Prolonged vs Short Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With or Without Peripheral Arterial Disease: A Subgroup Analysis of the PRODIGY Randomized Clinical Trial. Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes 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. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study Clinical Relevance of Anticoagulation and Dual Antiplatelet Therapy to the Outcomes of Patients With Atrial Fibrillation and Recent Percutaneous Coronary Intervention With Stent 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  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. Bleeding Complications With Dual Antiplatelet Therapy Among Patients With Stable Vascular Disease or Risk Factors for Vascular Disease: Results From the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) Trial Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. Impact of clinical presentation on ischaemic and bleeding outcomes in patients receiving 6- or 24-month duration of dual-antiplatelet therapy after stent implantation: a pre-specified analysis from the PRODIGY (Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia) t Protocol for Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com): a randomized, open-label, parallel-group trial Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial. Effects of Triple Therapy in Patients With Non-Valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention Regarding Thromboembolic Risk Stratification. Ischemic and bleeding events in patients with myocardial infarction undergoing percutaneous coronary intervention who require oral anticoagulation: Insights from the Canadian observational AntiPlatelet sTudy. Impact of dual antiplatelet therapy on outcomes among aspirin-resistant patients following coronary artery bypass grafting. Pre-procedural dual antiplatelet therapy and bleeding events following transcatheter aortic valve implantation (TAVI). Characterising and predicting bleeding in high-risk patients with an acute coronary syndrome Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention.
Importance Patients with concomitant peripheral arterial disease ( PAD ) experience worse cardiovascular outcomes after percutaneous coronary intervention ( PCI ) . Objective To assess the efficacy and safety of prolonged ( 24 months ) vs short ( ≤6 months ) dual antiplatelet therapy ( DAPT ) in patients with PAD undergoing PCI . Design , Setting , and Participants This sub analysis of the r and omized Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study ( PRODIGY ) trial assessed unselected patients from tertiary care hospitals with stable coronary artery disease or acute coronary syndromes with or without concomitant PAD from December 2006 to December 2008 . Data analysis was performed from January 7 to April 4 , 2016 . Interventions Percutaneous coronary intervention . Main Outcomes and Measures Rates of the primary efficacy end point , composite of death , myocardial infa rct ion , or cerebrovascular accidents , and occurrence of the key safety end point , a composite of Bleeding Academic Research Consortium type 2 , 3 , or 5 . Results This analysis comprised 246 and 1724 patients with and without PAD , respectively . In the patients with PAD , mean ( SD ) age was 73.2 ( 9.2 ) in the prolonged group and 75.7 ( 8.7 ) years in the short DAPT group , and 97 ( 82.2 % ) were male in the prolonged group and 92 ( 71.9 % ) were male in the short DAPT group . In the patients without PAD , mean ( SD ) age was 67.1 ( 11.2 ) years in the prolonged group and 66.8 ( 11.3 ) years in the short DAPT group , and 667 ( 76.8 % ) were male in the prolonged group and 655 ( 76.6 % ) were male in the short DAPT group . Status of PAD was associated with a higher risk of death and ischemic events ( hazard ratio [ HR ] , 2.80 ; 95 % CI , 2.05 - 3.83 ; P < .001 ) . Prolonged vs short DAPT conveyed a lower risk of the primary efficacy end point in patients with PAD ( 19 [ 16.1 % ] vs 35 [ 27.3 % ] ; HR , 0.54 ; 95 % CI , 0.31 - 0.95 ; P = .03 ) but not in patients without PAD ( 81 [ 9.3 % ] vs 63 [ 7.4 % ] ; HR , 1.28 ; 95 % CI , 0.92 - 1.77 ; P = .15 ) , with positive interaction ( P = .01 ) . The risk of definite or probable stent thrombosis was significantly lower in patients with PAD treated with prolonged compared with short DAPT ( HR , 0.07 ; 95 % CI , 0 - 1.21 ; P = .01 ) . Bleeding Academic Research Consortium type 2 , 3 , or 5 bleeding occurred in 6 patients with PAD ( 5.2 % ) receiving prolonged DAPT relative to 8 ( 6.9 % ) of those receiving short DAPT ( HR , 0.77 ; 95 % CI , 0.27 - 2.21 ; P = .62 ) , with a significant interaction ( P = .04 ) compared with patients without PAD . Conclusions and Relevance Peripheral artery disease confers a poor prognosis in patients undergoing PCI in the setting of stable coronary artery disease or acute coronary syndromes . Prolonged DAPT lowers the risk of ischemic events with no apparent bleeding liability in this high-risk group . Trial Registration clinical trials.gov Identifier : NCT00611286 Objectives Dual antiplatelet therapy ( DAPT ) with aspirin + a P2Y12 inhibitor is recommended for at least 12 months for patients with acute coronary syndrome ( ACS ) , with shorter duration s considered for patients with increased bleeding risk . However , there are no decision support tools available to predict an individual patient ’s bleeding risk during DAPT treatment in the post-ACS setting . Methods To develop a longitudinal bleeding risk prediction model , we analy sed 9240 patients with unstable angina/non-ST segment elevation myocardial infa rct ion ( NSTEMI ) from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes ( TRILOGY ACS ) trial , who were managed without revasculari sation and treated with DAPT for a median of 14.8 months . Results We identified 10 significant baseline predictors of non-coronary artery bypass grafting (CABG)-related Global Use of Strategies to Open Occluded Arteries ( GUSTO ) severe/life-threatening/moderate bleeding : age , sex , weight , NSTEMI ( vs unstable angina ) , angiography performed before r and omi sation , prior peptic ulcer disease , creatinine , systolic blood pressure , haemoglobin and treatment with beta-blocker . The five significant baseline predictors of Thrombolysis In Myocardial Infa rct ion ( TIMI ) major or minor bleeding included age , sex , angiography performed before r and omi sation , creatinine and haemoglobin . The models showed good predictive accuracy with Therneau ’s C-indices : 0.78 ( SE = 0.024 ) for the GUSTO model and 0.67 ( SE = 0.023 ) for the TIMI model . Internal validation with bootstrapping gave similar C-indices of 0.77 and 0.65 , respectively . External validation demonstrated an attenuated C-index for the GUSTO model ( 0.69 ) but not the TIMI model ( 0.68 ) . Conclusions Longitudinal bleeding risks during treatment with DAPT in patients with ACS can be reliably predicted using selected baseline characteristics . The TRILOGY ACS bleeding models can inform risk –benefit considerations regarding the duration of DAPT following ACS . Trial registration Clinical Trials.gov identifier : https:// clinical 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 Aims Newer P2Y12 blockers ( prasugrel and ticagrelor ) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome ( ACS ) . However , both drugs are associated with an increase in bleeding complications . The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy ( DAPT ) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS . Methods and results We performed an open-label , monocentric , and r and omized trial . From March 2014 to April 2016 , patients admitted with ACS requiring coronary intervention , on aspirin and a newer P2Y12 blocker and without adverse event at 1 month , were assigned to switch to aspirin and clopidogrel ( switched DAPT ) or continuation of their drug regimen ( unchanged DAPT ) . The primary outcome was a composite of cardiovascular death , urgent revascularization , stroke and bleeding as defined by the Bleeding Academic Research Consortium ( BARC ) classification ≥2 at 1 year post ACS . Six hundred and forty six patients were r and omized and 645 analysed , corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group . The primary endpoint occurred in 43 ( 13.4 % ) patients in the switched DAPT group and in 85 ( 26.3 % ) patients in the unchanged DAPT ( HR 95%CI 0.48 ( 0.34 - 0.68 ) , P < 0.01 ) . No significant differences were reported on ischaemic endpoints , while BARC ≥ 2 bleeding occurred in 13 ( 4.0 % ) patients in the switched DAPT and in 48 ( 14.9 % ) in the unchanged DAPT group ( HR 95%CI 0.30 ( 0.18 - 0.50 ) , P < 0.01 ) . Conclusion A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS Background Chronic atrial fibrillation ( AF ) , coexisting with a history of recent coronary angioplasty with stent ( PCI-S ) , represents an encoded indication for oral anticoagulation ( OAC ) with warfarin plus dual antiplatelet therapy ( DAPT ) . Methods Using a retrospective cohort study , we determined the respective impacts on cardiovascular outcomes of three different pharmacologic regimens , i.e. , triple therapy ( TT ) with warfarin + clopidogrel and aspirin , dual therapy ( DT ) with warfarin + clopidogrel or aspirin , and DAPT with clopidogrel + aspirin . Outcomes of interest were all-cause mortality , ischemic cardiac events , ischemic cerebral events , and bleeding events . The inclusion criterion was the coexistence of an indication for OAC ( e.g. , chronic AF ) with an indication for DAPT due to recent PCI-S. Results Among the 98 patients enrolled , 48 ( 49 % ) , 31 ( 31.6 % ) , and 19 ( 19.4 % ) patients were prescribed TT , DT , and DAPT , respectively . Throughout a mean follow-up of 378 ± 15.7 days , there were no significant differences between the three regimens for all abovementioned outcomes . In particular , the total frequency of major bleeding was similar in the three groups : five cases ( 10.4 % ) in TT , one case ( 3.22 % ) in DT and no case in DAPT groups ( Chi-square test , P = 0.1987 ) . Conclusions TT , DT and DAPT displayed similar efficacy and safety . Although the superiority of OAC vs. DAPT for stroke prevention in AF patients has been demonstrated by previous r and omized trials , a smaller frequency of high thromboembolic risks ’ features in DAPT group of the present study may have prevented the observation of a higher incidence of ischemic stroke in this group 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 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 Background — Uncertainty exists about the frequency , correlates , and clinical significance of bleeding with dual antiplatelet therapy ( DAPT ) , particularly over an extended period in a stable population . We sought to determine the frequency and time course of bleeding with DAPT in patients with established vascular disease or risk factors only ; identify correlates of bleeding ; and determine whether bleeding is associated with mortality . Methods and Results — We analyzed 15 603 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management , and Avoidance ( CHARISMA ) trial , a double-blind , placebo-controlled , r and omized trial comparing long-term clopidogrel 75 mg/d versus placebo ;  all patients received aspirin ( 75 to 162 mg ) daily . Patients had either established stable vascular disease or multiple risk factors for vascular disease without established disease . Median follow-up was 28 months . Bleeding was assessed with the use of the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries ( GUSTO ) criteria . Severe bleeding occurred in 1.7 % of the clopidogrel group versus 1.3 % on placebo ( P=0.087 ) ; moderate bleeding occurred in 2.1 % versus 1.3 % , respectively ( P<0.001 ) . The risk of bleeding was greatest the first year . Patients without moderate or severe bleeding during the first year were no more likely than placebo-treated patients to have bleeding thereafter . The frequency of bleeding was similar in patients with established disease and risk factors only . In multivariable analysis , the relationship between moderate bleeding and all-cause mortality was strong ( hazard ratio , 2.55 ; 95 % confidence interval , 1.71 to 3.80 ; P<0.0001 ) , along with myocardial infa rct ion ( hazard ratio , 2.92 ; 95 % confidence interval , 2.04 to 4.18 ; P<0.0001 ) and stroke ( hazard ratio , 4.20 ; 95 % confidence interval , 3.05 to 5.77 ; P<0.0001 ) . Conclusions — In CHARISMA , there was an increased risk of bleeding with long-term clopidogrel . The incremental risk of bleeding was greatest in the first year and similar thereafter . Moderate bleeding was strongly associated with mortality . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00050817 Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a key strategy to reduce platelet reactivity and to prevent thrombotic events in patients treated with percutaneous coronary intervention . In an earlier consensus document , we proposed cutoff values for high on-treatment platelet reactivity to adenosine diphosphate ( ADP ) associated with post-percutaneous coronary intervention ischemic events for various platelet function tests ( PFTs ) . Up date d American and European practice guidelines have issued a Class IIb recommendation for PFT to facilitate the choice of P2Y12 receptor inhibitor in selected high-risk patients treated with percutaneous coronary intervention , although routine testing is not recommended ( Class III ) . Accumulated data from large studies underscore the importance of high on-treatment platelet reactivity to ADP as a prognostic risk factor . Recent prospect i ve r and omized trials of PFT did not demonstrate clinical benefit , thus question ing whether treatment modification based on the results of current PFT platforms can actually influence outcomes . However , there are major limitations associated with these r and omized trials . In addition , recent data suggest that low on-treatment platelet reactivity to ADP is associated with a higher risk of bleeding . Therefore , a therapeutic window concept has been proposed for P2Y12 inhibitor therapy . In this up date d consensus document , we review the available evidence addressing the relation of platelet reactivity to thrombotic and bleeding events . In addition , we propose cutoff values for high and low on-treatment platelet reactivity to ADP that might be used in future investigations of personalized antiplatelet therapy AIMS We investigated if acute coronary syndrome ( ACS ) rather than stable coronary artery disease ( SCAD ) presentation is an outcome modifier with respect to the duration of dual-antiplatelet therapy ( DAPT ) in patients undergoing coronary stenting .  METHODS AND RESULTS In the Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia ( PRODIGY ) trial , a total of 1465 ( 74.3 % ) patients presented ACS whereas 505 ( 25.7 % ) had SCAD and were r and omized to 6- or 24-month DAPT . At 24 months , the composite of death , myocardial infa rct ion ( MI ) , or cerebrovascular accident ( CVA ) did not differ between the long- and short-term DAPT arms in both ACS ( 11.1 vs. 11.7 % ; P = 0.67 ) and SCAD ( 7.5 vs. 4.8 % ; P = 0.21 ) patients , respectively . Long-term DAPT was associated with a 75 % increase of Bleeding Academic Research Consortium (BARC)-class 2 , 3 , or 5 bleeding in ACS [ 7.1 vs. 4.1 % ; hazard ratio ( HR ) 1.75 , 95 % confidence interval ( CI ) 1.11 - 2.74 , P = 0.015 ; number needed to treat for harm ( NNTH ) : 33.3 ] and a five-fold increase in SCAD ( 8.2 vs. 1.6 % ; HR 5.37 , 95 % CI 1.84 - 15.74 , P = 0.002 ; NNTH : 15.1 ) patients , with a borderline quantitative interaction ( PINT = 0.056 ) . As a result , net adverse cardiovascular events ( death , MI , CVA , BARC class 2 , 3 , or 5 bleeding ) were more than doubled in SCAD patients receiving 24-month DAPT , whereas they did not differ in ACS patients ( PINT = 0.024 ) . CONCLUSIONS This analysis suggests that clinical presentation may be a treatment modifier with respect to DAPT duration after stenting consistent with the hypothesis that SCAD-but not ACS- patients are exposed to a significant increase in bleeding and net adverse clinical events when treated with 24-month compared with 6-month therapy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00611286 . http:// clinical trials.gov/ct2/show/NCT00611286?term=prodigy&rank=2 Rationale and aims Monotherapy with antiplatelet agents is only modestly effective in secondary prevention of ischemic stroke ( IS ) , particularly in patients with multiple risk factors such as cervicocephalic arterial stenosis , diabetes , and hypertension . While dual antiplatelet therapy ( DAPT ) with aspirin and clopidogrel reduced IS recurrence , particularly in the early stages after IS , it increased the risk of bleeding . Compared with aspirin , cilostazol prevented IS recurrence without increasing the incidence of serious bleeds . In patients with intracranial arterial stenosis , no significant increase in bleeding events was observed for DAPT with cilostazol and aspirin , compared to that for aspirin monotherapy . DAPT involving cilostazol may therefore be safer than conventional DAPT . These findings prompted us to conduct the Cilostazol Stroke Prevention Study for Antiplatelet Combination ( CSPS.com ; Clinical Trials.gov identifier : NCT01995370 ) to evaluate the safety and efficacy of DAPT involving cilostazol for secondary IS prevention , in comparison with that of antiplatelet monotherapy . Design The CSPS.com is a multicenter , r and omized , open-label , parallel-group trial . A total of 4000 high-risk patients with noncardioembolic IS will be r and omized 8–180 days after onset to receive aspirin or clopidogrel monotherapy , or DAPT with cilostazol and aspirin or clopidogrel for at least one-year . Study outcomes The primary outcome is IS recurrence . Secondary outcomes are composite occurrences of any stroke , death from any cause , myocardial infa rct ion , vascular death , and other vascular events . Discussion The CSPS.com is expected to provide evidence indicating whether secondary IS prevention in high-risk patients can be improved by using DAPT involving cilostazol AIMS The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention  , with a uniform use of Biolimus A9-eluting stents ( BES ) and bivalirudin .  GLOBAL LEADERS was design ed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid ( ASA ) , compared to conventional dual antiplatelet therapy ( DAPT ) , improves outcomes . METHODS AND RESULTS Patients ( n > 16,000 ) are r and omised ( 1:1 ratio ) to ticagrelor  90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor ( acute coronary syndrome ) or clopidogrel ( stable coronary artery disease ) for 12 months plus ASA ≤100 mg for 24 months . The primary outcome is a composite of all-cause mortality or non-fatal , new Q-wave myocardial infa rct ion at 24 months . The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium ( BARC ) definitions . Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates . CONCLUSIONS The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events , across a wide spectrum of patients , following BES implantation BACKGROUND The effects of dual antiplatelet therapy ( DAPT ) and triple therapy ( TT : DAPT plus oral anticoagulation ) in patients with atrial fibrillation ( AF ) undergoing percutaneous coronary intervention ( PCI ) regarding to CHA2DS2-VASc score remain undefined . We compare the effect of TT vs. DAPT in this setting regarding the CHA2DS2-VASc score . METHODS AND RESULTS In a prospect i ve multicenter registry , 585 patients ( 75.2 % male , 73.2 ± 8.2 years ) with AF undergoing PCI were followed up during 1 year . Of them , 157 ( 26.8 % ) had a CHA2DS2-VASc=1 , and 428 ( 73.2 % ) had a CHA2DS2-VASc ≥2 . TT was prescribed in 51.6 % with CHA2DS2-VASc=1 and in 55.5 % with CHA2DS2-VASc ≥ 2 . Patients with CHA2DS2-VASc=1 receiving TT had a similar thromboembolism rate to those on DAPT ( 1.2 % vs. 1.3 % , P=0.73 ) , but more total ( 19.5 % vs. 6.9 % , P=0.01 ) and a tendency to more major ( 4.9 % vs. 0 % , P=0.06 ) bleeding . However , patients with CHA2DS2-VASc ≥ 2 receiving TT had a lower thromboembolism rate ( 1.7 % vs. 5.3 % , P=0.03 ) and a trend towards more bleeds ( 21.8 % vs. 15.6 % , P=0.06 ) , with an excess of major bleeding ( 8.4 % vs. 3.1 % , P=0.01 ) . Rates of major adverse cardiac events ( MACE ) in both CHA2DS2-VASc subgroups were similar , irrespective of treatment . In a Cox multivariate analysis , TT was associated to major bleeding , but not with MACE . CONCLUSIONS In patients with AF and CHA2DS2-VASc=1 undergoing PCI , the use of TT involves a high risk of bleeding without a significant benefit in preventing thromboembolism BACKGROUND Since the introduction of newer , more potent P2Y12 receptor inhibitors ( P2Y12ris ) , practice patterns and associated clinical outcomes in patients with myocardial infa rct ion ( MI ) undergoing percutaneous coronary intervention ( PCI ) and also requiring oral anticoagulation ( OAC )  have not been fully characterized . METHODS The Canadian Observational Antiplatelet Study was a prospect i ve , multicenter , longitudinal , observational study ( 26 hospitals , December 2011 to May 2013 ) describing P2Y12ri treatment patterns and outcomes in patients with ST-elevation and non-ST-elevation MI undergoing PCI . We describe the clinical characteristics , treatment patterns , bleeding , and ischemic outcomes over the 15-month follow-up within and between the subgroups of patients discharged on either dual-antiplatelet therapy ( DAPT ) ( acetyl salicylic acid [ASA]+P2Y12ri ) or triple therapy ( ASA+P2Y12ri+OAC ) . RESULTS Of the 2,034 patients at discharge , 86 % ( n = 1,757 ) were on DAPT , whereas 14 % ( n = 277 ) were on triple therapy ( 50 % warfarin , 50 % non-vitamin K OAC [ NOAC ] ) . The frequency of newer P2Y12ri use ( prasugrel or ticagrelor ) was similar in the DAPT and triple therapy groups ( 28 % vs 26 % , respectively ) . In the triple therapy group , NOAC use was higher in those receiving a new P2Y12ri compared to those receiving clopidogrel ( 75 % vs 41 % , respectively , P < .0001 ) . The unadjusted and adjusted events of major cardiovascular event ( MACE ) and bleeding were higher in the triple therapy group . For patients on triple therapy , the bleeding or MACE events were not significantly different between those on clopidogrel versus those on ticagrelor or prasugrel . CONCLUSION In this observational study of MI patients requiring PCI , 1 in 8 were discharged on triple antithrombotic therapy , of whom 26 % were on newer P2Y12ris . Patients on triple therapy had higher risk at baseline , with higher unadjusted and adjusted MACE and bleeding events compared to those on DAPT alone . Among triple therapy-treated patients , there was no difference in the MACE and bleeding events regardless of the P2Y12ri used Coronary artery bypass grafting is pivotal in the contemporary management of complex coronary artery disease . Interpatient variability to antiplatelet agents , however , harbors the potential to compromise the revascularization benefit by increasing the incidence of adverse events . This study was design ed to define the impact of dual antiplatelet therapy ( dAPT ) on clinical outcomes among aspirin-resistant patients who underwent coronary artery surgery .  We r and omly assigned 219 aspirin-resistant patients according to multiple electrode aggregometry to receive clopidogrel ( 75 mg ) plus aspirin ( 300 mg ) or aspirin-monotherapy ( 300 mg ) . The primary end point was a composite outcome of all-cause death , nonfatal myocardial infa rct ion , stroke , or cardiovascular hospitalization assessed at 6 months postoperatively . The primary end point occurred in 6 % of patients assigned to dAPT and 10 % of patients r and omized to aspirin-monotherapy ( relative risk 0.61 , 95 % confidence interval 0.25 to 1.51 , p = 0.33 ) . No significant treatment effect was noted in the occurrence of the safety end point . The total incidence of bleeding events was 25 % and 19 % in the dAPT and aspirin-monotherapy groups , respectively ( relative risk 1.34 , 95 % confidence interval 0.80 to 2.23 , p = 0.33 ) . In the subgroup analysis , dAPT led to lower rates of adverse events in patients with a body mass index > 30 kg/m(2 ) ( 0 % vs 18 % , p < 0.01 ) and those < 65 years ( 0 % vs 10 % , p = 0.02 ) . In conclusion , the addition of clopidogrel in patients found to be aspirin resistant after coronary artery bypass grafting did not reduce the incidence of adverse events , nor did it increase the number of recorded bleeding events . dAPT did , however , lower the incidence of the primary end point in obese patients and those < 65 years INTRODUCTION Transcatheter aortic valve implantation ( TAVI )  is associated with bleeding that increases mortality . Dual antiplatelet therapy ( DAPT ) is recommended in TAVI , however little is known about pre-procedural DAPT use and its impact on hemostasis . We sought to determine the frequency , predictors and bleeding events in patients receiving DAPT before TAVI . METHODS Three-hundred- and -three ( n=303 , 78.6±7.6years , 49 % female , EuroScore 23.1±16.9 ) consecutive patients undergoing TAVI  were prospect ively analyzed and followed for in-hospital events . According to pre-procedural antiplatelet status study population was divided into 2 groups : patients receiving aspirin and clopidogrel ( DAPT ) and those on aspirin only or no antiplatelet therapy ( noDAPT ) . RESULTS Pre-procedural DAPT was used in 139 cases ( 46 % ) . Previous PCI ( OR 4.8 , [ 2.8 - 8.3 ] , p<0.0001 ) , implantation of self-exp and able prosthesis ( OR 2.2 , [ 1.2 - 4 ] , p=0.007 ) femoral access ( OR 2.2 , [ 1.1 - 4.5 ] , p=0.029 ) and platelet count ( OR 1.006 , [ 1.002 - 1.01 ] , p=0.002 ) were identified as independent predictors of pre-procedural DAPT . No difference was observed in the rates of any bleeding ( 23 % in DAPT vs. 24.4 % in noDAPT , p=0.930 ) or major/life-threatening bleeding ( 12.2 % in DAPT vs. 14.7 % in noDAPT , p=0.715 ) . Propensity-score matching analysis did not alter the results . GFR < 30ml/min was the strongest predictor of bleeding ( OR 4.3 , [ 1.9 - 9.9 ] , p=0.0005 ) . There was a trend towards lower frequency of MI and stroke/TIA in DAPT as compared with noDAPT ( 3.6 % vs. 9.8 % , p=0.082 ) . CONCLUSIONS Pre-procedural DAPT is frequent and does not increase short-term bleeding complications or need for transfusion  following TAVI . Possible impact of DAPT use before TAVI on ischemic complications needs to be investigated in larger population Objective In the Apixaban for Prevention of Acute Ischemic Events ( APPRAISE-2 ) trial , the use of apixaban , when compared with placebo , in high-risk patients with a recent acute coronary syndrome ( ACS ) result ed in a significant increase in bleeding without a reduction in ischaemic events . The aim of this analysis was to provide further description of these bleeding events and to determine the baseline characteristics associated with bleeding in high-risk post-ACS patients . Methods APPRAISE-2 was a multinational clinical trial including 7392 high-risk patients with a recent ACS r and omised to apixaban ( 5 mg twice daily ) or placebo .  Bleeding including Thrombolysis in Myocardial Infa rct ion ( TIMI ) major or minor bleeding , International Society on Thrombosis and Haemostasis ( ISTH ) major or clinical ly relevant non-major ( CRNM ) bleeding , and any bleeding were analysed using an on-treatment analysis . Kaplan – Meier curves were plotted to describe the timing of bleeding , and a Cox proportional hazards model was used to identify predictors of ISTH major or CRNM bleeding and any bleeding . Median follow-up was 241 days . Results The proportion of patients who experienced TIMI major or minor , ISTH major or CRNM , and any bleeding was 1.5 % , 2.2 % and 13.3 % , respectively . The incidence of bleeding was highest in the immediate post-ACS period ( 0.11 in the first 30 days vs 0.03 after 30 days events per 1 patient-year ) ; however , > 60 % of major bleeding events occurred > 30 days after the end of the index hospitalisation . Gastrointestinal bleeding was the most common cause of major bleeding , accounting for 45.9 % of TIMI major or minor and 39.5 % of ISTH major or CRNM bleeding events . Independent predictors of ISTH major or CRNM bleeding events included older age , renal dysfunction , dual oral antiplatelet therapy , smoking history , increased white cell count and coronary revascularisation . Conclusions When compared with placebo , the use of apixaban is associated with an important short-term and long-term risk of bleeding in high-risk post-ACS patients , with gastrointestinal bleeding being the most common source of major bleeding . The baseline predictors of major bleeding appear to be consistent with those identified in lower-risk ACS population s with shorter-term follow-up . Clinical trial No NCT00831441 IMPORTANCE Dual antiplatelet therapy after percutaneous coronary intervention ( PCI ) reduces ischemia but increases bleeding . OBJECTIVE To develop a clinical decision tool to identify patients expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI . DESIGN , SETTING , AND PARTICIPANTS Among 11,648 r and omized DAPT Study patients from 11 countries ( August 2009-May 2014 ) , a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI . Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries r and omized in the PROTECT trial ( June 2007-July 2014 ) . EXPOSURES Twelve months of open-label thienopyridine plus aspirin , then r and omized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin . MAIN OUTCOMES AND MEASURES Ischemia ( myocardial infa rct ion or stent thrombosis ) and bleeding ( moderate or severe ) 12 to 30 months after PCI . RESULTS Among DAPT Study patients ( derivation cohort ; mean age , 61.3 years ; women , 25.1 % ) , ischemia occurred in 348 patients ( 3.0 % ) and bleeding in 215 ( 1.8 % ) . Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68 , respectively . The prediction rule assigned 1 point each for myocardial infa rct ion at presentation , prior myocardial infa rct ion or PCI , diabetes , stent diameter less than 3 mm , smoking , and paclitaxel-eluting stent ; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention ; -1 point for age 65 to younger than 75 years ; and -2 points for age 75 years or older . Among the high score group ( score ≥2 , n = 5917 ) , continued thienopyridine vs placebo was associated with reduced ischemic events ( 2.7 % vs 5.7 % ; risk difference [ RD ] , -3.0 % [ 95 % CI , -4.1 % to -2.0 % ] , P < .001 ) compared with the low score group ( score < 2 , n = 5731 ; 1.7 % vs 2.3 % ; RD , -0.7 % [ 95 % CI , -1.4 % to 0.09 % ] , P = .07 ; interaction P < .001 ) . Conversely , continued thienopyridine was associated with smaller increases in bleeding among the high score group ( 1.8 % vs 1.4 % ; RD , 0.4 % [ 95 % CI , -0.3 % to 1.0 % ] , P = .26 ) compared with the low score group ( 3.0 % vs 1.4 % ; RD , 1.5 % [ 95 % CI , 0.8 % to 2.3 % ] , P < .001 ; interaction P = .02 ) . Among PROTECT patients ( validation cohort ; mean age , 62 years ; women , 23.7 % ) , ischemia occurred in 79 patients ( 1.0 % ) and bleeding in 37 ( 0.5 % ) , with a c statistic of 0.64 for ischemia and 0.64 for bleeding . In this cohort , the high-score patients ( n = 2848 ) had increased ischemic events compared with the low-score patients and no significant difference in bleeding . CONCLUSION AND RELEVANCE Among patients not sustaining major bleeding or ischemic events 1 year after PCI , a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts . This rule requires further prospect i ve evaluation to assess potential effects on patient care , as well as validation in other cohorts . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00977938
Most studies indicated that low on-treatment platelet reactivity ( LTPR ) , as measured by several platelet function tests , and the carriage of CYP2C19 * 17 allele were independent risk factors for bleeding .
A bleeding score also proved to be helpful in identifying patients at risk .
Several patient characteristics were also identified as independent predictors of bleeding , such as older age , female sex and renal failure .
Patients with coronary artery disease are usually treated with dual antiplatelet therapy ( DAPT ) after percutaneous coronary intervention .
Patients on DAPT are at risk of both ischaemic and bleeding events .
Although side-lined for a long time , real-life studies have shown that both the incidence and the associated morbidity and mortality of out-of-hospital bleeding are high .
This indicates that prevention of ( post-interventional ) bleeding is as important as prevention of ischaemia .
For this purpose it is crucial to reliably identify patients with a high bleeding risk .
In order to postulate an algorithm , which could help identifying these patients , we performed a systematic review to determine the value of previously proposed prognostic modalities for bleeding .