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Should PPIs be given with clopidogrel in acute coronary syndrome?

Patients with acute coronary syndrome treated with clopidogrel plus a PPI had a significantly increased risk of death or rehospitalisation compared with those who did not receive a PPI.

A total of 8,205 patients with acute coronary syndrome who were taking clopidogrel at discharge, were enrolled in a retrospective cohort study between 2003 and 2006. The main outcome measure was all-cause mortality or rehospitalisation for acute coronary syndrome. There were 8,205 patients taking clopidogrel at discharge and 5,244 (64%) were also prescribed a PPI either at discharge or at some point thereafter.

The results showed that 615 patients (21%) died or were hospitalised for acute coronary syndrome in the clopidogrel without PPI group compared with 1,561 (30%) in the clopidogrel with PPI group. Subsequent multivariable analyses showed that clopidogrel and a PPI was associated with a significantly increased risk of death or rehospitalisation for acute coronary syndrome compared with clopidogrel without a PPI: odds ratio 1.25 (95% CI 1.11-1.41).

Clopidogrel is a common component of the standard treatment of acute coronary syndrome. Dual antiplatelet therapy with aspirin is recommended in both medically managed patients and those treated by percutaneous coronary intervention. Furthermore, if a coronary stent has been inserted the premature cessation of antiplatelet therapy could lead to catastrophic stent occlusion.

One of the main reasons for stopping antiplatelet therapy is upper gastrointestinal symptoms and as such PPIs are often used to improve patient acceptability of these antiplatelet regimens. Furthermore, they may even be prescribed prophylactically in those deemed to be at risk of upper gastrointestinal events. Therefore any potential interaction between clopidogrel and PPIs could be both commonplace and very significant in terms of coronary outcomes.

This study has demonstrated an important finding that needs to be verified in a randomised controlled trial. It certainly provides food for thought and prescribing a PPI to the dyspeptic patient on clopidogrel post acute coronary syndrome may not be such a good idea after all. Certainly prophylactic use of a PPI in this setting should be discouraged until further evidence is available.

Ho PM, Maddox TM, Wang L et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009;301(9):937-944


Dr Peter Savill
GPwSI cardiology, Southampton

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