***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: Clopidogrel is used with aspirin as a st and ard combined treatment in patients with acute coronary syndrome . A proton pump inhibitor ( PPI ) is often administered to patients receiving antiplatelet therapy . However , PPI use with clopidogrel was recently shown to result in increased risk of major cardiovascular events when compared to clopidogrel use alone . Therefore , the aim of the present study was to evaluate the effects of omeprazole , a PPI , on the antiplatelet effect of clopidogrel . We divided 20 healthy volunteers into 2 groups ( n = 10 each ) . Twenty-four hours after a 300 mg loading dose of clopidogrel , one group received a dosage of 75 mg/day of clopidogrel and a placebo for 14 days , followed 3 weeks later by the same protocol but with coadministration of 75 mg/day clopidogrel and 20 mg/day omeprazole instead . The other group received the same treatment but in reverse order . Antiplatelet activity was assessed in terms of the P2Y12 reaction unit ( PRU ) and percentage inhibition using a VerifyNow P2Y12 assay system . The PRU of the omeprazole-treated subjects was significantly higher than that of the omeprazole-untreated subjects on day 14 ( 281.3 + /- 54.0 versus 240.0 + /- 72.2 , P = 0.048 ) . The percentage inhibition showed a decrease after the 14-day omeprazole treatment ( 22.7 + /- 29.9 % versus 35.1 + /- 18.7 % , P = 0.014 ) . Consequently , omeprazole reduces the antiplatelet effect of clopidogrel , suggesting that careful treatment planning is required when administering omeprazole to patients on clopidogrel therapy Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its variable biotransformation into the active metabolite . The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors , but the specific genes and mechanisms underlying clopidogrel bioactivation remain unclear . Using in vitro metabolomic profiling techniques , we identified paraoxonase-1 ( PON1 ) as the crucial enzyme for clopidogrel bioactivation , with its common Q192R polymorphism determining the rate of active metabolite formation . We tested the clinical relevance of the PON1 Q192R genotype in a population of individuals with coronary artery disease who underwent stent implantation and received clopidogrel therapy .  PON1 QQ192 homozygous individuals showed a considerably higher risk than RR192 homozygous individuals of stent thrombosis , lower PON1 plasma activity , lower plasma concentrations of active metabolite and lower platelet inhibition . Thus , we identified PON1 as a key factor for the bioactivation and clinical activity of clopidogrel . These findings have therapeutic implication s and may be exploited to prospect ively assess the clinical efficacy of clopidogrel Recent attention has been drawn to a potential drug-drug interaction observed between clopidogrel and proton pump inhibitors ( PPIs ) . However , this potential interaction may not be a class effect of PPIs . We investigated if pantoprazole , which has a different metabolism than omeprazole , diminishes the effectiveness of clopidogrel . Our study included 336 patients ( mean age 64.6 years ; 106 women ) 48 hours after percutaneous coronary stent implantation with a loading dose of 600 mg clopidogrel hydrogensulfate and 500 mg aspirin , followed by 75 mg clopidogrel and 100 mg aspirin daily  . Whereas 188 patients ( 59 women ) were not given any PPI comedication , 122 patients received pantoprazole and 26 either omeprazole or esomeprazole . The platelet aggregation followed by impedance aggregometry ( in Ohm ) was induced by 5 μmol/L adenosine diphosphate . The percentage of clopidogrel low-response ( CLR ) was similar between the non-PPI group [ 2.75 Ohm ( confidence interval , CI : 2.25 - 3.26 ) ; 21.9 % CLR ] and the pantoprazole group [ 2.33 Ohm ( CI : 1.79 - 2.87 ) ; 16.4 % CLR ] but higher in patients treated with omeprazole/esomeprazole ( 3.00 Ohm ( CI : 1.49 - 4.51 ) ; 30.8 % CLR ) . Multivariate regression analysis reveals that the risk of CLR in the pantoprazole comedication group was not increased compared with the group without any PPI [ odds ratio 0.59 ( CI : 0.31 - 1.13 ) 0.11 ] . Our data suggest that pantoprazole does not diminish the antiplatelet effectiveness of clopidogrel early after coronary stenting . Therefore , the use of pantoprazole seems preferable in patients treated with clopidogrel when a concomitant medication with a PPI is indicated 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 usually prescribed to patients undergoing dual antiplatelet therapy  to decrease the risk of gastrointestinal bleeding . Recent studies have raised concerns that PPIs could reduce clopidogrel 's efficacy by competitive inhibition of cytochrome P450 2C19 isoenzyme . All PPIs are metabolized by cytochrome P450 2C19 , although to varying degrees , and according to in-vitro studies , pantoprazole is the weakest inhibitor of this isoenzyme . We hypothesized that this drug interaction might not be a class effect . Methods One month after an acute myocardial infa rct ion 34 consecutive patients undergoing dual antiplatelet therapy were prospect ively analyzed .  Platelet function was measured ( VerifyNow system ) , in each patient , in three consecutive clinical scenarios : ( i ) first , after a 1-month washout period , without any PPI , ( ii ) after a 4-week period taking omeprazole 40 mg , and ( iii ) after another 1-month washout period , followed by 4-weeks taking pantoprazole 40 mg . In this crossover trial , patients were first r and omized to receive either omeprazole or pantoprazole . Results We observed a significant reduction in clopidogrel 's effect when patients were initiated with omeprazole ;  the mean P2Y12 reaction units ( PRU ) increased from 202±52 to 235±58 with omeprazole ( P<0.001 ) . With pantoprazole , clopidogrel efficacy was preserved ( PRU 215±54 , P=0.16 ) . Without any PPI , 26 % of patients were ‘ nonresponders ’ to clopidogrel ( PRU > 240 ) but when patients started omeprazole , this proportion increased to 45 versus 23 % with pantoprazole . Conclusion In this r and omized crossover study analyzing patients after acute myocardial infa rct ion , omeprazole coadministration showed a significant pharmacodynamic interaction with clopidogrel , whereas pantoprazole did not . These data suggest that the clopidogrel – PPIs drug interaction may not be a class effect Patients receiving dual antiplatelet treatment with aspirin and clopidogrel  are commonly treated with proton pump inhibitors ( PPIs ) . Attenuating effects on platelet response to clopidogrel have been reported solely for the PPI omeprazole . PPIs differ in their metabolisation properties as well as their potential for drug-drug interactions . The aim of this study was to investigate the impact of different PPIs ( pantoprazole , omeprazole , esomeprazole ) on platelet response to  clopidogrel  in patients with previous coronary stent placement under chronic clopidogrel treatment . In a cross-sectional observational study , consecutive patients under clopidogrel maintenance treatment ( n = 1,000 ) scheduled for a control coronary angiography were enrolled . Adenosine diphosphate (ADP)-induced platelet aggregation ( in AU*min ) was measured with multiple electrode platelet aggregometry ( MEA ) . From the entire study population , 268 ( 26.8 % ) patients were under PPI treatment at the time point of platelet function testing  ( pantoprazole , n = 162 ; omeprazole , n = 64 ; esomeprazole , n = 42 ) . Platelet aggregation ( median [ interquartile range ] ) was significantly higher in patients with omeprazole treatment ( 295.5 [ 193.5 - 571.2 ] AU*min ) compared to patients without PPI treatment ( 220.0 [ 143.8 - 388.8 ] AU*min ; p = 0.001 ) . Platelet aggregation was similar in patients with pantoprazole ( 226.0 [ 150.0 - 401.5 ] AU*min ) or esomeprazole ( 209.0 [ 134.8 - 384.8 ] AU*min ) treatment compared to patients without PPI treatment ( p = 0.69 and p = 0.88 , respectively ) . Attenuating effects of concomitant PPI treatment on platelet response to clopidogrel were restricted to the use of omeprazole . No attenuating effects on platelet response to clopidogrel were observed for pantoprazole or esomeprazole . Specifically design ed and r and omized clinical studies are needed to define the impact of concomitant PPI treatment on adverse events after percutaneous coronary intervention OBJECTIVES This study sought to compare the effect of 2 proton pump inhibitors ( PPIs ) on platelet response to clopidogrel after coronary stenting for non-ST-segment elevation acute coronary syndrome ( NSTE ACS ) . BACKGROUND Use of omeprazole has been reported to significantly decrease the clopidogrel antiplatelet effect because of cytochrome P450 interaction . Because all PPIs are metabolized by CYP2C19 , but to a varying degree , we hypothesized that the reported negative omeprazole-clopidogrel drug interaction may not be caused by a class effect . METHODS A total of 104 patients undergoing coronary stenting for NSTE ACS were prospect ively included and r and omized to omeprazole or pantoprazole 20 mg . They received at discharge 75-mg aspirin and 150-mg c 
    Output:
    
Conclusion : Platelet function studies do not demonstrate a clear or consistent interaction between clopidogrel and PPIs .
Consequently , platelet function data are of uncertain clinical relevance in determining the risk of an adverse cardiovascular interaction between PPIs and clopidogrel .