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All PPIs may have adverse effect on clopidogrel patients

By Nigel Praities

All types of proton-pump inhibitors increase the risk of a major cardiovascular event in patients taking clopidogrel, researchers claim.

And their new data refutes earlier claims that pantoprazole is a safer option in these patients.

The third major study to point to such an association shows a 51% increase in the risk of hospitalisation from events such as hearts attacks , stroke and unstable angina, in patients on clopidogrel taking PPIs, compared with those not taking PPIs.

The European drug regulator says it is reviewing safety data after three studies have shown an association.

Previous studies have suggested pantoprazole could be less harmful than other commonly used PPIs, but this trial showed it had the strongest association with cardiovascular hospitalisation, with an increased risk of 29% and that the risks were a ‘class effect' common to all types.

The study of the insurance records of 33,000 patients after coronary stent surgery – presented in a late-breaking session at the American Society for Cardiovascular Angiography and Interventions (SCAI) meeting earlier this month – prompted calls for GPs to consider prescribing alternative treatments to PPIs.

Dr Erick Stanek, a researcher on the study and senior director of research at Medco Health Solutions, New Jersey, said they found all PPIs as a class were associated with worse outcomes when used with the antiplatelet drug, unlike previous studies.

‘Concomitant use of clopidogrel with PPIs as a class, and … individually after coronary stenting, were associated with a significantly increased risk of hospitalization for major adverse cardiovascular events compared to clopidogrel alone,' he said.

The FDA recently launched a safety investigation into the interactions between the drugs, as PPIs are commonly prescribed for long periods to counteract the GI effects of antiplatelet therapy after major procedures like coronary stenting.

SCAI rushed out a statement recommending doctors should consider using H-blockers or antacids, rather than PPIs in patients on clopidogrel.

'The interventional cardiologist is advised to contact the patient's primary care provider or gastroenterologist to discuss treatment alternatives to PPIs,' it reads.

Dr Patrick Ward-Booth, a GP in Chelmsford, Essex and a member of the Primary Care Society for Gastroenterology, said GPs should review patients on both drugs.

‘Gastric bleeding in elderly patients is a risky business, so if they have an indication then you need to treat them. But as patients get re-prescribed, GPs should check whether they should be on both PPIs and clopidogrel,' he recommended.

A spokesperson from the European Medicines Agency said a committee would look at this issue at a meeting next week.

‘The EMEA is aware of the concerns. All available data are currently being evaluated, and the issue will be discussed at the next meeting of the agency's Committee for Medicinal Products for Human Use,' she said.

This is the latest concern over clopidogrel, coming a year after a study suggested high-risk patients who suddenly stopped taking it were more likely to suffer death or an MI within the subsequent 90 days

Growing evidence for PPI-clopidogrel interaction

Jan 2009 – Canadian researchers claim PPI use effectively ‘turns off' clopidogrel, after their study showed PPIs were responsible for 14% of all readmissions for an MI after 90 days of discharge in patients taking clopidogrel and a PPI

March 2009 – JAMA study in 8,205 patients with acute coronary syndrome found prescribing clopidogrel in addition to omeprazole raised the risk of death or rehospitalisation by 25%, compared with those not taking PPIs

May 2009 – US study of 33,000 insurance records shows a 51% increase in risk of hospitalisation for a major cardiovascular event in patients taking clopidogrel after coronary stent surgery alongside a PPI


Sources: Can Med Assoc J 2009; 180: 713 - 718; JAMA. 2009; 301: 937-44; SCAI 2009, abstract number P-177

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