***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 — Bleeding among patients with acute myocardial infa rct ion ( AMI ) is associated with worse long-term outcomes . Although the mechanism underlying this association is unclear , a potential explanation is that withholding antiplatelet therapies long beyond resolution of the bleeding event may contribute to recurrent events . Methods and Results — We examined medication use at discharge , 1 , 6 , and 12 months after AMI among 2498 patients in the Prospect i ve Registry Evaluating Myocardial Infa rct ion : Events and Recovery ( PREMIER ) registry . Bleeding was defined as non – coronary artery bypass graft – related Thrombolysis of Myocardial Infa rct ion major/minor bleeding or transfusion among patients with baseline hematocrit ≥28 % . Logistic regression was used to evaluate the association between bleeding during the index AMI hospitalization and medication use . In-hospital bleeding occurred in 301 patients ( 12 % ) with AMI . Patients with in-hospital bleeding were less likely to be discharged on aspirin or thienopyridine ( adjusted odds ratio=0.45 ; 95 % CI , 0.31 to 0.64 ; and odds ratio=0.62 ; 95 % CI , 0.42 to 0.91 , respectively ) . At 1 month after discharge , although patients with in-hospital bleeding remained significantly less likely to receive aspirin ( odds ratio=0.68 ; 95 % CI , 0.50 to 0.92 ) , use of thienopyridines in the 2 groups started to become similar . By 1 year , antiplatelet therapy use was similar among patients with and without bleeding . Postdischarge cardiology follow-up was associated with greater antiplatelet therapy use than either primary care or no clinical follow-up . Conclusions — Patients whose index AMI is complicated by bleeding are less likely to be treated with antiplatelet therapies during the first 6 months after discharge . Early re assessment of antiplatelet eligibility may represent an opportunity to reduce the long-term risk of adverse outcomes associated with bleeding BACKGROUND A substantial proportion of patients receiving fibrinolytic therapy for myocardial infa rct ion with ST-segment elevation have inadequate reperfusion or reocclusion of the infa rct -related artery , leading to an increased risk of complications and death . METHODS We enrolled 3491 patients , 18 to 75 years of age , who presented within 12 hours after the onset of an ST-elevation myocardial infa rct ion and r and omly assigned them to receive clopidogrel ( 300-mg loading dose , followed by 75 mg once daily ) or placebo . Patients received a fibrinolytic agent , aspirin , and when appropriate , heparin ( dispensed according to body weight ) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication . The primary efficacy end point was a composite of an occluded infa rct -related artery ( defined by a Thrombolysis in Myocardial Infa rct ion flow grade of 0 or 1 ) on angiography or death or recurrent myocardial infa rct ion before angiography . RESULTS The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group , representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy ( 95 percent confidence interval , 24 to 47 percent ; P<0.001 ) . By 30 days , clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes , recurrent myocardial infa rct ion , or recurrent ischemia leading to the need for urgent revascularization by 20 percent ( from 14.1 to 11.6 percent , P=0.03 ) . The rates of major bleeding and intracranial hemorrhage were similar in the two groups . CONCLUSIONS In patients 75 years of age or younger who have myocardial infa rct ion with ST-segment elevation and who receive aspirin and a st and ard fibrinolytic regimen , the addition of clopidogrel improves the patency rate of the infa rct -related artery and reduces ischemic complications OBJECTIVES Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies . Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice . This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies . METHODS The task force was appointed with the advice and consent of the Board of Directors of ISPOR . Members were experienced developers or users of models , worked in academia and industry , and came from several countries in North America and Europe . The task force met on three occasions , conducted frequent correspondence and exchanges of drafts by electronic mail , and solicited comments on three drafts from a core group of external review ers and more broadly from the membership of ISPOR . RESULTS Criteria for assessing the quality of models fell into three areas : model structure , data used as inputs to models , and model validation . Several major themes cut across these areas . Models and their results should be represented as aids to decision making , not as statements of scientific fact ; therefore , it is inappropriate to dem and that models be vali date d prospect ively before use . However , model assumptions regarding causal structure and parameter estimates should be continually assessed against data , and models should be revised accordingly . Structural assumptions and parameter estimates should be reported clearly and explicitly , and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses . CONCLUSIONS Model-based evaluations are a valuable re source for health-care decision makers . It is the responsibility of model developers to conduct modeling studies according to the best practicable st and ards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built 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<0.001 ) . Major bleeding was observed in 2.4 % of patients receiving prasugrel and in 1.8 % of patients receiving clopidogrel ( hazard ratio , 1.32 ; 95 % CI , 1.03 to 1.68 ; P=0.03 ) . Also greater in the prasugrel group was the rate of life-threatening bleeding ( 1.4 % vs. 0.9 % ; P=0.01 ) , including nonfatal bleeding ( 1.1 % vs. 0.9 % ; hazard ratio , 1.25 ; P=0.23 ) and fatal bleeding ( 0.4 % vs. 0.1 % ; P=0.002 ) . CONCLUSIONS In patients with acute coronary syndromes with scheduled percutaneous coronary intervention , prasugrel therapy was associated with significantly reduced rates of ischemic events , including stent thrombosis , but with an increased risk of major bleeding , including fatal bleeding . Overall mortality did not differ significantly between treatment groups . ( Clinical Trials.gov number , NCT00097591 [ Clinical Trials.gov ] . OBJECTIVES We sought to evaluate the long-term cost-effectiveness of clopidogrel for up to one year after an acute coronary syndrome ( ACS ) without ST-segment elevation . BACKGROUND The efficacy of platelet inhibition with clopidogrel for up to one year after ACS was demonstrated in the Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial , a r and omized trial of 12,562 patients in 28 countries that was conducted between 1998 and 2000 . Patients were given clopidogrel ( 300-mg load followed by 75 mg/day ) versus placebo , both in addition to aspirin , for a mean of nine months . METHODS We used patient-level clinical outcomes and re source use from the CURE trial and estimates of life expectancy gains as a result of the prevention of the clinical events of death , stroke , and myocardial infa rct ion on the basis of data from external sources . RESULTS Excluding clopidogrel costs , average costs of hospitalizations alone were 325 dollars less for the clopidogrel arm ( 95 % confidence interval -722 dollars to 45 dollars ) using diagnosis-related group-based Medicare reimbursement rates . When including clopidogrel costs ( 766 dollars greater for the clopidogrel arm ) , average total costs were 442 dollars higher for the clopidogrel arm ( 95 % confidence interval 62 dollars to 820 dollars ) . The incremental cost-effectiveness ratio ( ICER ) on the basis of the Framingham Heart Study was 6,318 dollars per life-year gained ( LYG ) with clopidogrel , with 94 % of bootstrap-derived ICER estimates < 50,000 dollars/LYG ; based on Saskatchewan , the ICER was 6,475 dollars/LYG with 98 % of estimates < 50,000 dollars . CONCLUSIONS Platelet inhibition with clopidogrel in patients for up to one year after presentation with an acute coronary syndrome is both effective and cost-effective OBJECTIVE To assess the long-term cost effectiveness of 1 year 's treatment with clopidogrel on top of st and ard therapy ( including aspirin ; ASA ) compared with st and ard therapy alone , in patients diagnosed with non-ST-segment-elevation acute coronary syndromes ( ACS ) in the UK . DESIGN Cost utility analysis using a Markov model , incorporating clinical data from CURE ( a multicentre r and omised 
    Output:
    
RESULTS Cost-effectiveness ratios were most sensitive to changes in the efficacy of dual antiplatelet therapy and reference-case model assumptions about costs beyond the trial period .
Sensitivity analyses in the cost-effectiveness studies of dual oral antiplatelet therapy were not fully adherent with HTA guidelines .