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). Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (TRAC): rationale and design for a prospective, randomized, co-operative trial. Pharmacologic control of thromboembolic complications of cardiac-valve replacement. Strategy of continued vs interrupted novel oral anticoagulant at time of device surgery in patients with moderate to high risk of arterial thromboembolic events: The BRUISE CONTROL-2 trial. Anticoagulant and/or Antiplatelet Treatment in Patients with Atrial Fibrillation after Percutaneous Coronary Intervention Comparison of two antiplatelet therapy strategies in patients undergoing transcatheter aortic valve implantation. Self-Management of Anticoagulant Therapy in Mechanical Heart Valve Patients: A Matched Cohort Study. Thromboembolic stroke in patients with a HeartMate-II left ventricular assist device – the role of anticoagulation Efficacy and safety of percutaneous left atrial appendage closure to prevent thromboembolic events in atrial fibrillation patients with high stroke and bleeding risk [Significance of combined use of anticoagulants and antiplatelet agents in the early stage after prosthetic valve replacement]. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. Low-dose acetyl salicylic acid versus oral anticoagulation after bioprosthetic aortic valve replacement. Final report of the ACTION registry. Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non–vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH–AFNET 6) trial Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. Thrombelastographic hypercoagulability and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): a randomized controlled trial Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial.
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 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 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 BACKGROUND Patients who require perioperative anticoagulation during cardiac implantable electronic device surgery are at increased risk for bleeding complications . The BRUISE CONTROL trial demonstrated that continuing warfarin was safer than heparin bridging , reducing the incidence of clinical ly significant pocket hematoma . Novel oral anticoagulants are being increasingly prescribed in place of warfarin . The best perioperative management of these new anticoagulants is unknown . METHODS / DESIGN A r and omized controlled trial to investigate whether a strategy of continued vs interrupted novel oral anticoagulant ( dabigatran , rivaroxaban , or apixaban ) at the time of device surgery , in patients with moderate to high risk of arterial thromboembolic events , reduces the incidence of clinical ly significant hematoma ( defined as a hematoma requiring reoperation and /or result ing in prolongation of hospitalization , and /or requiring interruption of anticoagulation ) . The secondary outcomes include components of the primary outcome , composite of all other major perioperative bleeding events , thromboembolic events , all-cause mortality , cost-effectiveness , patient quality of life , perioperative pain , and satisfaction . Planned analyses include descriptive statistics of all baseline variables . For the primary outcome , interrupted vs continued novel oral anticoagulant arms will be compared using the χ(2 ) test . If any clinical ly significant differences are identified , a logistic regression analysis will be conducted . Quality of life will be assessed using EuroQol-5D , and perioperative pain using a visual analog scale . DISCUSSION BRUISE CONTROL-2 is a r and omized trial evaluating the best strategy to manage novel oral anticoagulants at the time of device surgery . We hypothesize that device surgery can be performed safely without interruption of these medications Background : Atrial fibrillation ( AF ) is the most common cardiac arrhythmia sustained and frequently occurs in patients with coronary heart disease . Thus , a large number of patients requiring percutaneous coronary intervention ( PCI  ) also suffer from AF . An anticoagulant regimen has not been st and ardized for patients with AF after coronary stent implantation . Patients and Methods : The authors investigated data from 159 patients with AF who underwent PCI in their department . Baseline variables and incidence of a combined endpoint ( stroke , myocardial infa rct ion , cardiovascular death , severe bleeding ) were compared in patients receiving clopidogrel and acetylsalicylic acid ( ASA ; group 1 ) versus patients receiving the combination of clopidogrel and ASA with low-molecular-weight heparin ( LMWH ; group 2 ) versus patients receiving the combination of clopidogrel and ASA with oral anticoagulation ( OAC ; group 3 )  at discharge . Results : Patients discharged with triple therapy including OAC seemed to be at higher risk : patients in group 3 had decreased left ventricular ejection fraction and increased inflammatory state as measured by plasma fibrinogen and C-reactive protein . Moreover , previous OAC treatment and strokes were found more often in this subgroup of patients . In a median follow-up of 1.4 years , two severe bleeding events ( both in group 1 ) , four myocardial infa rct ions ( all in group 1 ) , 13 strokes ( nine in group 1 , four in group 2 ) , and nine cardiovascular deaths ( three in group 1 , five in group 2 , one in group 3 ) occurred . Conclusion : In this analysis , no treatment regimen seemed to be clearly superior . It underlines the importance of prospect i ve , r and omized trials to investigate the optimal antithrombotic/antiplatelet treatment for patients with AF after PCI.ZusammenfassungHintergrund : Vorhofflimmern ( VHF ) ist die häufigste Herzrhythmusstörung und wichtige Komorbidität bei Patienten mit koronarer Herzkrankheit . Welche antithrombotische/antithrombozytäre Therapiestrategie bei Patienten mit Vorhofflimmern nach perkutaner Koronarintervention ( PCI ) verfolgt werden sollte , ist aktuell nicht eindeutig zu beantworten . Patienten und Method ik : Die Autoren identifizierten retrospektiv 159 Patienten mit VHF , die in ihrer Abteilung in den Jahren 1999–2004 eine PCI erhalten hatten . Die Grunderkrankungen und die Inzidenz eines kombinierten Endpunkts ( Schlaganfall , Myokardinfarkt , kardiovaskulär bedingter Tod , schwere Blutung ) wurden bei Patienten verglichen , die Clopidogrel und Acetylsalicylsäure ( ASS ; Gruppe 1 ) , Clopidogrel und ASS in Kombination mit niedermolekularem Heparin ( Gruppe 2 ) sowie Clopidogrel und ASS und zusätzlich orale Antikoagulation erhalten hatten ( Gruppe 3).Ergebnisse : Die Grunderkrankungen der Patienten in den drei Gruppen waren nicht signifikant unterschiedlich . In einem medianen Beobachtungszeitraum von 1,4 Jahren konnten zwei schwere Blutungen ( in Gruppe 1 ) , vier Myokardinfarkte ( in Gruppe 1 ) , 13 Schlaganfälle ( neun in Gruppe 1 , vier in Gruppe 2 ) und neun kardiovaskulär bedingte Todesfälle ( drei in Gruppe 1 , fünf in Gruppe 2 , einer in Gruppe 3 ) nachgewiesen werden . Schlussfolgerung : In dieser Untersuchung erwies sich keine Therapiestrategie einer and eren gegenüber als eindeutig überlegen . Die erhobenen Date n zeigen , wie wichtig es ist , prospektive , r and omisierte Studien bezüglich der antithrombotischen/antithrombozytären Therapie durchzuführen , um Patienten mit AF nach PCI optimal beh and eln zu können Dual antiplatelet therapy is commonly used in patients undergoing transcatheter aortic valve implantation ( TAVI ) , but the optimal antiplatelet regimen is uncertain and remains to be determined . The objective of this study was to compare 2 strategies of antiplatelet therapy in patients undergoing TAVI . A strategy using monoantiplatelet therapy  ( group A , n = 164 ) was prospect ively compared with a strategy using  dual antiplatelet therapy ( group B , n = 128 ) in 292 consecutive patients undergoing TAVI .  The primary end point was a combination of mortality , major stroke , life-threatening bleeding ( LTB ) , myocardial infa rct ion , and major vascular complications at 30 days . All adverse events were adjudicated according to the Valve Academic Research Consortium . The primary end point occurred in 22 patients ( 13.4 % ) in the group A and in 30 patients ( 23.4 % ) in the group B ( hazard ratio 0.51 , 95 % confidence interval 0.28 to 0.94 , p = 0.026 ) . LTB ( 3.7 % vs 12.5 % , p = 0.005 ) and major bleedings ( 2.4 % vs 13.3 % , p < 0.0001 ) occurred less frequently in the group A , whereas the incidence of stroke ( 1.2 % vs 4.7 % , p = 0.14 ) and myocardial infa rct ion ( 1.2 % vs 0.8 % , p = 1.0 ) was not significantly different between the 2 groups . The benefit of a strategy using mono versus dual antiplatelet therapy persisted after multivariate adjustment and propensity score analysis ( hazard ratio 0.53 , 95 % confidence interval 0.28 to 0.95 , p = 0.033 ) . In conclusion , a strategy using mono versus dual antiplatelet therapy in patients undergoing TAVI reduces LTB and major bleedings without increasing the risk of stroke and myocardial infa rct ion . The results of our study question the justification of dual antiplatelet therapy and require confirmation in a r and omized trial 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 Background and purpose It is unknown what the optimal anticoagulant level is to prevent thromboembolic stroke in patients with left ventricular assist device ( LVAD ) support . We aim ed to evaluate the relation between coagulation status and the occurrence of thromboembolic stroke in HeartMate-II LVAD assisted patients . Methods Thirty-eight consecutive patients with a HeartMate-II LVAD were included . Coagulation status was classified according to INR and aPTT ratio at : 1 ) the moment of first thromboembolic stroke ; and 2 ) during the two weeks preceding the first thromboembolic stroke to assess long-term coagulation status . In patients without stroke , coagulation status was determined just before heart transplant , VAD explantation or death , whichever came first , and at two weeks preceding these surrogate endpoints . Based on coagulation status , patients were divided in two groups : Group I ( reference group ) was defined as INR below 2 and aPTT ratio below 1.5 ; Group II ( adequate anticoagulation ) as INR above 2 or aPTT ratio above 1.5 . Logistic regression analysis was performed to assess the odds ratio for developing stroke for patients with adequate anticoagulation compared to the reference Group . Results Thromboembolic stroke occurred in six ( 16 % ) patients , none within 2 weeks after LVAD implantation . Considering coagulation status at the time of event , patients in coagulation Group II had no decreased risk for thromboembolic stroke ( OR 0.78 ; 95 % CI 0.12–5.0 ) . Results for coagulation status 2 weeks prior of event could not be calculated as all six strokes occurred in Group II . Conclusion In our experience anticoagulation within predefined targets is not associated with a reduced thromboembolic stroke risk in patients with a HeartMate-II LVAD on antiplatelet therapy . However , no firm statement about the effect of either anticoagulant or antiaggregant therapy can be made based on our study . A larger r and omized study is needed to support the hypothesis that there may be no additional benefit of coumarin or heparin therapy compared with antiplatelet therapy alone Aims The r and omized PROTECT AF trial demonstrated non-inferiority of left atrial appendage ( LAA ) closure to oral anticoagulation with warfarin . Current guidelines give a class IIb recommendation for LAA closure . We evaluated the efficacy and safety of LAA closure in a consecutive series of non-valvular atrial fibrillation patients with contraindications to long-term oral anticoagulation or at high bleeding risk . Methods and results 101 consecutive non-valvular atrial fibrillation patients ( age 74.7 ± 7.5 years ) at high risk for stroke ( CHA2DS2-VASc Score 4.4 ± 1.6 ) and high bleeding risk ( HAS-BLED Score 4.2 ± 1.3 ) received LAA closure with either the Watchman closure device ( n = 38 ) or the Amplatzer cardiac plug ( n = 63 ) . Dual antiplatelet therapy with aspirin and clopidogrel was recommended for 3–6 months after device implantation , followed by long-term antiplatelet therapy with aspirin . No anticoagulation was given after device implantation . Mean follow-up was 400 days . One patient ( 1 % ) experienced a transient ischemic attack , and two patients ( 2 % ) suffered from ischemic stroke . While on recommended antiplatelet therapy , bleeding occurred in 12/101 patients ( 12 % ) . Bleeding was significantly reduced with 3 compared with 6 months dual antiplatelet therapy ( 3.0 vs. 16.2 % , p < 0.05 ) while ischemic or thrombotic events were similar . Conclusion Left atrial appendage closure in patients with non-valvular atrial fibrillation and high risk for stroke and bleeding events effectively prevented stroke and reduced cerebral ischemic events compared to expected stroke rate according to CHA2DS2-VASc Score . Dual antiplatelet therapy for 3 months reduced the rate of bleeding events compared to 6 months therapy with no increase of thrombotic events 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 This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis . BACKGROUND Warfarin was more effective than aspirin in preventing stroke in these patients ; combined therapy with low anticoagulant intensity was ineffective . Mitral stenosis patients were not investigated . METHODS We performed a multicenter r and omized trial in 1,209 patients at risk . The intermediate-risk group included patients with risk factors or age > 60 years : 242 received the cyclooxygenase inhibitor triflusal  , 237 received  acenocumarol , and 235 received a combination of both .  The high-risk group included patients with prior embolism or mitral stenosis : 259 received anticoagulants and 236 received the combined therapy . Median follow-up was 2.76 years . Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism . RESULTS Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- ( hazard ratio [ HR ] 0.33 [ 95 % confidence interval (CI)0.12 to 0.91 ] ; p = 0.02 ) and the high-risk group ( HR 0.51 [ 95 % CI 0.27 to 0.96 ] ; p = 0.03 ) . Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group . Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy . CONCLUSIONS The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients 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 Background Oral anticoagulation prevents ischemic strokes in patients with atrial fibrillation ( AF ) . Early detection of AF and subsequent initiation of oral anticoagulation help to prevent strokes in AF patients . Implanted cardiac pacemakers and defibrillators allow seamless detection of atrial high rate episodes ( AHRE ) , but the best antithrombotic therapy in patients with AHRE is not known . Rationale Stroke risk is higher in pacemaker patients with AHRE than in those without , but the available data also show that stroke risk in patients with AHRE is lower than in patients with AF . Furthermore , only a minority of patients with AHRE will develop AF , many strokes occur without a temporal relation to AHRE , and AHRE can reflect other arrhythmias than AF or artifacts . An adequately powered controlled trial of oral anticoagulation in patients with AHRE is needed . Design The Non – vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes ( NOAH – AFNET 6 ) trial tests whether oral anticoagulation with edoxaban is superior to prevent the primary efficacy outcome of stroke or cardiovascular death compared with aspirin or no antithrombotic therapy based on evidence ‐based indications . The primary safety outcome will be major bleeding . NOAH – AFNET 6 will r and omize 3,400 patients with AHRE , but without documented AF , aged ≥65 years with at least 1 other stroke risk factor , to oral anticoagulation therapy ( edoxaban ) or no anticoagulation . All patients will be followed until the end of this investigator‐driven , prospect i ve , parallel‐group , r and omized , event‐driven , double‐blind , multicenter phase IIIb trial . Patients will be censored when they develop AF and offered open‐label anticoagulation . The sponsor is the Atrial Fibrillation NETwork ( AFNET ) . The trial is supported by the DZHK ( German Centre for Cardiovascular Research ) , the BMBF ( German Ministry of Education and Research ) , and Daiichi Sankyo Europe . Conclusion NOAH – AFNET 6 will provide robust information on the effect of oral anticoagulation in patients with atrial high rate episodes detected by implanted devices . Graphical abstract Figure . No Caption available BACKGROUND Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infa rct ion , stroke , and death from cardiovascular causes . Antiplatelet drugs reduce this risk , but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear . METHODS We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent ( target international normalized ratio [ INR ] , 2.0 to 3.0 ) or to antiplatelet therapy alone . The first co primary outcome was myocardial infa rct ion , stroke , or death from cardiovascular causes ; the second co primary outcome was myocardial infa rct ion , stroke , severe ischemia of the peripheral or coronary arteries leading to urgent intervention , or death from cardiovascular causes . RESULTS A total of 2161 patients were r and omly assigned to therapy . The mean follow-up time was 35 months . Myocardial infa rct ion , stroke , or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy ( 12.2 % ) and in 144 of 1081 patients receiving antiplatelet therapy alone ( 13.3 % ) ( relative risk , 0.92 ; 95 % confidence interval [ CI ] , 0.73 to 1.16 ; P=0.48 ) . Myocardial infa rct ion , stroke , severe ischemia , or death from cardiovascular causes occurred in 172 patients receiving combination therapy ( 15.9 % ) as compared with 188 patients receiving antiplatelet therapy alone ( 17.4 % ) ( relative risk , 0.91 ; 95 % CI , 0.74 to 1.12 ; P=0.37 ) . Life-threatening bleeding occurred in 43 patients receiving combination therapy ( 4.0 % ) as compared with 13 patients receiving antiplatelet therapy alone ( 1.2 % ) ( relative risk , 3.41 ; 95 % CI , 1.84 to 6.35 ; P<0.001 ) . CONCLUSIONS In patients with peripheral arterial disease , the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding . ( Clinical Trials.gov number , NCT00125671 [ Clinical Trials.gov ] . ) Abstract A hypercoagulable state has , in observational studies , been associated with increased risk of thromboembolic events . The aim of this trial was to study whether dual antiplatelet therapy ( DAPT ) with clopidogrel in addition to aspirin could reduce the rate of graft occlusions , thromboembolic events , and death compared to aspirin monotherapy in hypercoagulable patients undergoing coronary artery bypass surgery . A total of 1683 patients were screened for eligibility , among which 165 patients were r and omized and 133 patients underwent multislice computed tomography scan to evaluate their grafts .  Thrombelastography ( TEG ) and multiplate aggregometry  were performed before and after surgery , and again at three months follow up . TEG hypercoagulability was defined as the maximum amplitude above 69 mm . At three months follow up , 17 out of 66 ( 25.7 % ) DAPT patients and 15 of 67 ( 22.4 % ) aspirin patients had significant graft stenosis or occlusions ( p = 0.839 ) . Saphenous vein grafts ( SVGs ) were stenosed or occluded in 15 ( 22.7 % ) patients in the DAPT group and 7 ( 10.4 % ) in the aspirin group ( p = 0.167 ) . Thromboembolic events and death after the second postoperative day ( when clopidogrel was started ) were numerically , but not statistically , lower in the DAPT group , 3 ( 3.8 % ) vs. 8 ( 9.9 % ) , p = 0.211 . In univariate logistic regression analysis , only postoperative day 4 platelet response to aspirin measured with multiplate was correlated with graft occlusion , OR 1.020 [ 1.002–1.039 ] , p = 0.033 . This is the first trial to test the hypothesis of intensified antiplatelet therapy in hypercoagulable patients . Due to the low enrollment and high loss to follow up , our results can only be viewed as hypothesis generating . We found a high rate of graft occlusions in this patient population . Our results were not suggestive of that DAPT improved saphenous vein graft patency . A trend was observed in patients on DAPT toward fewer MI and deaths . Postoperative response to aspirin therapy was found to be associated with early SVG occlusion After cardiac valve replacement patients were blindly r and omized into two groups , both receiving aspirin ( 330 mg ) and dipyridamole ( 75 mg ) twice daily and the oral anticoagulant acenocoumarol ( Sintrom ) . An international normalized ratio of 2.0 to 2.99 was assigned to group A and 3.0 to 4.5 to group B ; both groups were subsequently analyzed for thromboembolic and hemorrhagic complications .  Final evaluation included 51 and 48 patients , respectively . The follow-up was 626 months for group A ( 12.3 months/patient ) and 486 months for group B ( 10.1 months/patient ) . The frequency of thromboembolism was equal in both groups : one transient ischemic attack in group A ( a rate of 1.92/100 patient-years ) and two transient ischemic attacks in group B ( a rate of 4.94/100 patient-years ) . There was , however , a statistical difference in bleeding complications between the two groups ( p less than 0.02 ) . Two patients bled in group A , a rate of 3.9 % ( 3.8/100 patient-years ) , which represents an incidence of one episode each 25.6 years of treatment ; 10 patients bled in group B , a rate of 20.8 % ( 24.7/100 patient-years ) representing an incidence of one episode each 4 years of treatment . We conclude that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to 4.5 and confers good protection from thromboembolism when oral anticoagulant therapy is used conjointly with platelet function-inhibiting drugs in patients with mechanical substitute heart valves BACKGROUND Oral anticoagulation ( OAC ) is the recommended therapy for patients with atrial fibrillation ( AF ) because it reduces the risk of stroke and other thromboembolic events . Dual antiplatelet therapy ( DAPT ) is required after percutaneous coronary intervention and stenting ( PCI-S ) . In patients with AF requiring PCI-S  , the association of DAPT and OAC carries an increased risk of bleeding , whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events . OBJECTIVE The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy ( TT ) in patients with nonvalvular AF at low-to-moderate risk of stroke ( CHADS2 score ≤2 ) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications . DESIGN The MUSICA-2 is a multicenter , open-label r and omized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S.  The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events : death , myocardial infa rct ion , stent thrombosis , or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients . CONCLUSIONS The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic 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 .