***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 — Thrombin is a key mediator of platelet activation . Atopaxar is a reversible protease-activated receptor-1 antagonist that interferes with thrombin-mediated platelet effects . The phase II Lessons From Antagonizing the Cellular Effect of Thrombin – Coronary Artery Disease ( LANCELOT – CAD ) trial examined the safety and tolerability of prolonged therapy with atopaxar in subjects with CAD . Methods and Results — Subjects with a qualifying history were r and omized in a double-blind fashion to 3 dosing regimens of atopaxar ( 50 , 100 , or 200 mg daily ) or matching placebo for 24 weeks and followed up for an additional 4 weeks . The key safety end points were bleeding according to the Clopidogrel in Unstable Angina to Prevent Recurrent Events ( CURE ) and Thrombolysis in Myocardial Infa rct ion ( TIMI ) classifications . Secondary objectives included platelet aggregation and major adverse cardiac events .  Seven hundred and twenty subjects were r and omized .  Overall bleeding rates tended to be higher with atopaxar compared with placebo by CURE criteria ( placebo , 0.6 % ; atopaxar , 3.9 % ; relative risk , 6.82 , P=0.03 ; 50 mg , 3.9 % ; 100 mg , 1.7 % ; 200 mg , 5.9 % ; P for trend=0.01 ) and TIMI criteria ( placebo , 6.8 % ; atopaxar , 10.3 % ; relative risk , 1.52 , P=0.17 ; 50 mg , 9.9 % ; 100 mg , 8.1 % ; 200 mg , 12.9 % ; P for trend=0.07 ) . There was no difference in major bleeding . Major adverse cardiac events were numerically lower in the atopaxar subjects . All atopaxar regimens achieved high levels of platelet inhibition . A transient elevation in liver transaminases and dose-dependent QTc prolongation without apparent complications were observed in higher-dose atopaxar treatment groups . Conclusions — In this dose-ranging study of patients with CAD , treatment with atopaxar result ed in platelet inhibition , more minor bleeding , and numerically but not statistically fewer ischemic events . Larger-scale trials are needed to determine whether these patterns translate into clinical ly meaningful effects . Clinical Trial Registration — URL : http://www . Clinical Trials.gov . Unique identifier : NCT00312052 Dual antiplatelet therapy ( DAPT ) , the combination of aspirin and a P2Y12 inhibitor , given for 12 months remains the st and ard of care after presentation with acute coronary syndrome ( ACS ) because it has been shown to be associated with a significant reduction in ischemic events compared with aspirin monotherapy . The factor Xa inhibitor rivaroxaban was shown to be associated with a significant reduction in the composite of cardiovascular death , myocardial infa rct ion , and stroke , and result ed in a nominal reduction in cardiovascular death , when added to background DAPT in the ATLAS ACS 2-TIMI 51 trial ; however , there was excessive bleeding with this " triple-therapy " approach . The combination of rivaroxaban with P2Y12 inhibition in a " dual-pathway " approach may be an effective therapeutic regimen for the treatment of ACS , given the known importance of P2Y12 inhibition after stenting and intriguing data that the combination of an anticoagulant with clopidogrel after stenting in patients with atrial fibrillation appears an attractive option to this patient population . GEMINI-ACS-1 is a prospect i ve , r and omized , double-dummy , double-blind , active-controlled trial that will assess the safety of dual antithrombotic therapy ( rivaroxaban [ 2.5 mg twice daily ] + P2Y12 inhibitor ) as compared with DAPT ( aspirin [ 100 mg ] + P2Y12 inhibitor ) within 10 days of an ACS event in 3,000 patients . Patients will be r and omized in a 1:1 ratio stratified by intended P2Y12 inhibitor use ( clopidogrel 75 mg daily or ticagrelor 90 mg twice daily ) , with 1500 patients expected in each P2Y12 inhibitor strata . The primary end point is Thrombolysis in Myocardial Infa rct ion clinical ly significant bleeding ( major , minor , or requiring medical attention ) . The exploratory efficacy determination will be a composite of cardiovascular death , myocardial infa rct ion , ischemic stroke , and stent thrombosis . GEMINI-ACS-1 will assess the safety and feasibility of dual antithrombotic therapy with rivaroxaban and a P2Y12 inhibitor compared with conventional DAPT for the treatment for patients with recent ACS BACKGROUND Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis . Since factor Xa plays a central role in thrombosis , the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months . The primary efficacy end point was a composite of death from cardiovascular causes , myocardial infa rct ion , or stroke . RESULTS Rivaroxaban significantly reduced the primary efficacy end point , as compared with placebo , with respective rates of 8.9 % and 10.7 % ( hazard ratio in the rivaroxaban group , 0.84 ; 95 % confidence interval [ CI ] , 0.74 to 0.96 ; P=0.008 ) , with significant improvement for both the twice-daily 2.5-mg dose ( 9.1 % vs. 10.7 % , P=0.02 ) and the twice-daily 5-mg dose ( 8.8 % vs. 10.7 % , P=0.03 ) . The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes ( 2.7 % vs. 4.1 % , P=0.002 ) and from any cause ( 2.9 % vs. 4.5 % , P=0.002 ) , a survival benefit that was not seen with the twice-daily 5-mg dose . As compared with placebo , rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting ( 2.1 % vs. 0.6 % , P<0.001 ) and intracranial hemorrhage ( 0.6 % vs. 0.2 % , P=0.009 ) , without a significant increase in fatal bleeding ( 0.3 % vs. 0.2 % , P=0.66 ) or other adverse events . The twice-daily 2.5-mg dose result ed in fewer fatal bleeding events than the twice-daily 5-mg dose ( 0.1 % vs. 0.4 % , P=0.04 ) . CONCLUSIONS In patients with a recent acute coronary syndrome , rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes , myocardial infa rct ion , or stroke . Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding . ( Funded by Johnson & Johnson and Bayer Healthcare ; ATLAS ACS 2-TIMI 51 Clinical Trials.gov number , NCT00809965 . ) BACKGROUND Despite current treatments , patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events . We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients . METHODS We r and omly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel ( 300 mg immediately , followed by 75 mg once daily ) ( 6259 patients ) or placebo ( 6303 patients ) in addition  to aspirin for 3 to 12 months . RESULTS The first primary outcome --a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group ( relative risk with clopidogrel as compared with placebo , 0.80 ; 95 percent confidence interval , 0.72 to 0.90 ; P<0.001 ) . The second primary outcome --the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group ( relative risk , 0.86 ; 95 percent confidence interval , 0.79 to 0.94 ; P<0.001 ) . The percentages of patients with in-hospital refractory or severe ischemia , heart failure , and revascularization procedures were also significantly lower with clopidogrel . There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group ( 3.7 percent vs. 2.7 percent ; relative risk , 1.38 ; P=0.001 ) , but there were not significantly more patients with episodes of life-threatening bleeding ( 2.2 percent [ corrected ] vs. 1.8 percent ; P=0.13 ) or hemorrhagic strokes ( 0.1 percent vs. 0.1 percent ) . CONCLUSIONS The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation . However , the risk of major bleeding is increased among patients treated with clopidogrel BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel ( a 60-mg loading dose and a 10-mg daily maintenance dose ) or clopidogrel ( a 300-mg loading dose and a 75-mg daily maintenance dose ) , for 6 to 15 months . The primary efficacy end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The key safety end point was major bleeding . RESULTS The primary efficacy end point occurred in 12.1 % of patients receiving clopidogrel and 9.9 % of patients receiving prasugrel ( hazard ratio for prasugrel vs. clopidogrel , 0.81 ; 95 % confidence interval [ CI ] , 0.73 to 0.90 ; P<0.001 ) . We also found significant reductions in the prasugrel group in the rates of myocardial infa rct ion ( 9.7 % for clopidogrel vs. 7.4 % for prasugrel ; P<0.001 ) , urgent target-vessel revascularization ( 3.7 % vs. 2.5 % ; P<0.001 ) , and stent thrombosis ( 2.4 % vs. 1.1 % ; P<0.0 
    Output:
    
Few combinations of antithrombotic therapy were associated with a reduction in mortality compared with aspirin monotherapy , highlighting the difficulty in clinical interpretation of composite ischemic endpoints .