***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 Clopidogrel is administered to prevent stent thrombosis ; however , the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described . Methods and Results Platelet aggregation ( 5 and 20 μmol/L ADP ) , the activation of glycoprotein IIb/IIIa ( PAC‐1 antibody ) , and the expression of P‐selectin were measured in patients undergoing elective coronary stenting ( n=96 ) at baseline and at 2 hours , 24 hours , 5 days , and 30 days after stenting . All patients received aspirin ( 325 mg ) . Clopidogrel ( 300 mg ) was administered in the catheterization laboratory and followed by 75 mg daily . There was marked interindividual variability in drug response as measured by all markers that showed a normal distribution . Resistance , defined as baseline aggregation ( % ) minus posttreatment aggregation ( % ) ≤10 % by 5 μmol/L ADP , was present in 31 % and 15 % of patients at 5 and 30 days , respectively . Patients with the highest pretreatment platelet reactivity remained the most reactive at 24 hours after treatment ( P<0.0001 ) . Conclusions Interindividual variability in the platelet inhibitory response  from clopidogrel occurs in patients undergoing elective coronary stenting . Patients with high pretreatment reactivity are least protected . Alternative pharmacological strategies and the association of adverse ischemic events should be investigated in these patients . ( Circulation . 2003 ; 107:2908‐2913 . Aim MULTIPRAC was design ed to provide insights into the use and outcomes associated with prehospital initiation of antiplatelet therapy with either prasugrel or clopidogrel in the context of primary percutaneous coronary intervention . After a previous report on efficacy and safety outcomes during hospitalization , we report here the 1-year follow-up data , including cardiovascular ( CV ) mortality . Methods and results MULTIPRAC is a multinational , prospect i ve registry of patients with ST-elevation myocardial infa rct ion ( STEMI ) from 25 hospitals in nine countries , all of which had an established practice of prehospital start of dual antiplatelet therapy in place . The key outcome was CV death at 1 year . Among 2,036 patients followed-up through 1 year , 49 died ( 2.4 % ) , 10 during the initial hospitalization and 39 within 1 year after hospital discharge . The primary analysis was based on the P2Y12-inhibitor , used from prehospital loading dose through hospital discharge . Prasugrel ( n=824 ) was more commonly used than clopidogrel ( n=425 ) . The observed 1-year rates for CV death were 0.5 % with prasugrel and 2.6 % with clopidogrel . After adjustment for differences in baseline characteristics , treatment with prasugrel was associated with a significantly lower risk of CV death than treatment with clopidogrel ( odds ratio 0.248 ; 95 % confidence interval 0.06–0.89 ) . Conclusion In STEMI patients from routine practice undergoing primary angioplasty , who were able to start oral antiplatelet therapy prehospital , treatment with prasugrel as compared to clopidogrel was associated with a lower risk of CV death at 1-year follow-up BACKGROUND Despite improvements in the emergency treatment of myocardial infa rct ion ( MI ) , early mortality and morbidity remain high . The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation , but its effects in patients with ST-elevation MI were unclear . METHODS 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were r and omly allocated clopidogrel 75 mg daily ( n=22,961 ) or matching placebo ( n=22,891 ) in addition to aspirin 162 mg daily . 93 % had ST-segment elevation or bundle branch block , and 7 % had ST-segment depression . Treatment was to continue until discharge or up to 4 weeks in hospital ( mean 15 days in survivors ) and 93 % of patients completed it . The two prespecified co- primary outcomes were : ( 1 ) the composite of death , reinfa rct ion , or stroke ; and ( 2 ) death from any cause during the scheduled treatment period . Comparisons were by intention to treat , and used the log-rank method . This trial is registered with Clinical Trials.gov , number NCT00222573 . FINDINGS Allocation to clopidogrel produced a highly significant 9 % ( 95 % CI 3 - 14 ) proportional reduction in death , reinfa rct ion , or stroke ( 2121 [ 9.2 % ] clopidogrel vs 2310 [ 10.1 % ] placebo ; p=0.002 ) , corresponding to nine ( SE 3 ) fewer events per 1000 patients treated for about 2 weeks . There was also a significant 7 % ( 1 - 13 ) proportional reduction in any death ( 1726 [ 7.5 % ] vs 1845 [ 8.1 % ] ; p=0.03 ) . These effects on death , reinfa rct ion , and stroke seemed consistent across a wide range of patients and independent of other treatments being used . Considering all fatal , transfused , or cerebral bleeds together , no significant excess risk was noted with clopidogrel , either overall ( 134 [ 0.58 % ] vs 125 [ 0.55 % ] ; p=0.59 ) , or in patients aged older than 70 years or in those given fibrinolytic therapy . INTERPRETATION In a wide range of patients with acute MI , adding clopidogrel 75 mg daily to aspirin and other st and ard treatments ( such as fibrinolytic therapy ) safely reduces mortality and major vascular events in hospital , and should be considered routinely This r and omized , active-controlled , double-blind study assessed the pharmacodynamics , pharmacokinetics and safety of ticagrelor in Japanese patients and a smaller cohort of non-Japanese Asian patients . The study recruited patients aged 20–80 years who had received aspirin 75–100 mg/day for ≥2 weeks and had percutaneous coronary intervention or acute coronary syndrome > 3 months previously . Patients received 4 weeks ’ treatment with ticagrelor 45 mg bid , ticagrelor 90 mg bid or clopidogrel 75 mg qd ( all with aspirin ) . The inhibition of platelet aggregation ( IPA , final-extent ) and pharmacokinetics of ticagrelor were assessed on days 1 and 28 . Overall , 139 Asian patients were r and omized  ( ticagrelor 45 mg bid , n = 50 ; ticagrelor 90 mg bid , n = 43 ; clopidogrel , n = 46 ) of whom 118 were Japanese . Mean final-extent IPA was greater with ticagrelor 90 mg bid versus ticagrelor 45 mg bid and with both ticagrelor doses versus clopidogrel . At the end of the dosing interval on day 28 , mean final-extent IPA was 10.0 % higher ( 95 % confidence interval 0.5–19.5 % ) for ticagrelor 90 mg bid versus ticagrelor 45 mg bid , 15.1 % higher ( 5.8–24.4 % ) for ticagrelor 45 mg bid versus clopidogrel , and 25.1 % higher ( 15.5–34.7 % ) for ticagrelor 90 mg bid versus clopidogrel . In Japanese patients , exposure to ticagrelor and its active metabolite AR-C124910XX increased dose-proportionally . The safety profile of ticagrelor was consistent with previous studies . Ticagrelor was associated with enhanced IPA versus clopidogrel in Japanese patients 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 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 
    Output:
    
Conclusions : Based on this meta- analysis , newer P2Y12 inhibitors were significantly more effective than clopidogrel in the events of myocardial infa rct ion and cardiovascular death in patients with ACS , although the incidence of thrombosis in MI-defined bleeding was higher compared with clopidogrel