Aspirin and
P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and
cerebrovascular diseases. Gastrointestinal complications, including
ulcer and
bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant
proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by
aspirin and, even more so,
clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through hepatic
CYP2C19 between PPIs and
clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The FDA and the EMA sent a warning in 2010 discouraging the concomitant use of
clopidogrel with
omeprazole or
esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new
P2Y12 receptor antagonists,
ticagrelor and
prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal
bleeding, including advanced age, concurrent use of
anticoagulants,
steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori
infection. Like
vitamin K antagonists (VKAs), DOACs can determine gastrointestinal
bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose
dabigatran (150 mg bid),
rivaroxaban and high-dose
edoxaban (60 mg daily) are associated with a higher risk of GI
bleeding as compared with
apixaban and
warfarin. In patients taking oral
anticoagulant with GI risk factor, PPI could be recommended, even if usefulness of PPIs in these patients deserves further data. Helicobacter pylori should always be searched, and treated, in patients with history of
peptic ulcer disease (with or without complication). Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or
anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of
platelet inhibitors,
anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.