***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 —Certain proton pump inhibitors ( PPIs ) interfere with clopidogrel metabolism , potentially attenuating P2Y12 receptor inhibition . Previous observational and r and omized trials report conflicting results regarding the clinical significance of this pharmacological interaction . We examined the interaction between concomitant administration of PPI and clopidogrel on platelet reactivity and clinical outcomes in the large-scale , prospect i ve Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents study . Methods and Results —On-treatment P2Y12 platelet reactivity testing was performed using the VerifyNow assay after clopidogrel loading and successful drug-eluting stent implantation at 11 sites in the United States and Germany .  PPIs were prescribed at the discretion of treating physicians ; patients were followed for 2 years . High platelet reactivity was defined as P2Y12 reactivity units > 208 . Of 8582 enrolled patients , 2697 ( 31.4 % ) were taking a PPI at the time of coronary intervention . After adjustment for differences in baseline characteristics , PPI use was independently associated with high platelet reactivity ( odds ratio , 1.38 : 95 % confidence interval , 1.25–1.52 , P=0.0001 ) . A total of 2162 ( 25.2 % ) patients were prescribed a  PPI at hospital discharge . In a propensity-adjusted multivariable analysis , discharge PPI use was independently associated with increased risk for postdischarge major adverse cardiac events ( cardiac death , myocardial infa rct ion , or ischemia-driven target lesion revascularization ) at 2-year follow-up ( hazard ratio , 1.21 ; 95 % confidence interval , 1.04–1.42 , P=0.02 ) . Conclusions —In patients treated with clopidogrel after successful drug-eluting stents implantation , the concomitant administration of PPI was associated with high platelet reactivity and a greater rate of adverse outcomes during long-term follow-up . Additional studies are warranted to determine the risk – benefit ratio of PPIs in patients with drug-eluting stents treated with clopidogrel . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00433966 BACKGROUND Omeprazole , usually used in the antiplatelet therapy during percutaneous coronary intervention ( PCI ) in acute coronary syndrome ( ACS ) , has been reported to increase ischemic events in retrospective studies . However , other clinical trials gave paradoxical results . The aim of this study was to assess the effects of omeprazole on clopidogrel efficacy and clinical events . METHODS All patients ( n = 172 ) received aspirin ( loading dose 300 mg and maintenance dose 100 mg/d ) and clopidogrel ( loading dose 600 mg and maintenance dose 75 mg/d ) during the therapy . They were r and omized to receive omeprazole ( 20 mg/d ) or placebo for 30 days . Residual platelet activities in the adenosine 5'-diphosphate ( ADP ) pathway were detected on the fifth day after PCI with thrombelastography (TEG)-mapping . The clinical events were recorded after one month . RESULTS According to the five levels of platelet activities , the frequency distributions of the inhibition rates were significantly different ( P = 0.0062 ) . However , no significant change was seen in the distribution among the highest or the lowest inhibiting levels ( > 95 % and < 30 % inhibition rate ) . And there were no significant differences ( P > 0.05 ) in events incidence , while gastro-intestinal bleeding decreased in co-administration of omeprazole . CONCLUSIONS Omeprazole significantly blunts clopidogrel efficacy while not exacerbates ischemic events in ACS undergoing PCI . Omeprazole even can decrease gastro-intestinal bleeding in those patients Background — The clinical significance of the interaction between clopidogrel and proton pump inhibitors ( PPIs ) remains unclear . Methods and Results — We examined the relationship between PPI use and 1-year cardiovascular events ( cardiovascular death , myocardial infa rct ion , or stroke ) in patients with acute coronary syndrome r and omized to clopidogrel or ticagrelor in a prespecified , nonr and omized subgroup analysis of the Platelet Inhibition and Patient Outcomes ( PLATO ) trial . The primary end point rates were higher for individuals on a PPI ( n=6539 ) compared with those not on a PPI ( n=12 060 ) at r and omization in both the clopidogrel ( 13.0 % versus 10.9 % ; adjusted hazard ratio [ HR ] , 1.20 ; 95 % confidence interval [ CI ] , 1.04–1.38 ) and ticagrelor ( 11.0 % versus 9.2 % ; HR , 1.24 ; 95 % CI , 1.07–1.45 ) groups . Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI ( PPI versus non-PPI gastrointestinal treatment : clopidogrel , HR , 0.98 ; 95 % CI , 0.79–1.23 ; ticagrelor , HR , 0.89 ; 95 % CI , 0.73–1.10 ) . In contrast , patients on no gastric therapy had a significantly lower primary end point rate ( PPI versus no gastrointestinal treatment : clopidogrel , HR , 1.29 ; 95 % CI , 1.12–1.49 ; ticagrelor , HR , 1.30 ; 95 % CI , 1.14–1.49 ) . Conclusions — The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel .  However , a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment . Therefore , in the PLATO trial , the association between PPI use and adverse events may be due to confounding , with PPI use more of a marker for , than a cause of , higher rates of cardiovascular events . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00391872 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 It remains unclear whether concomitant use of omeprazole attenuates platelet function as compared with that of famotidine in patients with acute coronary syndromes ( ACS ) who receive clopidogrel . METHODS AND RESULTS In this prospect i ve study , 130 ACS patients treated with aspirin and clopidogrel who underwent stent implantation were r and omly assigned to receive a Japanese st and ard dose of omeprazole 10 mg daily or famotidine 20 mg daily for at least 4 weeks . Between 14 and 28 days after enrollment , there was no significant difference in the platelet reactivity index ( PRI ) measured with vasodilator-stimulated phosphoprotein phosphorylation assay between the omeprazole group ( n=65 ) and famotidine group ( n=65 ) ( 55±17 % vs. 51±19 % ; P=0.26 ) . The cumulative rate of adverse cardiovascular events at 12 months was similar in the groups ( 13 % vs. 17 % ; P=0.81 ) . The PRI was similar ( 54.9±17.9 % vs. 54.0±17.8 % ; P=0.83 ) in the omeprazole group ( n=33 ) and the famotidine group ( n=39 ) among patients with ST-elevation myocardial infa rct ion ( STEMI ) . However , there was a trend toward a higher PRI ( 55.2±15.9 % vs. 46.4±19.4 % ; P=0.06 ) in the omeprazole group ( n=32 ) as compared with the famotidine group ( n=26 ) among patients without persistent ST-segment elevation ACS . CONCLUSIONS As compared with famotidine , concomitant use of low-dose omeprazole does not significantly attenuate the antiplatelet effects of clopidogrel in patients with ACS , especially in those with STEMI BACKGROUND Gastrointestinal complications are an important problem of antithrombotic therapy . Proton-pump inhibitors ( PPIs ) are believed to decrease the risk of such complications , though no r and omized trial has proved this in patients receiving dual antiplatelet therapy . Recently , concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel . METHODS We r and omly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo , in addition to aspirin . The primary gastrointestinal end point was a composite of overt or occult bleeding , symptomatic gastroduodenal ulcers or erosions , obstruction , or perforation . The primary cardiovascular end point was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , revascularization , or stroke . The trial was terminated prematurely when the sponsor lost financing . RESULTS We planned to enroll about 5000 patients ; a total of 3873 were r and omly assigned and 3761 were included in analyses . In all , 51 patients had a gastrointestinal event ; the event rate was 1.1 % with omeprazole and 2.9 % with placebo at 180 days ( hazard ratio with omeprazole , 0.34 , 95 % confidence interval [ CI ] , 0.18 to 0.63 ; P<0.001 ) . The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo ( hazard ratio , 0.13 ; 95 % CI , 0.03 to 0.56 ; P = 0.001 ) . A total of 109 patients had a cardiovascular event , with event rates of 4.9 % with omeprazole and 5.7 % with placebo ( hazard ratio with omeprazole , 0.99 ; 95 % CI , 0.68 to 1.44 ; P = 0.96 ) ; high-risk subgroups did not show significant heterogeneity . The two groups did not differ significantly in the rate of serious adverse events , though the risk of diarrhea was increased with omeprazole . CONCLUSIONS Among patients receiving aspirin and clopidogrel , prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding . There was no apparent cardiovascular interaction between clopidogrel and omeprazole , but our results do not rule out a clinical ly meaningful difference in cardiovascular events due to use of a PPI . ( Funded by Cogentus Pharmaceuticals ; Clinical Trials.gov number , NCT00557921 . ) BACKGROUND Proton pump inhibitors ( PPIs ) are frequently prescribed in combination with clopidogrel , but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel . We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention ( PCI ) and dual-antiplatelet therapy ( DAPT ) with clopidogrel plus aspirin .  METHODS AND RESULTS In the PRODIGY trial , 1,970 patients were r and omized to 6- or 24-month DAPT at 30 days from index procedure . Among them , 738 patients ( 37.5 % ) received PPI  ( mainly lansoprazole ; 90.1 % ) at the time of r and omization . Proton pump inhibitor users were older , were most likely to be woman , had a lower creatinine clearance , presented more frequently with acute coronary syndrome , and had a higher CRUSADE bleeding score . After adjustment , the primary efficacy end point ( composite of all-cause death , myocardial infa rct ion , and cerebrovascular accident ) was similar between no PPI and PPI users ( 9.2 % vs 11.5 % , adjusted hazard ratio [ HR ] 1.051 , 95 % CI 0.788 - 1.400 , P = .736 ) . Bleeding rates did not differ between the 2 groups ( Bleeding Academic Research Consortium type 2 , 3 , or 5 : adjusted HR 0.996 , 95 % CI 0.672 - 1.474 , P = .980 ) . Net clinical adverse events were also similar in no PPI and PPI patients ( 12.9 % vs 14.9 % , adjusted HR 0.99 , 95 % CI 0.772 - 1.268 , P = .93 ) . 
    Output:
    
Conclusion : Concomitant use of PPIs and clopidogrel has been proved not to be associated with elevated cardiovascular risks according to RCTs .