Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view

Table 3 Main guideline and consensus documents on gastroprotection in patients under antithrombotic treatment

Guideline/consensus documents	Year	Main recommendations
The joint United States guidelines of the American College of Cardiology Foundation, the American College of Gastroenterology, and the American Heart Association[139]	2008	Recommended the use of PPIs only in patients taking warfarin in combination with antiplatelet therapy and/or NSAIDs. It did not recommend the substitution of clopidogrel for LDA in high-risk patients to reduce the risk of recurrence ulcer bleeding
Focused update of the joint United States guidelines of the American College of Cardiology Foundation, the American College of Gastroenterology, and the American Heart Association[141]	2010	Recommended use of PPIs in patients taking DAPT and in those who have multiple risk factors for GIB
Position paper issued by Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists, and the Italian Federation of General Practitioners[33]	2016	Recommended the use of standard doses of PPIs for those taking antiplatelet agents (individually or in association) only if at least one risk factor is present (age > 65 yr, concomitant use of steroids or anticoagulants, previous history of peptic ulcer). In addition, the use of pantoprazole or rabeprazole was suggested if clopidogrel was used, while there were no restrictions on the choice of PPIs with prasugrel and ticagrelor
The ESC guidelines on DAPT[145]	2017	Recommended gastroprotection with PPIs in all patients
Maastricht/Florence Consensus report on management of Helicobacter pylori infection[146]	2017	Search for H. pylori should be performed in patients with a history of peptic disease who take NSAIDs or aspirin. However, there were no specific recommendations on LDA since the evidence was considered controversial; no recommendations were provided for non-aspirin antiplatelet agents and/or oral anticoagulants
Consensus of the American College of Gastroenterology on treatment of Helicobacter pylori infection[140]	2017	Suggested searching for the infection in patients starting aspirin therapy, even if it was emphasized that the basis for this recommendation was weak. No specific recommendations regarding non-aspirin antiplatelet agents and/or oral anticoagulants
ESC guidelines on non-ST-segment elevation acute coronary syndrome[144]	2020	Recommended (class I, level of evidence A), for pharmacological long-term management, concomitant use of PPIs in patients receiving aspirin monotherapy, DAPT, DAT, TAT, or OAC monotherapy who are at high risk of GIB. They suggested as a strategy to reduce bleeding risk related to percutaneous coronary intervention the use of PPIs in patients on DAPT at higher-than-average risk of gastrointestinal bleeds (i.e., history of gastrointestinal ulcer/haemorrhage, anticoagulant therapy, chronic NSAIDS/corticosteroid use, or two or more of: Age ≥ 65 yr; dyspepsia; gastro-oesophageal reflux disease; H. pylori infection; chronic alcohol use)
2020 ESC guidelines on the management of AF[147]	2020	Apixaban or dabigatran 110 mg bid is not associated with an excess of gastrointestinal bleeding compared with warfarin. It suggests the use of apixaban in patients with AF at high risk of bleeding from the GI tract
The Korean guidelines for the Clinical Guidelines for Drug-related Peptic Ulcer, revised under the Korean College of Helicobacter and Upper Gastrointestinal Research in 2020[143]	2020	Treatment for Helicobacter pylori infections is recommended in patients with a history of peptic ulcers and receiving long-term LDA therapy to prevent peptic ulcers and complications. The maintenance of anti-ulcer drugs, such as PPIs, is also recommended after H. pylori eradication if patients require other antiplatelet agents or anticoagulants. Regardless of H. pylori eradication, when patients with a history of peptic ulcer take long-term LDA, the concomitant use of a PPI according to the severity of the peptic ulcer is recommended
Gastroprotection in patients on antiplatelet and/or anticoagulant therapy: A position paper of the National Association of Hospital Cardiologists and the Italian Association of Hospital Gastroenterologists and Endoscopists[148]	2021	PPIs are recommended: In single antiplatelet therapy in presence of risk factors; in DAPT; in dual and triple antithrombotic therapy; in single anticoagulant therapy in presence of risk factors

H. pylori: Helicobacter pylori; AF: Atrial fibrillation; DAPT: Double antiplatelet therapy; DAT: Double antithrombotic therapy; GIB: Gastrointestinal bleeding; GI: Gastrointestinal; LDA: Low dose aspirin; OAC: Oral anticoagulant; PPI: Proton pump inhibitor; TAT: Triple antithrombotic therapy.