Prescribing Advice for GPs

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PPI interaction with clopidogrel

The Journal of the Canadian Medical Association has published the results of a population-based study that aimed to assess the clinical importance of the interaction between proton pump inhibitors (PPIs) and clopidogrel.

Clopidogrel is metabolised by the liver to an active molecule that inhibits platelet aggregation however evidence is emerging that some PPIs inhibit this pathway and may increase the risk of adverse cardiac outcomes.

This research reviewed database records for 13,636 patients who were started on treatment with clopidogrel after an acute myocardial infarction between 2002 and 2007. 782 of these patients were readmitted within 90 days with a second event. Of this latter group, 734 patients were matched with 2,057 controls and analyses were performed for associations between usage of a PPI and cardiac events.

Patients who were readmitted were more likely to have co-morbidities such as heart failure, diabetes and renal failure. Despite this additional disease burden they were less likely to be prescribed ACE inhibitors, beta-blockers or statins.

After correcting for many factors this analysis found an increased risk in readmission in current users of PPIs (adjusted odds ratio 1.27, 95% CI 1.03-1.57). Further analysis found no correlation between readmission and H2-receptor agonists or in readmission among non-users of clopidogrel. It also seems that this interaction does not occur with pantoprazole.

Notable limitations of this study are the lack of data for some important cardiac risk factors including smoking status, blood pressure and lipid levels. Non-prescription medication data were also unavailable for the analysis.

The authors conclude that, "concomitant treatment with clopidogrel and proton pump inhibitors should be minimised". H2-receptor agonists are a suitable alternative and pantoprazole is suggested if a PPI is required.

Action: Clinicians should be aware of this interaction and the potential to increase cardiac events. Patients who take clopidogrel should be advised to avoid PPIs in favour of alternative treatments until further data are available on the clinical significance of this interaction.

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