***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: BACKGROUND Elderly patients are at high risk of ischaemic and bleeding events . Platelet function monitoring offers the possibility to individualise antiplatelet therapy to improve the therapeutic risk-benefit ratio . We aim ed to assess the effect of platelet function monitoring with treatment adjustment in elderly patients stented for an acute coronary syndrome . METHODS We did this multicentre , open-label , blinded-endpoint , r and omised controlled superiority study at 35 centres in France . Patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome were r and omly assigned ( 1:1 ) , via a central interactive voice-response system based on a computer-generated permuted-block r and omisation schedule with r and omly selected block sizes , to receive oral prasugrel 5 mg daily with dose or drug adjustment in case of inadequate response ( monitoring group ) or oral prasugrel 5 mg daily with no monitoring or treatment adjustment ( conventional group ) . R and omisation was stratified by centre . Platelet function testing was done 14 days after r and omisation and repeated 14 days after treatment adjustment in patients in the monitoring group . Study investigators and patients were not masked to treatment allocation , but allocation was concealed from an independent clinical events committee responsible for endpoint adjudication . The primary endpoint was a composite of cardiovascular death , myocardial infa rct ion , stroke , stent thrombosis , urgent revascularisation , and Bleeding Academic Research Consortium-defined bleeding complications ( types 2 , 3 , or 5 ) at 12 months ' follow-up . We did analysis by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01538446 . FINDINGS Between March 27 , 2012 , and May 19 , 2015 , we r and omly assigned 877 patients to the monitoring group ( n=442 ) or the conventional group ( n=435 ) . The primary endpoint occurred in 120 ( 28 % ) patients in the monitoring group compared with 123 ( 28 % ) patients in the conventional group ( hazard ratio [ HR ] , 1·003 , 95 % CI 0·78 - 1·29 ; p=0·98 ) . Rates of bleeding events did not differ significantly between groups . INTERPRETATION Platelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome . Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations . Our study does not support this practice or these recommendations . FUNDING Eli Lilly and Company , Daiichi Sankyo , Stentys , Accriva Diagnostics , Medtronic , and Fondation Coeur et Recherche Objective To develop a clinical risk prediction tool for estimating the cumulative six month risk of death and death or myocardial infa rct ion to facilitate triage and management of patients with acute coronary syndrome . Design Prospect i ve multinational observational study in which we used multivariable regression to develop a final predictive model , with prospect i ve and external validation . Setting Ninety four hospitals in 14 countries in Europe , North and South America , Australia , and New Zeal and . Population 43 810 patients ( 21 688 in derivation set ; 22 122 in validation set ) presenting with acute coronary syndrome with or without ST segment elevation enrolled in the global registry of acute coronary events ( GRACE ) study between April 1999 and September 2005 . Main outcome measures Death and myocardial infa rct ion . Results 1989 patients  died in hospital , 1466 died between discharge and six month follow-up , and 2793 sustained a new non-fatal myocardial infa rct ion . Nine factors independently predicted death and the combined end point of death or myocardial infa rct ion in the period from admission to six months after discharge : age , development ( or history ) of heart failure , peripheral vascular disease , systolic blood pressure , Killip class , initial serum creatinine concentration , elevated initial cardiac markers , cardiac arrest on admission , and ST segment deviation . The simplified model was robust , with prospect ively vali date d C-statistics of 0.81 for predicting death and 0.73 for death or myocardial infa rct ion from admission to six months after discharge . The external applicability of the model was vali date d in the data set from GUSTO IIb ( global use of strategies to open occluded coronary arteries ) . Conclusions This risk prediction tool uses readily identifiable variables to provide robust prediction of the cumulative six month risk of death or myocardial infa rct ion . It is a rapid and widely applicable method for assessing cardiovascular risk to complement clinical assessment and can guide patient triage and management across the spectrum of patients with acute coronary syndrome Background — Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies . In the Platelet Inhibition and Patient Outcomes ( PLATO ) trial , ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death , myocardial infa rct ion , and stroke at 12 months but with similar major bleeding rates . Methods and Results — Central laboratory serum creatinine levels were available in 15 202 ( 81.9 % ) acute coronary syndrome patients at baseline , and creatinine clearance , estimated by the Cockcroft Gault equation , was calculated . In patients with chronic kidney disease ( creatinine clearance < 60 mL/min ; n=3237 ) , ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3 % from 22.0 % ( hazard ratio [ HR ] , 0.77 ; 95 % confidence interval [ CI ] , 0.65 to 0.90 ) with an absolute risk reduction greater than that of patients with normal renal function ( n=11 965 ) : 7.9 % versus 8.9 % ( HR , 0.90 ; 95 % CI , 0.79 to 1.02 ) . In patients with chronic kidney disease , ticagrelor reduced total mortality ( 10.0 % versus 14.0 % ; HR , 0.72 ; 95 % CI , 0.58 to 0.89 ) . Major bleeding rates , fatal bleedings , and non – coronary bypass – related major bleedings were not significantly different between the 2 r and omized groups ( 15.1 % versus 14.3 % ; HR , 1.07 ; 95 % CI , 0.88 to 1.30 ; 0.34 % versus 0.77 % ; HR , 0.48 ; 95 % CI , 0.15 to 1.54 ; and 8.5 % versus 7.3 % ; HR , 1.28 ; 95 % CI , 0.97 to 1.68 ) . The interactions between creatinine clearance and r and omized treatment on any of the outcome variables were nonsignificant . Conclusions — In acute coronary syndrome patients with chronic kidney disease , ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non – procedure-related bleeding . Clinical Trial Registration — URL : http://www.clinicatrials.gov . Unique identifier : NCT00391872 Aims : We aim ed to study the relationship of chronic kidney disease stages with long-term ischemic and bleeding outcomes in medically managed acute coronary syndrome patients and the influence of more potent antiplatelet therapies on platelet reactivity by chronic kidney disease stage . Methods and results : We estimated creatinine clearance for 8953 medically managed acute coronary syndrome patients enrolled in the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial . Patients were classified by chronic kidney disease stage : normal renal function/mild ( creatinine clearance > 60 mL/min ) ; moderate ( creatinine clearance 30–60 mL/min ) ; severe ( creatinine clearance < 30 mL/min ) . Kaplan – Meier event rates through 30 months were evaluated for ischemic ( cardiovascular death , myocardial infa rct ion or stroke ; primary end point ) and bleeding ( Global Use of Strategies to Open Occluded Coronary Arteries and Thrombolysis In Myocardial Infa rct ion bleeding ) outcomes by chronic kidney disease stage and treatment allocation ( prasugrel vs. clopidogrel ) within each stage . Adjusted hazard ratios ( 95 % confidence intervals ) for moderate and for severe chronic kidney disease vs. normal/mild chronic kidney disease were estimated . Platelet reactivity at 30 days was assessed in a subset of patients ( n = 1947 ) . The majority of patients were in the normal/mild chronic kidney disease group ( 67 % ) , followed by moderate chronic kidney disease ( 29 % ) and severe chronic kidney disease ( 4 % ) . The incidence of ischemic and bleeding outcomes increased sharply across chronic kidney disease stages and no significant treatment interactions were observed . The adjusted risk of the primary end point increased across chronic kidney disease stages ( moderate vs. normal/mild : hazard ratio 1.26 ; 95 % confidence interval 1.09–1.46 ; severe vs. normal/mild : hazard ratio 1.60 ; 95 % confidence interval 1.25–2.04 ) . Platelet reactivity was lower in patients treated with prasugrel compared with clopidogrel , across all three chronic kidney disease stages . Conclusions : Among medically managed acute coronary syndrome patients , the long-term risks of ischemic and bleeding outcomes increased markedly with worse chronic kidney disease stages . Despite lower platelet reactivity of prasugrel compared with clopidogrel , no treatment interactions for ischemic and bleeding outcomes were observed Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background — Dual antiplatelet therapy in older versus younger patients with acute coronary syndromes is understudied . Low-dose prasugrel ( 5 mg/d ) is recommended for younger , lower-body-weight patients and elderly patients with acute coronary syndromes to mitigate the bleeding risk of st and ard-dose prasugrel ( 10 mg/d ) . Methods and Results — A total of 9326 medically managed patients with acute coronary syndromes from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes ( TRILOGY ACS ) trial ( < 75 years of age , n=7243 ; ≥75 years of age , n=2083 ) were r and omized to prasugrel ( 10 mg/d ; 5 mg/d for those ≥75 or < 75 years of age and < 60 kg in weight ) or clopidogrel ( 75 mg/d ) plus aspirin for ⩽30 months . A total of 515 participants ≥75 years of age ( 25 % of total elderly population ) had serial platelet reactivity unit measurements in a platelet-function sub study . Cumulative risks of the primary end point ( cardiovascular death/myocardial infa rct ion/stroke ) and Thrombolysis in Myocardial Infa rct ion ( TIMI ) major bleeding increased progressively with age and were ≥2-fold higher in older participants . Among those ≥75 years of age , TIMI major bleeding ( 4.1 % versus 3.4 % ; hazard ratio , 1.09 ; 95 % confidence interval , 0.57–2.08 ) and the primary end point rates were similar with reduced-dose prasugrel and clopidogrel . Despite a correlation between lower 30-day on-treatment platelet reactivity unit values and lower weight only in the prasugrel group , there was a nonsignificant treatment-by-weight interaction for platelet reactivity unit values among participants ≥75 years of age in the platelet-function sub study ( P=0.06 ) . No differences in weight were seen in all participants ≥75 years of age with versus without TIMI major/minor bleeding in both treatment groups . Conclusions — Older age is associated with substantially increased long-term cardiovascular risk and bleeding among patients with medically managed acute coronary syndromes , with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel compared with clopidogrel in elderly patients . No significant interactions among weight , pharmacodynamic response , and bleeding risk were observed between reduced-dose prasugrel and clopidogrel in elderly patients . Clinical Trial Registration — URL : http://www . clinical trials.gov/ct2/home . Unique identifier : NCT0069999 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- 
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Conclusions The effect of more potent P2Y12 inhibitors compared with clopidogrel  on efficacy and safety end points is consistent in elderly and younger patients .