Safety of continuous anticoagulation with dabigatran during implantation of cardiac rhythm devices. 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. Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF): study protocol for a randomised controlled trial Anticoagulation therapy for the prevention of hemodialysis tunneled cuffed catheter (TCC) thrombosis Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. Evaluation of the safety and efficacy of an edoxaban‐based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST‐AF PCI trial Outcome of patients on oral anticoagulation undergoing coronary artery stenting: data from discharge to 12 months in the Warfarin and Coronary Stenting (WAR-STENT) Registry. Antithrombotic therapy in elderly patients with atrial fibrillation: effects and bleeding complications: a stratified analysis of the NASPEAF randomized trial. [Study of combined anticoagulant (fluindione)-aspirin therapy in patients with atrial fibrillation at high risk for thromboembolic complications. A randomized trial (FFAACS)]. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review Anticoagulant therapy in cerebral infarction Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. Platelet activation is a preoperative risk factor for the development of thromboembolic complications in patients with continuous‐flow left ventricular assist device Antithrombotic management and 1-year outcome of patients on oral anticoagulation undergoing coronary stent implantation (from the Registro Regionale Angioplastiche Emilia-Romagna Registry). The Long-Term Clinical Course of Acute Deep Venous Thrombosis Trial Protocol: A randomised controlled trial of extended anticoagulation treatment versus routine anticoagulation treatment for the prevention of recurrent VTE and post thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (The ExACT Study) [A longitudinal study on left atrial thrombosis in patients with non-rheumatic atrial fibrillation treated with anticoagulants]. Rationale and design of MANJUSRI trial: a randomized, open-label, active-controlled multicenter study to evaluate the safety of combined therapy with ticagrelor and warfarin in AF subjects after PCI-eS. Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly. close: Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence: Study design Rationale and design of the dual antiplatelet therapy study, a prospective, multicenter, randomized, double-blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary intervention with either drug-eluting stent  Self-management of oral anticoagulation reduces major outcomes in the elderly. A randomized controlled trial.
The perioperative bleeding risk associated with therapeutic anticoagulation at cardiac implantable electronic device implantation has previously been demonstrated to vary by the specific anticoagulant used . Although uninterrupted anticoagulation with warfarin appears to be safe , heparin products have been shown to increase the risk of perioperative bleeding . However , the risk associated with cardiac implantable electronic device implantation with anticoagulation using dabigatran , a novel oral direct thrombin inhibitor , is not known . We performed a prospect i ve observational study of patients receiving dabigatran for anticoagulation who underwent cardiac implantable electronic device implantation from June 2011 through May 2012 . The study end points included thromboembolic and bleeding complications within 30 days of surgery . Major bleeding complications were defined as bleeding requiring surgical intervention , prolongation of hospitalization , and discontinuation of the anticoagulant or transfusion of blood products within 30 days of surgery . Minor bleeding complications included the development of a hematoma not requiring additional intervention . The thrombotic end points included stroke , transient ischemic attack , myocardial infa rct ion , pulmonary embolism , and deep vein thrombosis .  A total of 25 patients were identified for inclusion . During the index hospitalization , no thromboembolic or bleeding complications developed . No major bleeding complications occurred within 30 days of surgery . One minor bleeding event ( 4 % ) occurred within 30 days of surgery in 1 patient who was also receiving dual antiplatelet therapy . In conclusion , although no thromboembolic or major bleeding events were observed , additional studies are required to define the optimal antithrombotic management in the perioperative period 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 Background There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage during treatment with oral anticoagulation .  These patients are currently treated with oral anticoagulants , antiplatelet drugs , or no antithrombotic treatment , depending on personal and institutional preferences . Compared with warfarin , the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism , intracranial haemorrhage , and case fatality in patients with atrial fibrillation . Compared with aspirin , apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation , and has a similar risk of intracerebral haemorrhage . Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage . To inform a phase III trial , the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation ( APACHE-AF ) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided . Methods / Design APACHE-AF is a phase II , multicentre , open-label , parallel-group , r and omised clinical trial with masked outcome assessment . One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherl and s . These patients will be r and omly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation . Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician . The primary outcome is the composite of vascular death or non-fatal stroke during follow-up . We aim to include 100 patients in 2.5 years . All patients will be followed-up for the duration of the study , but at least for 1 year . Recruitment commenced in September 2014 and is ongoing . This trial is funded by the Dutch Heart Foundation ( 2012 T077 ) and ZonMW (015008048).Trial registration NTR4526 ( 16 April 2014 ) Background Chronic oral anticoagulation is currently used to avoid thrombosis and the malfunction of tunneled cuffed catheters ( TCCs ) for hemodialysis ( HD ) . The aim of the study was to assess the efficacy of early warfarin administration , after TCC placement , in comparison to its administration after the first thrombosis or malfunction event of the TCC . Patients and methods One hundred and forty-four chronic dialysis patients , who underwent TCC placement between June 2001 and June 2005 , were r and omized into two groups : 81 patients , group A , started oral anticoagulation 12 hr after the TCC placement ( target international normalized ratio ( INR ) 1.8–2.5 ) , in association with ticlopidine 250 mg/die ; 63 patients , group B , started warfarin after the first thrombosis/malfunction episode ( target INR 1.8–2.5 ) in association with ticlopidine 250 mg/die . The efficacy of oral anticoagulation therapy in preventing TCC thrombotic complications was evaluated in a 12-month follow-up period , after TCC placement , in terms of : a ) the number of patients with thrombotic-malfunction events ; b ) the number of thrombotic-malfunction events with urokinase infusion ( events/patient/year ) ; c ) intradialytic blood flow rate ( BFR , ml/min ) ; d ) negative blood pressure ( BP ) from the arterial line of the TCC ( AP , mmHg ) ; e ) positive BP , in the extracorporeal circuit from the venous line ( VP , mmHg ) ; and f ) bleeding complications . Results Ten patients ( 12 % ) in group A showed TCC thrombosis/malfunction vs. 33 patients ( 52 % ) in group B ( p<0.01 ) . In group A , 0.16 events of thrombosis/malfunction per patient/year vs. 1.65 in group B ( p<0.001 ) were observed . BFR was respectively 305 ± 34 vs. 246 ± 42 ml/min ( p<0.001 ) . AP was –124 ± 13 in group A vs. –174 ± 21 mmHg in group B ( p<0.05 ) . VP was 112 ± 28 in group A vs. 168 ± 41 mmHg in group B ( p<0.05 ) . No patient showed any bleeding events .  Conclusions Early warfarin therapy allows a significant reduction in TCC thrombotic complications and an improvement in both arterial and venous fluxes in comparison with the same therapy administered after the first TCC thrombotic/malfunction event . This therapy did not induce any bleeding complications in the patients included in the study BACKGROUND The placement of stents in coronary arteries has been shown to reduce restenosis in comparison to balloon angioplasty . However , clinical use of intracoronary stents is impeded by the risk of subacute stent thrombosis and complications associated with the anticoagulant regimen . To reduce these complications , the hypothesis that systemic anticoagulation is not necessary when adequate stent expansion is achieved was prospect ively evaluated on a consecutive series of patients who received intracoronary stents .  METHODS AND RESULTS From March 1993 to January 1994 , 359 patients underwent Palmaz-Schatz coronary stent insertion .  After an initial successful angiographic result with < 20 % stenosis by visual estimation had been achieved , intravascular ultrasound imaging was performed . Further balloon dilatation of the stent was guided by observation of the intravascular ultrasound images . All patients with adequate stent expansion confirmed by ultrasound were treated only with antiplatelet therapy ( either ticlopidine for 1 month with short-term aspirin for 5 days or only aspirin ) after the procedure . Clinical success ( procedure success without early postprocedural events ) at 2 months was achieved in 338 patients ( 94 % ) . With an inflation pressure of 14.9 + /- 3.0 atm and a balloon-to-vessel ratio of 1.17 + /- 0.19 , optimal stent expansion was achieved in 321 of the 334 patients ( 96 % ) who underwent intravascular ultrasound evaluation , with these patients receiving only antiplatelet therapy after the procedure . Despite the absence of anticoagulation , there were only two acute stent thromboses ( 0.6 % ) and one subacute stent thrombosis ( 0.3 % ) at 2-month clinical follow-up . Follow-up angiography at 3 to 6 months documented two additional occlusions ( 0.6 % ) at the stent site . At 6-month clinical follow-up , angiographically documented stent occlusion had occurred in 5 patients ( 1.6 % ) . At 6-month clinical follow-up , there was a 5.7 % incidence of myocardial infa rct ion , a 6.4 % rate of coronary bypass surgery , and a 1.9 % incidence of death . Emergency intervention ( emergency angioplasty or bailout stent ) for a stent thrombosis event was performed in 3 patients ( 0.8 % ) . The overall event rate was relatively high because of intraprocedural complications that occurred in 16 patients ( 4.5 % ) . Intraprocedural complications , however , decreased to 1 % when angiographically appropriately sized balloons were used for final stent dilations . There was one ischemic vascular complication that occurred at the time of the procedure and one ischemic vascular complication that occurred at the time of angiographic follow-up . By 6 months , repeat angioplasty for symptomatic restenosis was performed in 47 patients ( 13.1 % ) . CONCLUSIONS The Palmaz-Schatz stent can be safely inserted in coronary arteries without subsequent anticoagulation provided that stent expansion is adequate and there are no other flow-limiting lesions present . The use of high-pressure final balloon dilatations and confirmation of adequate stent expansion by intravascular ultrasound provide assurance that anticoagulation therapy can be safely omitted . This technique significantly reduces hospital time and vascular complications and has a low stent thrombosis rate Background The optimal antithrombotic treatment after percutaneous coronary intervention ( PCI ) with stenting in patients with atrial fibrillation ( AF ) is unknown . In the ENGAGE AF‐TIMI 48 trial , edoxaban was noninferior to a vitamin K antagonist ( VKA ) with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and cardiovascular death in patients with nonvalvular AF . The effects of edoxaban in combination with single‐ or dual‐antiplatelet therapy in the setting of PCI are unexplored . Design The ENTRUST‐AF PCI trial is a multinational , multicenter , r and omized , open‐label phase 3b trial with blinded end point evaluation involving 1,500 patients on oral anticoagulation for AF . Patients are r and omized between 4 hours and 5 days after successful PCI to either an edoxaban‐based strategy ( experimental arm ; 60 mg [ or 30 mg according to dose reduction criteria ] once daily plus a P2Y12 antagonist [ default clopidogrel , 75 mg once daily ] for 12 months ) or a VKA‐based strategy ( control arm ; VKA plus a P2Y12 antagonist [ as above ] plus acetylsalicylic acid [ 100 mg once daily ] for 30 days to 12 months ) . The primary safety end point is the incidence of International Society on Thrombosis and Haemostasis – defined major or clinical ly relevant nonmajor bleeding . The main efficacy end point is the composite of cardiovascular death , stroke , systemic embolic events , spontaneous myocardial infa rct ion , and definite stent thrombosis . Summary The ENTRUST‐AF PCI trial tests the hypothesis that an edoxaban‐based antithrombotic strategy reduces the risk of bleeding complications after PCI compared with VKA plus conventional dual‐antiplatelet therapy in patients with AF in need of oral anticoagulation . The relative risk of ischemic events between groups will be compared OBJECTIVES To obtain further , and more focused , information on the efficacy and safety of the antithrombotic regimens , including triple therapy ( TT ) of warfarin , aspirin , and clopidogrel ; dual therapy ( DT ) of warfarin and single antiplatelet agent ( aspirin or clopidogrel ) ; and dual-antiplatelet therapy ( DAPT ) of aspirin and clopidogrel , prescribed to patients on oral anticoagulation ( OAC ) undergoing percutaneous coronary intervention with stent ( PCI-S ) . BACKGROUND The true efficacy and safety of TT , DT , and DAPT in OAC patients undergoing PCI-S is largely undefined . METHODS We analyzed the data base of the prospect i ve , multicenter WARfarin and coronary STENTing ( WAR-STENT ) registry ( Clinical Trials.gov identifier NCT00722319 ) , only including the post-discharge period . RESULTS Of the 401 patients discharged alive from index hospitalization , 339 ( 85 % ) , 20 ( 5 % ) , and 42 ( 10 % ) were prescribed TT , DT , and DAPT , respectively . Throughout a mean follow-up of 368.3 ± 22.8 days , major adverse cardiovascular events ( MACE ) ( including cardiovascular death , myocardial infa rct ion , repeat revascularization , stent thrombosis , and thromboembolism ) , total bleeding , major bleeding , and combination of MACE plus total bleeding were comparable across the three treatment groups . The absolute rate of major bleeding with TT was 4 % . The antithrombotic treatment actually ongoing at major bleeding was TT in 44 % , DT in 50 % , and DAPT in 6 % of cases . CONCLUSION In the real-world population of OAC patients undergoing PCI-S in the WAR-STENT registry , the three antithrombotic regimens of TT , DT , and DAPT showed comparable efficacy and safety . Due to several limitations , our data can not be considered conclusive in confuting the current recommendations to prescribe TT . Further properly design ed and sized studies are warranted AIMS Atrial fibrillation patients with prior embolism have a high risk of vascular events in spite of anticoagulant therapy and elderly patients carry an additional risk . We analysed and compared vascular events-rate between older and younger than 75 years atrial fibrillation patients r and omized to anticoagulant-alone or combined antiplatelet plus moderate-level anticoagulant therapy . METHODS AND RESULTS A total of 967 patients stratified by age and the history of prior embolism were r and omized to therapeutic doses of anticoagulant-alone or combined antithrombotic therapy . Primary events were fatal and non-fatal ischaemic or haemorrhagic stroke/transient ischaemic attack , systemic embolism and myocardial infa rct ion , sudden death and death from bleeding . The elderly , compared with the younger patients , had higher event-rate [ hazard ratio 2.31 ( 95 % confidence interval 1.37 - 3.90 ) , P < 0.003 ] . The elderly suffered higher severe bleeding event-rate during anticoagulant therapy . The combined , compared with the anticoagulant therapy , reduced the vascular events-rate in the elderly ( P = 0.012 ) and caused less intracranial haemorrhages and less bleeding mortality , although more non-fatal gastric bleeding . CONCLUSION The elderly with AF had a higher event-rate than the younger patients . A higher severe bleeding event-rate was also registered in elderly patients receiving anticoagulant therapy .  Combined , compared with anticoagulant therapy , significantly reduced vascular events and bleeding mortality in elderly patients BACKGROUND A combination of low-dose aspirin ( A ) and anticoagulation ( AC ) may provide better protection against thromboembolic events compared with AC alone in high-risk patients with atrial fibrillation ( AF ) . METHODS We performed a multicentric placebo-controlled double blind-trial to test the preventive efficacy against thromboembolic events of the addition of aspirin ( A ) ( 100 mg ) or placebo ( P ) to anticoagulant treatment in patients with high-risk atrial fibrillation . A total of 157 patients were included , with atrial fibrillation and previous thromboembolic event or older than 65 years with either a history of hypertension , a recent episode of heart failure or a left ventricular dysfunction . All patients received fluindione ( F ) and P or F and A , with an INR target between 2 and 2.6 . The primary endpoint was a combined endpoint of stroke ( ischaemic or haemorrhagic ) , myocardial infa rct ion , systemic arterial emboli or vascular death . RESULTS The study had to be stopped prematurely owing to a too low recruitment rate . During follow-up ( 0.84 years ) 3 non-fatal thromboembolic events were recorded ( 1P , 2A ) and 6 patients died ( 3P , 3A ) , none of them from a thromboembolic complication . However , 3 deaths were secondary to severe haemorrhagic complications ( 1P , 2A ) . Non-fatal haemorrhagic complications occurred more often in group A ( n = 10 , 13.1 pour cent ) compared with group P ( n = 1 , 1.2 pour cent ) , p = 0.003 . CONCLUSION The FFAACS study was not able to show any therapeutic benefit from the addition of aspirin to anticoagulant in patients with high-risk AF . Such a combination increased the incidence rate of bleeding complications , which therefore greatly reduces its potential overall benefit BACKGROUND Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications , yet the benefits and risks of treatment beyond 1 year are uncertain . METHODS Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed . After 12 months of treatment with a thienopyridine drug ( clopidogrel or prasugrel ) and aspirin , patients were r and omly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months ; all patients continued receiving aspirin . The co primary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events ( a composite of death , myocardial infa rct ion , or stroke ) during the period from 12 to 30 months . The primary safety end point was moderate or severe bleeding . RESULTS A total of 9961 patients were r and omly assigned to continue thienopyridine treatment or to receive placebo . Continued treatment with thienopyridine , as compared with placebo , reduced the rates of stent thrombosis ( 0.4 % vs. 1.4 % ; hazard ratio , 0.29 [ 95 % confidence interval { CI } , 0.17 to 0.48 ] ; P<0.001 ) and major adverse cardiovascular and cerebrovascular events ( 4.3 % vs. 5.9 % ; hazard ratio , 0.71 [ 95 % CI , 0.59 to 0.85 ] ; P<0.001 ) . The rate of myocardial infa rct ion was lower with thienopyridine treatment than with placebo ( 2.1 % vs. 4.1 % ; hazard ratio , 0.47 ; P<0.001 ) . The rate of death from any cause was 2.0 % in the group that continued thienopyridine therapy and 1.5 % in the placebo group ( hazard ratio , 1.36 [ 95 % CI , 1.00 to 1.85 ] ; P=0.05 ) . The rate of moderate or severe bleeding was increased with continued thienopyridine treatment ( 2.5 % vs. 1.6 % , P=0.001 ) . An elevated risk of stent thrombosis and myocardial infa rct ion was observed in both groups during the 3 months after discontinuation of thienopyridine treatment . CONCLUSIONS Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent , as compared with aspirin therapy alone , significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding . ( Funded by a consortium of eight device and drug manufacturers and others ; DAPT Clinical Trials.gov number , NCT00977938 . ) Background Many national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease ( CVD ) should no longer be based on BP level alone , but on absolute cardiovascular risk . While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP , clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain “ untreated ” . Objective We aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals ( 45 - 65 years ) with mildly elevated BP ( systolic BP 140 - 159 mmHg and /or diastolic BP 90 - 99 mmHg ) stratified by absolute risk for primary prevention of CVD , but particularly in the low-risk ( < 10 % five-year absolute risk ) group . Methods R and omized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process . First , r and omized trials of BP-lowering therapy will be identified by ( 1 ) retrieving the references of trials included in published systematic review s of BP-lowering therapy , ( 2 ) retrieving studies published by the Blood Pressure Lowering Treatment Trialists ’ Collaboration ( BPLTTC ) , and ( 3 ) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memor and um on BP management . Posttrial follow-up studies will then be identified by forward citation search ing the r and omized trials identified in step 1 through Web of Science . The search will include r and omized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase . Age is the major determinant of absolute cardiovascular risk , so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile . The primary outcome will be all-cause mortality . Secondary outcomes will include cardiovascular mortality , fatal stroke , fatal myocardial infa rct ion , and death due to heart failure . Results The search es for existing systematic review s and BPLTTC studies were piloted and modified . The study is expected to be completed before June 2018 . Conclusions The findings of this study will contribute to the body of knowledge concerning the beneficial , neutral , or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk . Trial Registration PROSPERO International Prospect i ve Register of Systematic Review s : CRD42017058414 ; https://www.crd.york.ac.uk/ PROSPERO /display_record.asp?ID = CRD42017058414 ( Archived by WebCite ® at http://www.webcitation.org/6t6sa8O2Q IN A PREVIOUS issue of this journa1,l the details of our national cooperative ControIled study of long-term anticoagulant therapy in cerebral ischemia and cerebral infa rct ion were presented along with an interim report covering some eighteen months . At that time , longterm anticoagulation did not appear to reduce the mortality and there was an added risk due to hemorrhagic complications . The study , embracing 7 clinical centers and extending over a period of forty-two months , was brought to an end in August 1961 , and this is a report of our findings and final conclusions . The important aspects of the study , including selection and classification of cases and method of anticoagulation , were fully covered previously and will not be repeated here . A total of 443 patients were enrolled in the study , each patient being assigned to the anticoagulant or nonanticoagulant therapeutic groups on a statistically r and om basis by means of sealed envelopes . All the patients in the study were divided into 5 diagnostic categories : ( 1 ) transient ischemic attacks , ( 2 ) thrombosis-in-evolution , ( 3 ) thrombosis-completed stroke , ( 4 ) thorem ( thrombosis or embolism ) , and ( 5 ) cerebral embolism . Analysis of the control and treated groups showed that they were remarkably comparable in most respects ( table 1 ) . The number of cases involving the internal carotidmiddle cerebral and vertebral-basilar systems varied from category to category ; in the whole series there were 328 in the carotid and 102 in the vertebral-basilar . In regard to blood pressure , 59.6 per cent of the entire group had an elevated blood pressure . To determine the effect of anticoagulant therapy , the cases were analyzed as to the incidence of ( 1 ) deaths , ( 2 ) progression of cerebral infa rct ion due to either extension of the infa rct ed area or a new infa rct ion , ( 3 ) the advent of extracerebral thrombotic episodes ( ECTE ) , including myocardial infa rct ion , pulmonary embolism , thrombophlebitis , and so forth , and ( 4 ) hemorrhagic complications . Patients whose anticoagulants were stopped within two weeks of death when the patient 's condition was deteriorating were reckoned as deaths while on anticoagulants 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 ] . ) AIMS To correlate the dynamics of platelet activation with the development of thromboembolic events in patients with continuous-flow left ventricular assist device ( cf-LVAD ) . METHODS AND RESULTS The  platelet activity state ( PAS ) assay  was utilized to evaluate platelet activation in 68 cf-LVAD patients implanted with the HeartMate II ( n = 15 , 22 % ) , HeartMate 3 ( n = 15 , 22 % ) , or HeartWare HVAD ( n = 38 , 56 % ) .  PAS  was measured preoperatively , early post-implant , and at long-term follow-up ( 1 , 3 , 6 , 12 , 18 , and 24 months post-implant ) .  PAS  was also measured at the occurrence of adverse events in patients who developed thrombotic complications . Data on patient demographics , medical history , antithrombotic therapy , and coagulation parameters were also analysed . Over a median follow-up of 602 ( 234 - 942 ) days , PAS values did not increase over time in the overall population ( P = 0.15 ) . However , PAS measured at event was 15-fold higher in the six patients ( 9 % ) who suffered pump thrombosis ( n = 2 ) or ischaemic stroke ( n = 4 ) vs. the rest of the population [ 6.67 % ( 5.59%-11.98 % ) vs. 0.45 % ( 0.33%-0.75 % ) ; P = 0.012 ] , despite comparable coagulation profile . Pre-implant PAS values were 4.5-fold higher in these patients [ 1.90 % ( 1.24%-3.17 % ) vs. 0.42 % ( 0.32%-0.72 % ) ; P = 0.006 ] . Neither preoperative variables nor the type of the pump or the antiplatelet strategy were associated with a higher risk of complications . CONCLUSIONS Thrombotic events are associated with altered PAS values . Moreover , baseline elevated PAS values in patients who developed thrombotic events suggest patient-specific tendency to post-implant thromboembolic complications . Prospect ively , systematic monitoring of PAS might guide the development of refined patient-tailored antithrombotic strategies and the technological improvement of LVAD design Current recommendations for the antithrombotic management of patients receiving oral anticoagulation ( OAC ) who undergo percutaneous coronary intervention with stent implantation ( PCI-S ) are based on limited and relatively weak data . To broaden and strengthen available evidence , the management and 1-year outcomes of OAC patients who underwent PCI-S and were included in a prospect i ve , multicenter registry from 2003 to 2007 were evaluated . Among the 632 patients receiving OAC , mostly because of atrial fibrillation ( 58 % ) , who underwent PCI-S , mostly because of acute coronary syndromes ( 63 % ) , dual-antiplatelet therapy with aspirin and clopidogrel was the most frequently prescribed at discharge ( 48 % ) , followed by triple therapy with OAC , aspirin , and clopidogrel ( 32 % ) and OAC plus aspirin ( 18 % ) . The choice of antithrombotic therapy largely matched the thromboembolic risk profiles of patients , with the prescription of regimens including OAC predicted by the presence of non-low-risk features . The cumulative 1-year occurrence of major adverse cardiovascular events was as high as 27 % and was not significantly different among the 3 treatment groups . Stroke and stent thrombosis were limited to 2 % and 3 % , respectively , and although no significant differences were found among the 3 groups , stroke was 4 times less frequent when OAC , with either 1 or 2 antiplatelet agents , was administered . Major bleeding was also limited to 3 % , with no significant differences among the 3 groups . In conclusion , these findings suggest overall real-world management of OAC patients who undergo PCI-S  that is in accordance with their clinical risk profiles and give further support to the reported efficacy and safety of triple therapy for the optimal treatment of these patients Deep venous thrombosis of the lower extremity is a serious disorder ; the estimated incidence is 1 per 1000 persons per year [ 1 - 3 ] . The disease can occur after surgical procedures and trauma and in the presence of cancer or inherited coagulation disorders ; it can also develop without any of these factors [ 3 ] . The clinical course of deep venous thrombosis might be complicated by pulmonary embolism , recurrent episodes of deep venous thrombosis , and the development of serious post-thrombotic sequelae , such as venous ulceration , debilitating pain , and intractable edema [ 3 ] . Patients with deep venous thrombosis are usually treated with an initial course of heparin ( 5 to 10 days ) followed by 3 to 6 months of oral anticoagulant therapy . This treatment regimen reduces the risk for short-term thromboembolic complications to approximately 5 % [ 4 , 5 ] . The long-term risk for recurrent venous thromboembolism and the incidence and severity of post-thrombotic sequelae in patients with symptomatic deep venous thrombosis have not been well documented . In a recent large r and omized , clinical trial comparing 6 weeks of oral anticoagulant therapy with 6 months of therapy [ 6 ] , patients with symptomatic deep venous thrombosis were followed for 2 years for recurrences and death . This trial showed a substantial reduction in the risk for recurrent venous thromboembolism among patients in the 6-month oral anticoagulant group , but the investigators did not report on the occurrence of the post-thrombotic syndrome . Another recent study [ 7 ] reported the 8-year incidence of recurrences and post-thrombotic manifestations in patients with confirmed symptomatic deep venous thrombosis . However , only a few patients were included in this study , and data were collected retrospectively . We assessed the clinical course of a first episode of symptomatic deep venous thrombosis in a large consecutive series of patients who had long-term follow-up . We assessed mortality and the long-term incidences of recurrent venous thromboembolism and the post-thrombotic syndrome . We also evaluated the potential risk factors for these three outcomes . Methods Identification of Inception Cohort The Department of Internal Medicine of the University of Padua , Padua , Italy , is a diagnostic facility for out patients with clinical ly suspected venous thromboembolism in a community of approximately 350 000 persons . All consecutive out patients with a first episode of clinical ly suspected deep venous thrombosis who were referred by their general practitioners between January 1986 and December 1991 had noninvasive testing [ 8 ] . Patients were potentially eligible for the study if confirmatory venography showed deep venous thrombosis . Patients were excluded from the study if they had been referred because of recurrent venous thrombosis , were geographically inaccessible for follow-up , or refused to give informed consent . The Institutional Review Board of the hospital of the University of Padua approved the study . Baseline Assessment At the time of referral , demographic characteristics were recorded and a medical history was taken ; information was elicited on the period between the onset of symptoms and presentation to the thrombosis service ( patientphysician delay ) , the presence of risk factors for thrombosis ( that is , cancer , surgery , trauma or fracture , immobilization for more than 7 days , pregnancy or childbirth , or estrogen use ) , and symptoms of pulmonary embolism . Information was also obtained on the history of venous thromboembolism in first-degree relatives .  Antithrombin , protein C and S , and lupus-like anticoagulant levels were subsequently measured . Assays were done , and previously described criteria for abnormality and deficiency were used [ 9 ] . The venograms obtained at baseline were divided into those representing proximal venous thrombosis ( with or without concurrent venous thrombosis of the calf ) and those indicating isolated venous thrombosis of the calf . Proximal venous thrombosis was defined as thrombosis located above the trifurcation of the calf veins that involved at least the popliteal vein , superficial femoral vein , common femoral vein , or iliac vein . The location and occlusiveness of proximal thrombi were also determined . A patient was considered to have nonocclusive deep venous thrombosis if contrast material was seen between the thrombus and the vessel wall along the entire thrombus . Treatment Patients were admitted to the hospital and treated with an initial course of high-dose intravenous st and ard heparin ( a bolus of 5000 U followed by continuous infusion of 30 000 U/d , subsequently adjusted to maintain an activated partial thromboplastin time between 1.5 and 2.5 times the normal value ) or subcutaneous low-molecular-weight heparin ( 90 U of anti-factor Xa/kg of body weight twice daily ) . Therapy with oral anticoagulant agents ( warfarin ) was started on day 5 to 7 of treatment and was continued for 3 months . The oral anticoagulant dose was adjusted daily to maintain an international normalized ratio between 2.0 and 3.0 . Treatment with low-molecular-weight heparin was discontinued on day 10 or later if the international normalized ratio was less than 2.0 . This treatment strategy deviated in the following groups of patients : those with cancer , protein deficiencies , or lupus anticoagulant , in whom oral anticoagulation therapy was prolonged ; those with small isolated venous thrombosis of the calf , who received oral anticoagulation alone ; those with contraindications to anticoagulant treatment , who received no treatment or an inferior caval-vein filter ; those who refused to be hospitalized , who received low-dose heparin and oral anticoagulant agents ; and those with threatened viability of the leg , who received thrombolytic therapy .  The actual type and duration of treatments were recorded . All patients were instructed to wear elastic graduated compression stockings ( providing 40 mm Hg of pressure at the ankle ) for at least 2 years . Follow-up All patients were seen 3 and 6 months after the initial referral and thereafter returned to the study center every 6 months for follow-up assessment s. Patients were asked to return to the thrombosis center immediately if symptoms suggestive of recurrent venous thromboembolism developed . Follow-up was continued for as long as 8 years or until July 1995 . To avoid diagnostic suspicion bias , the medical history on general health , symptoms of recurrent venous thromboembolism , and the post-thrombotic syndrome was obtained by using a st and ardized form . Patients who could not attend the follow-up sessions were visited at home . For all patients who died during follow-up , the date and cause of death were documented . Diagnosis of Recurrent Venous Thromboembolism and Hemorrhage Contrast venography of the symptomatic leg or legs was done as described previously [ 10 ] . The criteria for deep venous thrombosis were a constant intraluminal filling defect confirmed in at least two different projections or nonvisualization of a vein or a segment thereof , despite adequate technique and repeated injections with contrast material . The presence or absence of venous thrombosis was assessed by a panel of independent observers who were unaware of the patient 's other clinical features or previous test results . If a patient presented with clinical ly suspected recurrent venous thrombosis of the leg , venography was done . The criterion for recurrent venous thrombosis of the leg was a new intraluminal filling defect on the venogram . If the venogram was not diagnostic , recurrent venous thrombosis was diagnosed on the basis of an abnormal 125I-fibrinogen leg scan or results of noninvasive tests that had changed from normal to abnormal [ 11 , 12 ] . Patients with suspected pulmonary embolism had venography if they had concurrent leg symptoms or perfusion lung scanning in the absence of leg symptoms . Pulmonary embolism was excluded if the perfusion scan was normal . Because ventilation lung scanning was not available during the first years of the study and because pulmonary angiography could not routinely be done , we could not definitively diagnose pulmonary embolism in some patients . If a definitive diagnosis could not be made , patients were classified as not having recurrent venous thromboembolism . Perfusion lung scanning and pulmonary angiography were done and their results were interpreted according to st and ard procedures [ 13 ] . Hemorrhagic episodes were classified as major or minor , as reported previously [ 14 ] . The documentation of all patients suspected of having a recurrent venous thromboembolic or bleeding event was review ed by a three-member adjudication committee that was unaware of further clinical details of the patient . Criteria for the Post-Thrombotic Syndrome Presence of the post-thrombotic syndrome was assessed by investigators who were unaware of previous post-thrombotic manifestations and further clinical details of the patient . The presence of leg symptoms ( pain , cramps , heaviness , pruritus , and paresthesia ) and signs ( pretibial edema , in duration of the skin , hyperpigmentation , new venous ectasia , redness , and pain during calf compression ) was scored . For each item , the investigators assigned a score of 0 ( not present or minimal ) to 3 ( severe ) . The presence of a venous ulcer of the lower limb was recorded . In patients with bilateral thrombosis , the higher score was used . A total score of 15 or more on two consecutive visits or the presence of a venous ulcer indicated severe post-thrombotic syndrome , and a total score of 5 to 14 on two consecutive visits indicated mild post-thrombotic syndrome . This score has been shown to have good reproducibility , and it correlates well with the patient 's perception of the interference of leg symptoms with daily life [ 15 ] . Statistical Analysis We calculated Kaplan-Meier estimates and 95 % CIs for a visual assessment of survival and calculated the risk for recurrent venous thromboembolism and mild and severe Background Venous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity . The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot . However , the recurrence rate following a deep vein thrombosis remains approximately 10 % per annum following treatment cessation irrespective of the duration of anticoagulation therapy . Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence . Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration . It has a cumulative incidence after 2 years of around 25 % and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure . Methods / design Patients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and r and omly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis . At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device . In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study . Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life question naires . Discussion The primary aim of the study is to investigate whether extending oral anticoagulation treatment ( prior to discontinuing treatment ) beyond 3–6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence . The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels  prior to discontinuing treatment and identify the potential of D-dimer point of care testing for identification of high risk patients within a primary care setting .Trial registration IS RCT BACKGROUND Although atrial thrombosis is common in patients with non-rheumatic atrial fibrillation ( NRAF ) ( 6 - 27 % ) , there are no studies about the effect that anticoagulant or antiplatelet drugs have on it . AIM OF THE STUDY We have investigated the role of anticoagulant therapy , followed by family physicians , on left atrial thrombosis detected via transesophageal echocardiography ( TEE ) in patients with NRAF . METHODS Sixty patients enrolled in the TASAF ( Trieste Area Study on non-rheumatic Atrial Fibrillation ) ( 60 % males , mean age 72 + /- 7 years , 17 % with lone atrial fibrillation , duration of arrhythmia 111 + /- 79 months ) , in whom we found a left atrial and /or left atrial appendage thrombus via TEE , were anticoagulated .  The thrombus was in the left atrial appendage in 57 patients and in the left atrium in the others . In 28 of them it was mobile and in 50 , the left atrial appendage flow was low or absent . Lastly , in 46 patients we found  spontaneous echocontrast  and a bilobate appendage was present in 8 of them . At follow-up , we repeated the TEE to evaluate the effect of the therapy on the atrial thrombosis . RESULTS Only 53 patients received anticoagulant therapy  ( 45 correctly ) , while 7 were treated with antiplatelet drugs by their family physicians . After a mean follow-up of 16 months , all patients underwent a repeat TEE and the thrombus was no longer evident in 35 cases ( 58 % ) . The thrombosis disappeared in 26 ( 58 % ) of the 45 patients who correctly took anticoagulant therapy and in 5 of the 8 who were not adequately anticoagulated . Moreover , we did n't observe the thrombus in 4 of the 7 patients who were treated with antiplatelet drugs . There was no significant statistical difference between the benefits of anticoagulants and antiplatelet therapy in dissolving left atrial thrombosis . During follow-up , we recorded only one embolic event in the retina . None of the patients on antiplatelet drugs complained of any side effects , whereas in 5 of the 53 on anticoagulant therapy , we recorded one fatal intracranial hemorrhage , one gastric hemorrhage and three minor complications . CONCLUSIONS Left atrial thrombosis in NRAF disappears in anticoagulated patients in an high percentage of cases ( the therapy probably acts on more recent thrombi ) . Moreover , this therapy decreases the incidence of embolic events , although it increases the risk of hemorrages . Since the management of this preventive treatment in general medicine is very difficult , we hope that our health organization will establish Anticoagulation Clinics for the central ized management of this therapy BACKGROUND Long-term oral anticoagulant treatment is obligatory in patients with atrial fibrillation ( AF , score of CHA₂DS₂VASc≥2 ) . When these patients undergo  percutaneous coronary intervention with a drug-eluting stent ( PCI-eS ) , there is also an indication for aspirin and clopidogrel treatment , according to the ESC Guidelines . However , triple therapy has been known to increase the risk of bleeding complications . Unfortunately , there is little prospect i ve data available to resolve this issue . Therefore , it is imperative that an optimal therapy for AF patients with indications of both anticoagulation and antiplatelet intervention to prevent thrombotic complications without increasing the risk of bleeding is found . OBJECTIVES This prospect i ve , r and omized , multicenter study is going to assess the hypothesis that in persistent or permanent AF patients ( score of CHA₂DS₂VASc≥2 ) after PCI-eS , the combination therapy of oral anticoagulation ( warfarin ) and ticagrelor ( 90 mg/bid ) could reduce the risk of bleeding events . DESIGN A multicenter , active-controlled , open-label , r and omized trial is to be performed to evaluate dual antithrombotic therapy ( ticagrelor+warfarin ) in persistent or permanent AF patients ( score of CHA₂DS₂VASc≥2 ) after PCI-eS versus the combination of triple antithrombosis ( clopidogrel+aspirin+warfarin ) . The primary endpoint is the overall bleeding up to 6 months , according to TIMI criteria and classifications . The secondary endpoints are the major bleeding events up to 6 months , according to TIMI criteria . The sample size is estimated at 296 . CONCLUSION This study is intended to provide information about the safety characteristics  of warfarin and ticagrelor in persistent or permanent AF patients after PCI-eS. No prospect i ve r and omized study has been conducted on the issue of antithrombotic therapy using warfarin and ticagrelor in these patients . Therefore , the MANJUSRI trial will help to explore and determine a new potential therapeutic regimen for AF patients after PCI-eS. TRIAL REGISTRATION Clinical Trials.gov # NCT02206815 , registered July 30 , 2014 BACKGROUND In 1989 , the European Working Party on High Blood Pressure in the Elderly started the double-blind , placebo-controlled , Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension . This report addresses whether the benefit of antihypertensive treatment varied according to sex , previous cardiovascular complications , age , initial blood pressure ( BP ) , and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per- protocol analysis . METHODS After stratification for center , sex , and cardiovascular complications , 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were r and omized . Active treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) and /or hydrochlorothiazide ( 12.5 - 25 mg/d ) , titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg , to below 150 mm Hg . In the control group , matching placebo tablets were employed similarly . RESULTS In the intention-to-treat analysis , male sex , previous cardiovascular complications , older age , higher systolic BP , and smoking at r and omization were positively and independently correlated with cardiovascular risk . Furthermore , for total ( P = .009 ) and cardiovascular ( P = .09 ) mortality , the benefit of antihypertensive drug treatment weakened with advancing age ; for total mortality ( P = .05 ) , the benefit increased with higher systolic BP at entry , while for fatal and nonfatal stroke ( P = .01 ) , it was most evident in nonsmokers ( 92.5 % of all patients ) . In the per protocol analysis , active treatment reduced total mortality by 24 % ( P = .05 ) , reduced all fatal and nonfatal cardiovascular end points by 32 % ( P<.001 ) , reduced all strokes by 44 % ( P = .004 ) , reduced nonfatal strokes by 48 % ( P = .005 ) , and reduced all cardiac end points , including sudden death , by 26 % ( P = .05 ) . CONCLUSIONS In elderly patients with isolated systolic hypertension , stepwise antihypertensive drug treatment , starting with the dihydropyridine calcium channel blocker nitrendipine , improves prognosis . The per- protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths , 54 major cardiovascular end points , 29 strokes , or 25 cardiac end points . The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients Rationale Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale , oral anticoagulants and antiplatelet therapy in patients with patent foramen ovale-associated cryptogenic stroke Aim To assess whether transcatheter patent foramen ovale closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy , for secondary stroke prevention in patients aged 16 to 60 years with a large patent foramen ovale or a patent foramen ovale associated with an atrial septal aneurysm , and an otherwise unexplained ischaemic stroke or retinal ischaemia . Sample size Six hundred and sixty-four patients were included in the study . Methods and design CLOSE is an academic-driven , multicentre , r and omized , open-label , three-group , superiority trial with blinded adjudication of outcome events . The trial has been registered with Clinical Trials Register ( Clinical trials.gov , NCT00562289 ) . Patient recruitment started in December 2007 . Patient follow-up will continue until December 2016 . Expected mean follow-up = 5.6 years . Study outcomes The primary efficacy outcome is the occurrence of fatal or nonfatal stroke . Safety outcomes include fatal , life-threatening or major procedure- or device-related complications and fatal , life-threatening or major haemorrhagic complications . Discussion CLOSE is the first specifically design ed trial to assess the superiority of patent foramen ovale closure over antiplatelet therapy alone and the superiority of oral anticoagulants over antiplatelet therapy to prevent stroke recurrence in patients with patent foramen ovale-associated cryptogenic stroke BACKGROUND Dual antiplatelet therapy with aspirin and thienopyridines ( clopidogrel or prasugrel ) is required after placement of coronary stents to prevent thrombotic complications . Although current clinical practice guidelines recommend 12-month treatment after drug-eluting stent placement , even longer duration s may prevent thrombotic events . STUDY DESIGN The Dual Antiplatelet Therapy ( DAPT ) Study is comparing the benefits and risks of 12 versus 30 months of dual antiplatelet therapy in preventing stent thrombosis or major adverse cardiovascular and cerebrovascular events in subjects undergoing percutaneous coronary intervention ( PCI ) for the treatment of coronary artery obstructive lesions . The DAPT Study is a multicenter , international , r and omized , double-blind , placebo-controlled trial that will enroll 15,245 subjects treated with drug-eluting stent ( DES ) and 5,400 subjects treated with bare-metal stents ( BMS ) .  All subjects will receive 12 months of open-label thienopyridine treatment in addition to aspirin . After 12 months , subjects who are free from death , myocardial infa rct ion , or stroke ( MACCE ) , repeat revascularization , and GUSTO ( Global Use of Strategies to Open Occluded Coronary Arteries ) moderate or severe bleeding events will be r and omized to receive either 18 additional months of thienopyridine ( clopidogrel or prasugrel ) ( 30 month DAPT arm ) or placebo ( 12 month DAPT arm ) plus aspirin . Co primary end points are MACCE and stent thrombosis . The primary safety end point is GUSTO moderate or severe bleeding . CONCLUSIONS This r and omized trial is design ed to define the relative safety and effectiveness of 12 versus 30 months of dual antiplatelet therapy across the broad spectrum of patients receiving coronary stents Although many patients with long-term oral anticoagulation ( OAC )  can manage their medication safely and reliably themselves , no study on elderly patients has as yet assessed the safety and efficacy of OAC self-management  with major thromboembolic and haemorrhagic complications as primary outcomes . In this multi-centre trial , patients aged 60 years or more were r and omised into a  self-management ( SMG ) ( N = 99 ) or routine care group  ( RCG ) ( N = 96 ) . The primary outcome was the combined endpoint of all thromboembolic events requiring hospitalisation and all major bleeding complications . Mean follow-up was 2.9 + /- 1.2 and 3.0 + /- 1.1 years in the SMG and RCG , respectively . In intention-to-treat analysis , 12 patients in the SMG versus 22 patients in the RCG reached a primary endpoint ( hazard ratio [ HR ] : 0.50 ; 95 % confidence interval [ CI ] : 0.25 to 1.00 ; p = 0.049 ) . The post-hoc analysis on OAC treatment sensitivity supported the benefit of self-management ( HR 0.27 ; 95 % CI : 0.13 to 0.71 ; p = 0.006 ) . Fifteen patients in the SMG died during the study , but none of the deaths was directly associated with anticoagulation therapy . In the RCG , 11 patients died ; of those , three deaths were directly associated with anticoagulation therapy and there was one death of unknown cause . During follow-up , the quality of OAC control was significantly better in the SMG than in the RCG . In elderly patients , long-term self-management of oral anticoagulation is superior for the prevention of major thromboembolic and bleeding complications and for the quality of oral anticoagulation control compared to routine care for a mean follow-up period of three years
Acetylsalicylic acid ( ASA ) did not reduce stroke or ‘ all cardiovascular events ’ compared to placebo in primary prevention patients with elevated BP and no prior cardiovascular disease .
To conclude for primary prevention in patients with elevated BP , antiplatelet therapy with ASA can not be recommended since the magnitude of benefit , a reduction in myocardial infa rct ion , is negated by a harm of similar magnitude , an increase in major haemorrhage .
Although elevated systemic blood pressure ( BP ) results in high intravascular pressure , the main complications of hypertension are related to thrombosis rather than haemorrhage .
It therefore seemed plausible that use of antithrombotic therapy may be useful in preventing thrombosis-related complications of elevated BP .
The objectives were to conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with BP , to address the following hypotheses : ( i ) antiplatelet agents reduce total deaths and /or major thrombotic events when compared to placebo or other active treatment ; and ( ii ) oral anticoagulants reduce total deaths and /or major thromboembolic events when compared to placebo or other active treatment .