Gastrointestinal protection with proton pump inhibitors in cardiovascular patients: still misunderstood and underutilised

Despite randomised clinical trial data, there has been long-standing controversy and debate about whether proton pump inhibitors (PPIs) raise ischaemic risk in the context of dual antiplatelet therapy. Some observational studies have suggested an association between PPI use and higher rates of ischaemic events, but these studies were all confounded by the fact that sicker patients were the ones being prescribed the PPIs. An insightful analysis from the Veterans Affairs Healthcare System showed the potential misclassification of angina as gastro-oesophageal reflux, with PPI use essentially serving as a proxy for undetected and untreated coronary artery disease in some cases1. The prior observational studies were, in part, undertaken because of the suggestion in platelet function studies of an interaction between clopidogrel and PPIs, in particular older PPIs such as omeprazole. However, these pharmacokinetic and pharmacodynamic interactions have not consistently been shown to predict cardiovascular outcomes2. In fact, the randomised COGENT trial in acute coronary syndrome and stented patients demonstrated no increase in ischaemic events during the critical 6 months after presentation in patients receiving both clopidogrel and omeprazole but,...