Prescribing proton pump inhibitors with clopidogrel

In a linked research paper (doi:10.1136/bmj.e4388), Douglas and colleagues analysed whether proton pump inhibitors (PPIs) influence the risk of adverse cardiovascular outcomes in users of aspirin and clopidogrel.1 The use of aspirin and clopidogrel, or dual antiplatelet treatment, is currently the standard of care for the prevention of coronary stent thrombosis.2 These drugs are also used in the management of other cardiovascular conditions.3 Although use of dual antiplatelet therapy is associated with an increased risk of gastrointestinal haemorrhage,4 this risk can be greatly reduced through the concomitant use of a PPI.5 However, clinicians have become worried about using PPIs with dual antiplatelet treatment after the discovery that PPIs may interfere with clopidogrel mediated platelet inhibition through inhibition of the CYP2C19 cytochrome pathway, which is necessary for activation of clopidogrel.6 In addition, the findings of observational studies suggest that PPIs are associated with an increased risk of adverse cardiac outcomes in users of dual antiplatelet treatment.7 However, given the inherent biases in observational datasets, it is unclear whether this …