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  Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes 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 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 Clinical Relevance of Anticoagulation and Dual Antiplatelet Therapy to the Outcomes of Patients With Atrial Fibrillation and Recent Percutaneous Coronary Intervention With Stent 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 Thrombelastographic hypercoagulability and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): a randomized controlled trial 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. 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. Impact of dual antiplatelet therapy on outcomes among aspirin-resistant patients following coronary artery bypass grafting. Protocol for Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com): a randomized, open-label, parallel-group trial Dual Antiplatelet Therapy and Outcomes in Patients With Atrial Fibrillation and Acute Coronary Syndromes Managed Medically Without Revascularization: Insights From the TRILOGY ACS Trial 6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: the randomized, multicenter ITALIC trial. Long-term versus short-term dual antiplatelet therapy was similarly associated with a lower risk of death, stroke, or infarction in patients with acute coronary syndrome regardless of underlying kidney disease. High On-Treatment Platelet Reactivity as a Risk Factor for Secondary Prevention After Coronary Stent Revascularization: A Landmark Analysis of the ARCTIC Study Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery
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 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 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 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 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 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 — 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 Abstract A hypercoagulable state has , in observational studies , been associated with increased risk of thromboembolic events . The aim of this trial was to study whether dual antiplatelet therapy ( DAPT ) with clopidogrel in addition to aspirin could reduce the rate of graft occlusions , thromboembolic events , and death compared to aspirin monotherapy in hypercoagulable patients undergoing coronary artery bypass surgery . A total of 1683 patients were screened for eligibility , among which 165 patients were r and omized and 133 patients underwent multislice computed tomography scan to evaluate their grafts .  Thrombelastography ( TEG ) and multiplate aggregometry  were performed before and after surgery , and again at three months follow up . TEG hypercoagulability was defined as the maximum amplitude above 69 mm . At three months follow up , 17 out of 66 ( 25.7 % ) DAPT patients and 15 of 67 ( 22.4 % ) aspirin patients had significant graft stenosis or occlusions ( p = 0.839 ) . Saphenous vein grafts ( SVGs ) were stenosed or occluded in 15 ( 22.7 % ) patients in the DAPT group and 7 ( 10.4 % ) in the aspirin group ( p = 0.167 ) . Thromboembolic events and death after the second postoperative day ( when clopidogrel was started ) were numerically , but not statistically , lower in the DAPT group , 3 ( 3.8 % ) vs. 8 ( 9.9 % ) , p = 0.211 . In univariate logistic regression analysis , only postoperative day 4 platelet response to aspirin measured with multiplate was correlated with graft occlusion , OR 1.020 [ 1.002–1.039 ] , p = 0.033 . This is the first trial to test the hypothesis of intensified antiplatelet therapy in hypercoagulable patients . Due to the low enrollment and high loss to follow up , our results can only be viewed as hypothesis generating . We found a high rate of graft occlusions in this patient population . Our results were not suggestive of that DAPT improved saphenous vein graft patency . A trend was observed in patients on DAPT toward fewer MI and deaths . Postoperative response to aspirin therapy was found to be associated with early SVG occlusion 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 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 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 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 Associations between atrial fibrillation ( AF ) , outcomes , and response to  antiplatelet therapies  in patients with acute coronary syndrome ( ACS ) managed medically without revascularization remain uncertain . We examined these associations for medically managed ACS patients r and omized to dual antiplatelet therapy ( DAPT ) using patient data from the TRILOGY ACS trial . DAPT included aspirin plus clopidogrel 75 mg/d or prasugrel 10 mg/d ( 5 mg/d for those < 60 kg or age ≥75 years ) . Patients receiving oral anticoagulants were excluded . Cox proportional hazards regression modeling was used to characterize associations between patients with AF ( AF+ ) vs those without ( AF− ) and risk of ischemic and bleeding events , and to explore effects of r and omized treatment on outcomes . Among 9101 patients with baseline AF status , 710 ( 7.8 % ) had AF . AF+ patients were older and had more comorbidities . Unadjusted associations of the composite of cardiovascular death/myocardial infa rct ion/stroke were significantly higher among AF patients at 30 months ( 31.1 % vs 18.4 % ; HR : 1.61 , 95 % CI : 1.35‐1.92 , P < 0.001 ) , but differences did not persist after adjustment ( HR : 1.16 , 95 % CI : 0.97‐1.39 , P = 0.11 ) . When individual components of the composite endpoint were evaluated , 30‐month risk of events in AF+ patients was significantly higher . Thirty‐month risk of all‐cause death was significantly higher in AF+ patients : 18.1 % vs 11.1 % ( HR : 1.62 , 95 % CI : 1.30‐2.02 , P < 0.001 ) . There was no significant interaction with r and omized treatment and AF for the primary endpoint . Among medically managed high‐risk ACS patients receiving DAPT , AF was associated with higher unadjusted risks of ischemic and bleeding outcomes that were similar by treatment group BACKGROUND The currently recommended duration of dual antiplatelet therapy ( DAPT ) in drug-eluting stent ( DES ) recipients is 12 months to reduce the risk of late stent thrombosis , particularly in those with acute coronary syndrome ( ACS ) . OBJECTIVES This study hypothesized that antiplatelet treatment with DAPT for 6 months may be noninferior to 24-month DAPT in aspirin-sensitive patients . METHODS A multicenter , r and omized study assigned patients undergoing implantation of everolimus-eluting stents with confirmed nonresistance to aspirin to receive 6- or 24-month DAPT . The primary endpoint was a composite of death , myocardial infa rct ion , urgent target vessel revascularization , stroke , and major bleeding at 12 months post-stenting . RESULTS A total of 2,031 patients were enrolled in 70 European and Middle Eastern centers . The trial was prematurely terminated due to recruitment problems , leaving 941 patients r and omized to 24-month DAPT and 953 to 6-month DAPT . The 2 treatment groups had similar baseline and procedural characteristics . There was no significant difference in the primary endpoint ( 24-month : 1.5 % vs. 6-month : 1.6 % ; p = 0.85 ) . Noninferiority was demonstrated for 6- versus 24-month DAPT , with an absolute risk difference of 0.11 % ( 95 % confidence interval : -1.04 % to 1.26 % ; p for noninferiority = 0.0002 ) . There were no significant differences in stent thrombosis or bleeding complications . In the 792 ( 44 % ) high-risk patients with ACS , primary and secondary endpoints did not significantly differ ( hazard ratio : 1.7 [ 95 % confidence interval : 0.519 to 6.057 ; p = 0.361 ] ) . CONCLUSIONS Rates of bleeding and thrombotic events were not significantly different according to 6- versus 24-month DAPT after PCI with new-generation DES in good aspirin responders . ( Is There A LIfe for DES After Discontinuation of Clopidogrel [ ITALICplus ] ; NCT01476020 ) Scarce and conflicting evidence exists on whether clopidogrel is effective and whether dual antiplatelet treatment ( DAPT ) is safe in patients with acute coronary syndrome and chronic kidney disease ( CKD ) . To study this , we performed an observational , prospect i ve , multicenter cohort study of 36,001 patients of the SWEDEHEART registry . The exposure was DAPT prolonged after 3 months versus DAPT stopped at 3 months in consecutive patients with acute coronary syndrome and known serum creatinine .  DAPT duration with clopidogrel and aspirin was assessed by dispensed tablets . CKD stages were classified according to estimated glomerular filtration rate ( eGFR ) . Study outcomes were 1 ) the composite of death , myocardial infa rct ion , or ischemic stroke ; 2 ) bleeding ; or 3 ) the aggregate of these two outcomes within day 111 and 365 from discharge . A longer DAPT duration , as compared with 3-month DAPT , was associated with lower hazard ratios for outcome one in each CKD stratum ( eGFR over 60 , adjusted hazard ratio [ 95 % confidence interval ] 0.76 [ 0.67 - 0.85 ] ; eGFR 60 and less , 0.84 [ 0.73 - 0.96 ] , of which eGFR between 45 and 60 , 0.85 [ 0.70 - 1.05 ] , eGFR between 30 and 45 , 0.78 [ 0.62 - 0.97 ] ; eGFR 30 and less ml/min/1.73 m2 , 0.93 [ 0.70 - 1.24 ] . Bleeding ( outcome 2 ) was in general more common in the longer DAPT group of each aforementioned CKD stratum . Aggregated outcome analysis ( outcome 3 ) similarly favored longer DAPT in each stratum . There was no interaction between DAPT duration and CKD strata for any of the study outcomes . Thus , a prolonged as compared with three-month DAPT was similarly associated with a lower risk of death , stroke , or reinfa rct ion regardless of underlying CKD Background — Individualizing antiplatelet therapy after platelet function testing did not improve outcome after coronary stenting in the Assessment by a Double R and omization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting ( A RCT IC ) study . Whether results are different during the phase of secondary prevention starting after hospital discharge , when periprocedural events have been excluded , is unknown . Methods and Results — In A RCT IC , 2440 patients were r and omized before coronary stenting to a strategy of platelet function monitoring ( VerifyNow P2Y12/aspirin point-of-care assay ) with drug adjustment in suboptimal responders to antiplatelet therapy or to a conventional strategy without monitoring and without drug or dose changes . We performed a l and mark analysis starting at the time of hospital discharge evaluating the primary end point of death , myocardial infa rct ion , stent thrombosis , stroke , or urgent revascularization through 1 year . After discharge , the primary end point occurred in 8.6 % of patients in the monitoring arm and 7.9 % in the conventional arm ( hazard ratio , 1.105 ; 95 % confidence interval , 0.835–1.461 ; P=0.48 ) . Stent thrombosis or urgent revascularization occurred in 4.4 % and 4.5 % in the monitoring and conventional arms , respectively ( P=0.99 ) . There was no difference for any of the other ischemic end points . Major bleeding event rates were 1.8 % in the monitoring arm and 2.8 % in the conventional arm ( P=0.11 ) , whereas major or minor bleeding event rates were 2.3 % and 3.4 % , respectively ( P=0.10 ) . Conclusions — Detection of platelet hyper-reactivity by platelet function testing in patients undergoing coronary stenting with further therapeutic adjustment does not reduce ischemic recurrences after intervention . On-treatment platelet hyperreactivity can not be considered as a risk factor requiring intervention for secondary prevention after percutaneous coronary revascularization . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00827411 Coronary artery bypass grafting (CABG)-related bleeding complications and perioperative coronary events are strongly influenced by the management of antithrombotic therapy before and after CABG . Bleeding but also blood products transfusion increase the risk of death and compromise the long-term benefits of CABG.1 The use of new P2Y12 inhibitors , increasing pre-CABG percutaneous coronary interventions ( PCI ) with drug eluting stents ( DES ) requiring specific antiplatelet regimens , and advances in surgical technique has prompted the ESC Working Group on Cardiovascular Surgery and the ESC Working Group on Thrombosis to review the evidence of peri-CABG recommendations on antithrombotic management . Due to the paucity of r and omized trials , most of the evidence is still derived from observational studies and expert consensus , further reinforcing the importance of a multidisciplinary consultation for optimal decision making . # # # Benefits of preoperative aspirin Aspirin ( acetylsalicylic acid , ASA ) is recommended as secondary prevention therapy for all patients with proven coronary artery disease ( CAD ) and without contraindications . Its indication is even stronger for post-CABG patients ( recommendation IA).2 The general consensus is that ASA treatment withdrawal has ominous prognostic implication s in patients with CAD , especially in those with intracoronary stents , and should be advocated only when the bleeding risk clearly outweighs that of atherothrombotic events.3 The benefits of continuing ASA until the day of CABG ( ‘ preoperative ASA ’ ) are less clear and may explain the wide variability in the management of ASA therapy in the perioperative period and differences between guidelines endorsed by different professional and scientific societies ( Supplementary material online , Table S1 ) . This was based on the demonstration that ASA started the day before surgery was no more effective than ASA started 6 h after surgery at improving early ( 7- to 10-day ) graft patency , but was associated with increased bleeding complications.4 More recent evidence suggests , however , that ASA use within 5–7 days prior to CABG
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 .