Combining aspirin and proton pump inhibitors: for whom the warning bell tolls?

Aspirin and clopidogrel are well-known antiplatelet agents that are widely used across the spectrum of cardio- and cerebrovascular disease. Upper gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, many patients are also treated with a proton pump inhibitor (PPI). PPIs exert gastroprotection by raising intragastric pH. In recent years, it has been heavily discussed whether PPIs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Initially, pharmacodynamic and pharmacokinetic studies suggested a considerable drug interaction between PPIs and clopidogrel, and subsequent clinical studies were conducted to evaluate the clinical impact of this interaction. More recently, it has been reported that PPIs may also attenuate the antiplatelet effect of aspirin. This is particularly interesting, because a fixed combination of aspirin and a PPI (esomeprazole) has been developed and is currently under approval. Given the large number of patients taking aspirin and PPIs, even a small attenuation of the antiplatelet effect of aspirin may have substantial clinical impact. The present editorial summarizes current evidence on this drug interaction and discusses potential clinical implications.