***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 — 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 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 — 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 — The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation ( IPA ) .  Prasugrel is a new thienopyridine that is more potent than st and ard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease . The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown . Methods and Results — Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation – Thrombolysis in Myocardial Infa rct ion 44 ( PRINCIPLE-TIMI 44 ) was a r and omized , double-blind , 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention . The primary end point of the loading-dose phase ( prasugrel 60 mg versus clopidogrel 600 mg ) was IPA with 20 & mgr;mol/L ADP at 6 hours . Patients with percutaneous coronary intervention entered the maintenance-dose phase , a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug . In this study , 201 subjects were r and omized . IPA at 6 hours was significantly higher in subjects receiving prasugrel ( mean±SD , 74.8±13.0 % ) compared with clopidogrel ( 31.8±21.1 % ; P<0.0001 ) . During the maintenance-dose phase , IPA with 20 & mgr;mol/L ADP was higher in subjects receiving prasugrel ( 61.3±17.8 % ) compared with clopidogrel ( 46.1±21.3 % ; P<0.0001 ) . Results were consistent across all key secondary end points ; significant differences emerged by 30 minutes and persisted across all time points . Conclusions — Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention , loading with 60 mg prasugrel result ed in greater platelet inhibition than a 600-mg clopidogrel loading dose . Maintenance therapy with prasugrel 10 mg/d result ed in a greater antiplatelet effect than 150 mg/d clopidogrel OBJECTIVES Our goal was to compare the safety and initial efficacy of AZD6140 , the first reversible oral adenosine diphosphate receptor antagonist , with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes ( NSTE-ACS ) . BACKGROUND AZD6140 achieves higher mean levels of platelet inhibition than clopidogrel in patients with stable coronary artery disease . METHODS A total of 990 patients with NSTE-ACS , treated with aspirin and st and ard therapy for ACS  , were r and omized in a 1:1:1 double-blind fashion to receive either twice-daily AZD6140 90 mg , AZD6140 180 mg , or clopidogrel 300-mg loading dose plus 75 mg once daily for up to 12 weeks . RESULTS The primary end point , the Kaplan-Meier rate of major or minor bleeding through 4 weeks , was 8.1 % in the clopidogrel group , 9.8 % in the AZD6140 90-mg group , and 8.0 % in the AZD6140 180-mg group ( p = 0.43 and p = 0.96 , respectively , vs. clopidogrel ) ; the major bleeding rates were 6.9 % , 7.1 % , and 5.1 % , respectively ( p = 0.91 and p = 0.35 , respectively , vs. clopidogrel ) . Although not statistically significant , favorable trends were seen in the Kaplan-Meier rates of myocardial infa rct ion ( MI ) over the entire study period ( MI : 5.6 % , 3.8 % , and 2.5 % , respectively ; p = 0.41 and p = 0.06 , respectively , vs. clopidogrel ) . In a post-hoc analysis of continuous electrocardiograms , mostly asymptomatic ventricular pauses > 2.5 s were more common , especially in the AZD6140 180-mg group ( 4.3 % , 5.5 % , and 9.9 % , respectively ; p = 0.58 and p = 0.01 , respectively , vs. clopidogrel ) . CONCLUSIONS This initial experience with AZD6140 in patients with ACS showed no difference in major bleeding but an increase in minor bleeding at the higher dose with encouraging results on the secondary end point of MI . This agent is currently being studied in a large outcomes trial in 18,000 patients with ACS 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 
    Output:
    
Our results suggest that ticagrelor allows a higher platelet reactivity inhibition as compared with prasugrel and leads to a further decrease in the rate of HTPR