROUND Although prosthetic valves are durable and easy to implant , the need for lifetime warfarin-based anticoagulation restricts their exclusive usage . We investigated if anticoagulation self-management improves outcome in a single-center series . METHODS Between 1994 and 1998 , 765 patients with prosthetic valve replacements were prospect ively enrolled and r and omized to receive conventional anticoagulation management by their primary physician ( group 1 , n = 295 ) or to pursue anticoagulation self-management ( group 2 , n = 470 ) . A study head office was implemented to coordinate and monitor  anticoagulation protocol s ,  international normalized ratios ( INR ) , and  adverse events . Patients were instructed on how to obtain and test their own blood sample s and to adjust warfarin dosages according to the measured INR ( target range , 2.5 to 4 ) . RESULTS Mean INR values were slightly yet significantly smaller in group 1 than in group 2 ( 2.8 + /- 0.7 vs 3.0 + /- .6 , p < 0.001 ) . Moreover , INR values of patients with conventional INR management were frequently measured outside the INR target range , whereas those with anticoagulation self-management mostly remained within the range ( 35 % vs 21 % , p < 0.001 ) . In addition , the scatter of INR values was smaller if self-managed . Freedom from thromboembolism at 3 , 12 , and 24 months , respectively , was 99 % , 95 % , and 91 % in group 1 compared with 99 % , 98 % , and 96 % in group 2 ( p = 0.008 ) . Bleeding events were similar in both groups . Time-related multivariate analysis identified INR self-management and higher INR as independent predictors for better outcome . CONCLUSIONS Anticoagulation self-management can improve INR profiles up to 2 years after prosthetic valve replacement and reduce adverse events . Current indications of prosthetic rather than biologic valve implantations may be extended if the benefit of INR self-management is shown by future studies with longer follow-up Background —The Early Self Controlled Anticoagulation Trial ( ESCAT I ) showed that anticoagulation self-management after mechanical heart valve replacement decreased complication rates by maintaining INR levels closer to the target range than International Normalized Ratio ( INR ) home doctor management . The therapeutic range for the INR in that study was between 2.5 and 4.5 for all positions of prosthetic valves . ESCAT II should find out whether lowering the target range for INR self-management would further reduce complication rates . Methods —ESCAT II is a prospect i ve controlled r and omized ( valves : St. Jude Medical St and ard or Medtronic Hall , treatment : conventional/low-dose ) multicenter study with 3 300 patients . We present interim results of 1 818 patients . 908 were categorized as having a low-dose target range , which was INR 1.8 to 2.8 for prostheses in aortic position and 2.5 to 3.5 for prostheses in mitral position or in combined valve replacement . The control group ( conventional group ) with 910 patients aim ed at an INR of 2.5 to 4.5 for all valve positions . Results —In the conventional group , 74 % of INR values measured were within the therapeutic range . In the low-dose group , 72 % of the values were within that range . The linearized thromboembolism rate ( % per patient year ) was 0.21 % for both groups . The bleeding complication rate was 0.56 % in the low-dose regimen group versus 0.91 % in the conventional group . Conclusions —Early onset INR self-management under oral anticoagulation after mechanical heart valve replacement enables patients to keep within a lower and smaller INR target range . The reduced anticoagulation level result ed in fewer grade III bleeding complications without increasing thromboembolic event rates 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 Introduction Oral anticoagulants are widely prescribed drugs . Interruption of anticoagulant therapy prior to oral surgery has been an issue of great controversy . The purpose of this study was to evaluate the incidence of bleeding complications after dental extraction s in patients on anticoagulant therapy ( warfarin ) in whom different local hemostatic methods were used . Material and methods Patients using warfarin and requiring extraction s of at least two teeth were screened to participate in this prospect i ve , r and omized study . Extraction sites were considered as sampling units ( statistically representative sample size ) and were allocated to one of the three study groups ( G1—4.8 % tranexamic acid ; G2—fibrin sponge ; and G3—no local hemostatic agents ) . Results Eighty-four extraction sites were obtained from patients with mitral valve prolapse ( 47.4 % ) , prosthetic cardiac valve ( 23.7 % ) , venous thromboembolism ( 21.1 % ) , and pulmonary embolism ( 5.2 % ) .  International normalized ratio ( INR ) values ranged between 2.1 and 3.1 ( mean 2.51 ± 0.1 ) . Postoperative bleeding was observed in four surgical sites ( p < 0.001 ) and was mainly in older patients ( p = 0.005 ) . Discussion The three local hemostatic protocol s were similarly effective in controlling postoperative bleeding in patients undergoing anticoagulant therapy with warfarin .  The majority of teeth could be extracted with minimal problems in patients with cardiovascular diseases receiving treatment with anticoagulant therapy BACKGROUND The administration of antiplatelet agents versus anticoagulation after bioprosthetic aortic valve replacement ( AVR ) remains controversial . This study examined the safety and efficacy of anticoagulation with a vitamin-K antagonist ( VKA ) versus low-dose acetyl salicylic acid ( ASA ) , up to 6 months after bioprosthetic AVR . METHODS The ACTION Registry prospect ively collected data at 47 medical centers in Europe , Canada and India . The investigators were free to prescribe the postoperative antithrombotic regimen of their choice . Between January 2006 and June 2009 , 1118 patients underwent AVR alone or combined with coronary artery bypass graft ( CABG ) , of whom 500 received a VKA and 618 received ASA .  RESULTS Patients who received VKA had a higher prevalence of peripheral vascular disease , chronic renal insufficiency and coronary artery disease . At 180 days , 14 anticoagulated patients ( 2.8 % ) suffered a thromboembolism ( TE ) versus 9 patients ( 1.5 % ) treated with ASA ( P=0.12 ) and 18 anticoagulated patients ( 3.6 % ) suffered major bleeding ( MB ) versus 8 patients ( 1.3 % ) in the ASA group ( P=0.01 ) . MB or TE occurred in 31 patients ( 6 % ) treated with VKA versus 17 patients ( 2.8 % ) treated with ASA ( P=0.003 ) . By multiple variable analysis , preoperative cerebrovascular accident and peripheral vascular disease were strong predictors of postoperative TE , MB or both , in patients treated with VKA , though not in patients treated with ASA . CONCLUSIONS Compared with ASA , treatment with VKA was associated with higher morbidity within 6 months after bioprosthetic AVR , suggesting that , particularly after concomitant CABG surgery , recipients of bioprosthetic AVR should receive prophylactic ASA instead of VKA Mechanical valve thrombosis is a life-threatening event , while pregnancy is associated with a hypercoagulable state . Thus , in pregnant women with mechanical valves , adequate anticoagulation becomes even more critical . This prospect i ve study was conducted to establish a uniform anticoagulation regimen for these women . A total of 250 pregnancies in 245 women with mechanical heart valves were evaluated . The patients were divided into 2 groups : group 1 ( n = 150 ) took oral warfarin throughout pregnancy and group 2 ( n = 100 ) received subcutaneous heparin in the 1st trimester and oral warfarin for the other trimesters . Both groups received heparin at the time of delivery . There were no coumarin-induced fetal malformations . Minor thromboembolic episodes took place in 5 women in group 1 and 3 in group 2 . Valve thrombosis occurred in 1 woman in group 2 and led to 1 maternal death in this series . The incidence of spontaneous abortion was similar between the groups . We conclude that warfarin is safe and convenient to use during pregnancy . The teratogenic effects of warfarin during the 1st trimester are overstated , and switching to heparin is not m and atory BACKGROUND To identify the optimal use of anticoagulants after Carpentier-Edwards valve replacement , a retrospective study of all patients undergoing Carpentier-Edwards aortic ( N = 378 ) or mitral ( N = 370 ) valve replacement was done . METHODS AND RESULTS At the time of hospital discharge , 103 patients were managed with warfarin , 509 with aspirin alone , and 136 with no anticoagulation or antiplatelet therapy .  Over the first 90 days after aortic or mitral valve replacement , the linearized rate of hemorrhage was greater for warfarin than for aspirin or no therapy ( 16.7 + /- 7.6 % , 3.4 + /- 1.7 % , and 3.1 + /- 3.1 % per patient-year , respectively ; P = .03 ) . After aortic valve replacement , aspirin provided a low rate of thromboembolism ( 0.8 + /- 0.2 % per patient-year ) , not significantly different from warfarin or no treatment ( 2.9 + /- 1.6 % and 1.5 + /- 0.6 % per patient-year ) ( P = .07 ) . After mitral valve replacement , no single treatment was most advantageous because the rate of hemorrhage over the first 90 days for warfarin was equivalent to the 90-day rate of thromboembolism with aspirin or no therapy . CONCLUSIONS Anticoagulation after Carpentier-Edwards mitral valve replacement may be best guided by individual patient characteristics . Within the limits of a retrospective analysis , these data support the routine use of aspirin alone after Carpentier-Edwards aortic valve replacement , both in the first 90 days and long-term BACKGROUND Self-management improves oral anticoagulation control . Here we provide data of a preplanned interim analysis of very low-dose early self-controlled anticoagulation . METHODS In a prospect i ve , r and omized , multicenter trial , 1,137 patients performed low-dose international normalized ratio ( INR ) self-management with a target INR range of 1.8 . to 2.8 for aortic valve replacement recipients and 2.5 to 3.5 for mitral or double valve replacement recipients for the first six postoperative months . Thereafter , 379 patients continued to achieve the aforementioned INR target range ( LOW group ) , whereas the INR target value was set at 2.0 ( range , 1.6 to 2.1 ) for the remaining patients with aortic valve replacement and 2.3 ( range , 2.0 to 2.5 ) for the remaining patients with mitral valve or double valve replacement . One half of this latter group had to check their INR values once a week ( VL1 group ) the other half twice a week ( VL2 group ) . Patients were followed up for 24 months . RESULTS Beyond study month six , the incidence of thromboembolic events that required hospital admission was 0.58 % , 0.0 % , and 0.58 % in the LOW , VL1 , and VL2 groups , respectively ( p = 0.368 ) . The incidence of bleeding events per patient-year was 1.16 % , 1.07 % , and 0.58 % in the LOW , VL1 , and VL2 groups , respectively ( p = 0.665 ) . Mortality rate did not differ among study groups . CONCLUSIONS Data demonstrate the efficacy and safety of very low-dose INR self-management BACKGROUND Severe thromboembolic and hemorrhagic complications after mechanical heart valve replacement essentially depend on the intensity of oral anticoagulation and the fluctuation of individual international normalized ratio ( INR ) values . METHODS After heart valve replacement with Medtronic Hall , St. Jude Medical , and CarboMedics implants , patients were r and omly divided into two groups , one controlling INR values at home , the other being monitored by family practitioners . RESULTS Almost 80 % of the INR values recorded by patients at home were within the stipulated therapeutic range , INR 2.5 to 4.5 , compared with just 62 % of INR values recorded by family practitioners . The overall complication rate ( hemorrhages and thromboembolic events ) of the self-management group was significantly ( p < 0.05 ) decreased compared with the conventional group . CONCLUSIONS Through INR self-management , an improvement in the quality of ongoing oral anticoagulation could be shown . Starting this form of therapeutic control early after mechanical heart valve replacement appears to effect a further reduction in anticoagulant-induced complications
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 .
BACKGROUND Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism .
Oral anticoagulation alone , or the addition of antiplatelet drugs , has been used to minimise this risk .
An important issue is the effectiveness and safety of the latter strategy .
OBJECTIVES This is an up date of our previous review ; the goal was to create a valid synthesis of all available , method ologically sound data to further assess the safety and efficacy of combined oral anticoagulant and antiplatelet therapy versus oral anticoagulant monotherapy in patients with prosthetic heart valves .