The reason for using funnel plots was the fact that studies with a smaller volume were used. For patients included in the self controlled case series analysis, follow-up is not censored at the occurrence of the event, as later exposed and unexposed periods of time need to be included in the analysis. Proton pump inhibitors PPIs are often used with clopidogrel to prevent gastrointestinal bleeding, however, some evidence suggests that PPIs may interfere with the activation of clopidogrel and diminish its antiplatelet effect.
This median duration was imputed for all individual prescriptions where duration was not recorded. Short term adverse clinical outcomes associated with the concomitant use of clopidogrel and PPIs.
Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: As clopidogrel and aspirin can both increase the risk of bleeding, a proton pump inhibitor is often co-prescribed to help reduce the risk of gastrointestinal bleeding.
Gargiolo [ 16 ].
Such confounding can be difficult to overcome in non-randomised studies of drug use. Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel.
Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: For this study, complete data on all incident myocardial infarctions recorded in the project were available from 1 January to 31 July In the secondary analysis, in which we restricted the definition of proton pump inhibitor to only those known to be strong inhibitors of CYP 2C19, the results obtained were similar table 3.
The primary outcome was a composite end point of all cause mortality or incident myocardial infarction. The first was a traditional cohort design, and the second was a self controlled case series design. The subset of linked General Practice Research Database practices is broadly similar in profile to the full complement of practices, suggesting generalisability is maintained when the linked practices alone are used.
Publication bias was assessed by observing funnel plots. Evidence to date has been conflicting; some studies have observed an increased risk of vascular events in patients receiving clopidogrel and proton pump inhibitors, 1 3 4 5 while others, including an underpowered randomised trial, found no increased risk. The adjusted hazard ratios for other outcomes were 1. In addition, 37 more articles were eliminated since they were published before the year Follow-up time was then classified according to whether the patient was receiving a proton pump inhibitor as recorded in the database, with time updated treatment status, allowing patients to fluctuate between exposed and unexposed depending on prescription patterns.
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World J Gastrointest Pharmacol Ther ; 6: For each participant within the cohort we identified all of those with at least one incident myocardial infarction during their follow-up time as defined above. Dual antiplatelet therapy MACEs: Mortality was determined from Office for National Statistics mortality records, with incident myocardial infarction determined by Myocardial Ischaemia National Audit Project records.
During follow-up, use of proton pump inhibitor was sporadic in some patients and started later on in others. Taken together, a plausible explanation for our results is that the increased risk of both vascular and non-vascular harmful outcomes seen in patients receiving proton pump inhibitors and other long term drugs could be caused by confounding between people.
To account for possible bias from event dependent observation censoring we performed an analysis restricted to patients who were still alive three months after their first myocardial infarction during the observation period. PM Ho et al.