***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: CONTEXT The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease , the leading cause of death among persons with diabetes . The independent effect of diabetes on mortality following acute coronary syndromes ( ACS ) is uncertain . OBJECTIVE To evaluate the influence of diabetes on mortality following ACS using a large data base spanning the full spectrum of ACS . DESIGN , SETTING , AND PATIENTS A subgroup analysis of patients with diabetes enrolled in r and omized clinical trials that evaluated ACS therapies .  Patients with ACS in 11 independent Thrombolysis in Myocardial Infa rct ion ( TIMI ) Study Group clinical trials from 1997 to 2006 were pooled , including 62,036 patients ( 46,577 with ST-segment elevation myocardial infa rct ion [ STEMI ] and 15,459 with unstable angina/non-STEMI [ UA/NSTEMI ] ) , of whom 10 613 ( 17.1 % ) had diabetes . A multivariable model was constructed to adjust for baseline characteristics , aspects of ACS presentation , and treatments for the ACS event . MAIN OUTCOME MEASURES Mortality at 30 days and 1 year following ACS among patients with diabetes vs patients without diabetes . RESULTS Mortality at 30 days was significantly higher among patients with diabetes than without diabetes presenting with UA/NSTEMI ( 2.1 % vs 1.1 % , P < .001 ) and STEMI ( 8.5 % vs 5.4 % , P < .001 ) . After adjusting for baseline characteristics and features and management of the ACS event , diabetes was independently associated with higher 30-day mortality after UA/NSTEMI ( odds ratio [ OR ] , 1.78 ; 95 % confidence interval [ CI ] , 1.24 - 2.56 ) or STEMI ( OR , 1.40 ; 95 % CI , 1.24 - 1.57 ) . Diabetes at presentation with ACS was associated with significantly higher mortality 1 year after UA/NSTEMI ( hazard ratio [ HR ] , 1.65 ; 95 % CI , 1.30 - 2.10 ) or STEMI ( HR , 1.22 ; 95 % CI , 1.08 - 1.38 ) . By 1 year following ACS , patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI ( 7.2 % vs 8.1 % ) . CONCLUSION Despite modern therapies for ACS , diabetes confers a significant adverse prognosis , which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease Background — The antiplatelet effects of the Platelet Inhibition and Patient Outcomes ( PLATO ) trial dose of ticagrelor in patients nonresponsive to clopidogrel and after they switch agents are unknown . Methods and Results — Patients with stable coronary artery disease on aspirin therapy  received a 300-mg clopidogrel load ; nonresponders were identified by light transmittance aggregometry . In a 2-way crossover design , nonresponders ( n=41 ) and responders ( n=57 ) r and omly received clopidogrel ( 600 mg/75 mg once daily ) or ticagrelor ( 180 mg/90 mg twice daily ) for 14 days during period 1 . In period 2 , all nonresponders switched treatment ; half of the responders continued the same treatment , whereas the others switched treatment . Inhibition of platelet aggregation was higher in nonresponders treated with ticagrelor compared with clopidogrel ( P<0.05 ) . Treatment with ticagrelor among nonresponders result ed in a > 10 % , > 30 % , and > 50 % decrease in platelet aggregation from baseline in 100 % , 75 % , and 13 % of patients , respectively . Platelet aggregation fell from 59±9 % to 35±11 % in patients switched from clopidogrel to ticagrelor and increased from 36±14 % to 56±9 % in patients switched from ticagrelor to clopidogrel ( P<0.0001 for both ) . Platelet reactivity was below the cut points previously associated with ischemic risk measured by light transmittance aggregometry , VerifyNow P2Y12 assay , and vasodilator-stimulated phosphoprotein phosphorylation in 98 % to 100 % of patients after ticagrelor therapy versus 44 % to 76 % of patients after clopidogrel therapy . Conclusions — Ticagrelor therapy overcomes nonresponsiveness to clopidogrel , and its antiplatelet effect is the same in responders and nonresponders . Nearly all clopidogrel nonresponders and responders treated with ticagrelor will have platelet reactivity below the cut points associated with ischemic risk . Clinical Trial Registration — http://www . clinical trials.gov . Unique Identifier : NCT00642811 OBJECTIVE It has been postulated that prasugrel might be the preferred treatment option in diabetes mellitus ( DM ) patients with acute coronary syndrome ( ACS ) undergoing percutaneous coronary intervention ( PCI ) . We aim ed to compare the pharmacodynamic action of ticagrelor versus prasugrel . RESEARCH DESIGN AND METHODS In a prospect i ve , single-center , single-blind , crossover study , 30 consecutive ACS patients with DM who had been pretreated with clopidogrel were r and omized to either 90 mg ticagrelor twice daily or 10 mg prasugrel once daily with a 15-day treatment period . Platelet reactivity ( PR ) was assessed with the VerifyNow P2Y12 function assay , measured in P2Y12 reaction units ( PRU ) . RESULTS PR was significantly lower after ticagrelor ( 45.2 PRU [ 95 % CI 27.4–63.1 ] ) compared with prasugrel ( 80.8 PRU [ 63.0–98.7 ] ) , with a least squares mean difference of –35.6 PRU ( −55.2 to −15.9 , P = 0.001 ) . High PR rate was 0 % for ticagrelor and 3.3 % for prasugrel ( P = 1.0 ) . CONCLUSIONS In DM patients with ACS who had been pretreated with clopidogrel and who undergo PCI , ticagrelor achieves a significantly higher platelet inhibition than prasugrel . Both antiplatelet agents effectively treat high PR . The relevance of these findings to the clinical efficacy and safety of ticagrelor and prasugrel in DM patients needs further elucidation Aims Patients with diabetes mellitus ( DM ) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM . Prasugrel , a more potent antiplatelet agent , is associated with greater reductions in ischaemic events compared with clopidogrel , particularly in patients with DM . The aim of this study was to perform serial pharmacodynamic assessment s of prasugrel with high-dose clopidogrel in patients with DM . Methods and results Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospect i ve , r and omized , double-blind , crossover study in patients with type 2 DM and coronary artery disease ( CAD ) . Patients ( n= 35 ) were r and omly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose ( MD ) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period . Platelet function was assessed by VerifyNow ® P2Y12 assay , light transmission aggregometry , and vasodilator-stimulated phosphoprotein phosphorylation at 0 , 1 , 4 , and 24 h and 7 days . Greater platelet inhibition by VerifyNow ® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD ( least squares mean , 89.3 vs. 27.7 % , P < 0.0001 ; primary endpoint ) . The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days ( P < 0.0001 ) . Similar results were obtained using all other platelet function measures . Prasugrel result ed in fewer poor responders at all time points irrespective of definition used . Conclusion In patients with type 2 DM and CAD , st and ard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel . Clinical trial identifier : www . clinical trials.gov — In acute coronary syndromes ( ACS ) , a dual antiplatelet regimen with an adenosine diphosphate ( ADP ) receptor antagonist plus aspirin has become the cornerstone of treatment . The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater , more rapid and consistent platelet inhibition compared to their predecessor clopidogrel . Based on their advantages over clopidogrel in two l and mark studies , both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation . Due to differences in ACS population s and conditions investigated , the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy can not be reliably estimated from independent trials . To date , no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists . The aim of this multicenter , r and omized , open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy Background —Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel . Direct pharmacodynamic comparison between them has not yet been reported in ST-segment – elevation myocardial infa rct ion patients . Methods and Results —In a prospect i ve , single-center , single-blind study , 55 out of 117 ( 47 % ) screened consecutive ST-segment – elevation myocardial infa rct ion patients undergoing primary percutaneous coronary intervention were r and omized to either ticagrelor 180 mg loading followed by 90 mg bid , or prasugrel 60 mg loading followed by 10 mg od for 5 days . Platelet reactivity ( PR ) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0 , 1 , 2 , 6 , 24 hours , and 5 days postr and omization . The primary end point , PR with VerifyNow at hour 1 , did not differ significantly between patients r and omized to ticagrelor versus prasugrel ( 257.3 P2Y12 reaction unit [ PRU ] , 95 % CI 230.8–283.8 versus 231.3 PRU , 95 % CI 205.3–257.4 ; P=0.2 ) . PR did not differ at 2 , 6 , and 24 hours , although at day 5 it was lower with ticagrelor than prasugrel ( 25.6 PRU , 95 % CI 12.3–38.9 versus 50.3 PRU , 95 % CI 36.4–64.1 ; P=0.01 ) . At hour 2 , high on-treatment PR rates ( cutoff 208 PRU ) were 46.2 % and 34.6 % for ticagrelor and prasugrel , respectively , decreased significantly thereafter , whereas did not differ significantly between the 2 agents at all the time points of the study . Conclusions —In patients with ST-segment – elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention , both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action . Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment – elevation myocardial infa rct ion . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01463163 BACKGROUND Patients ' responses to oral antiplatelet therapy  are subject to variation . Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy . METHODS We r and omly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring  , with drug adjustment in patients who had a poor response to antiplatelet therapy , or to a conventional strategy without monitoring and drug adjustment . The primary end point was the composite of death , myocardial infa rct ion , stent thrombosis , stroke , or urgent revascularization 1 year after stent implantation . For patients in the monitoring group , the  VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later . RESULTS In the monitoring group , high platelet reactivity in patients taking c 
    Output:
    
This meta- analysis shows the addition of a P2Y12 inhibitor is superior to placebo , with a trend favouring the use of prasugrel in patients with diabetes with ACS , particularly those undergoing PCI