Gastroprotection in patients on antiplatelet and/or anticoagulant therapy: a position paper of National Association of Hospital Cardiologists (ANMCO) and the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO)

Eur J Intern Med. 2021 Mar:85:1-13. doi: 10.1016/j.ejim.2020.11.014. Epub 2020 Dec 2.


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.

Keywords: anticoagulant therapy; antiplatelet therapy; direct oral anticoagulants; gastrointestinal bleeding; proton pump inhibitors, Helicobacter pylori.

Publication types

  • Review

MeSH terms

  • Anticoagulants / adverse effects
  • Cardiologists*
  • Gastroenterologists*
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology
  • Helicobacter Infections* / complications
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori*
  • Hospitals
  • Humans
  • Italy
  • Platelet Aggregation Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use


  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors