***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 and Purpose — Evidence suggests that some proton pump inhibitors can attenuate the antiplatelet effect of clopidogrel . The significance of this potential drug interaction in patients with cerebrovascular disease is unknown . Methods — We conducted a nested case-control study of all Ontario residents aged ≥66 years newly treated with clopidogrel after a stroke between April 1 , 2002 , and September 30 , 2008 . In the primary analysis , case patients were those readmitted for stroke , and a secondary analysis examined all-cause mortality . For each case , up to 4 event-free control subjects were matched on age , gender , and outcome type ( stroke or transient ischemic attack ) . Exposure to proton pump inhibitors was categorized as current ( within 60 days ) , previous ( 61 to 180 days ) , or remote ( 181 to 365 days ) . Results — Among 2765 patients entering the cohort , we identified 118 cases readmitted for stroke and 472 control subjects . After multivariable adjustment , current use of proton pump inhibitors was not associated with a significantly increased risk of recurrent stroke ( adjusted odds ratio , 1.05 ; 95 % CI , 0.60 to 1.82 ) or death ( adjusted odds ratio , 1.84 ; 95 % CI , 0.88 to 3.89 ) . Conclusions — As a class , proton pump inhibitors are not associated with an increased risk of recurrent stroke or death among older patients treated with clopidogrel after stroke Background — Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting , a substantial number of incidents continue to occur . Methods and Results — The antiplatelet effect of clopidogrel was studied prospect ively in 60 consecutive patients who underwent primary angioplasty ( percutaneous coronary intervention [ PCI ] ) with stenting for acute ST-segment – elevation myocardial infa rct ion ( STEMI ) to determine whether variability in response to clopidogrel affects clinical outcomes . Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation . Although patients in the first quartile were resistant to the effects of clopidogrel ( ADP-induced platelet aggregation at day 6 , 103±8 % of baseline ) , ADP-induced aggregation was reduced to 69±3 % , 58±7 % , and 33±12 % of baseline , respectively , in patients in quartiles 2 through 4 ( P < 0.01 for all ) . In addition , epinephrine-induced platelet aggregation and platelet aggregation under flow conditions , assessed by the cone- and -plate(let ) analyzer method , were reduced significantly less in the first quartile than in quartiles 2 through 4 . Whereas 40 % of patients in the first quartile sustained a recurrent cardiovascular event during a 6-month follow-up , only 1 patient ( 6.7 % ) in the second quartile and none in the third and fourth quartiles suffered a cardiovascular event ( P = 0.007 ) . Conclusions — Up to 25 % of STEMI patients undergoing primary PCI with stenting are resistant to clopidogrel and therefore may be at increased risk for recurrent cardiovascular events 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 CONTEXT In adults with acute coronary syndrome , decreased platelet inhibition associated with concomitant use of clopidogrel and proton pump inhibitors ( PPI ) has been reported . OBJECTIVE To evaluate platelet activity associated with PPI + clopidogrel vs. clopidogrel alone in children enrolled in the Platelet Inhibition in Children On cLOpidogrel ( PICOLO ) trial of clopidogrel in children with a cardiac condition at risk for arterial thrombosis . DESIGN Patients 0 - 24 m r and omized to active therapy in the PICOLO trial were included in the present analysis . Platelet aggregation inhibition at baseline and steady state were evaluated in patients taking clopidogrel + PPI vs. clopidogrel only in the overall cohort and sub-group of clopidogrel responders . RESULTS A total of 49 patients were included ( 44 clopidogrel only , five clopidogrel + PPI ) ; median age 38 days ( interquartile range [ IQR ] 17 - 157 days ) . The majority of patients in each group had undergone systemic-to-pulmonary artery shunt .  Compared with the clopidogrel group , patients in the clopidogrel + PPI group had a trend toward lower percent inhibition of maximum extent of platelet aggregation overall ( median 6 % , IQR 0 - 44 % vs. 49 % , IQR 19 - 63 % , P= 0.09 ) , and a significant reduction in the clopidogrel responders sub-group ( median 25 % , IQR 3 - 45 % vs. 53 % , IQR 38 - 65 % , P= 0.04 ) . There was no difference in percent inhibition of rate of platelet aggregation . CONCLUSIONS Concomitant use of PPI + clopidogrel may be associated with decreased platelet inhibition in children with cardiac disease . Further study in a larger population and assessment of associated clinical outcomes is warranted 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 We aim ed to determine the prevalence of gastroesophageal reflux disease ( GERD ) and associated risk factors , and assess quality of life ( QoL ) in relation to the frequency and severity of reflux symptoms . Methods A r and om sample of 10 
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We performed a literature search for relevant original studies and systematic review s. PPIs likely affect the antiplatelet activity of clopidogrel as measured in vitro , and this may be a class effect .
We conclude that the pharmacodynamic effect has not been translated into any clinical ly meaningful adverse effect .
PPI cotherapy reduces the incidence of recurrent peptic ulcer and of upper gastrointestinal bleeding among patients on clopidogrel