Should patients with known coronary artery disease (CAD) on antiplatelet drugs after stent placement also take proton pump inhibitors (PPIs)?

From the Guidelines

Patients with known coronary artery disease on antiplatelet drugs after stent placement should take proton pump inhibitors (PPIs) if they have risk factors for gastrointestinal bleeding, as recommended by the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline 1. The use of PPIs in these patients is supported by the most recent evidence, which suggests that PPIs can reduce the risk of gastrointestinal bleeding associated with antiplatelet medications like aspirin and P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel) by decreasing gastric acid production. Some key risk factors for gastrointestinal bleeding that may warrant the use of PPIs include:

• History of peptic ulcer disease
• Advanced age (≥65 years)
• Concurrent use of anticoagulants or steroids
• H. pylori infection Common PPIs that may be used in these patients include omeprazole 20-40mg daily, pantoprazole 40mg daily, or esomeprazole 20-40mg daily, typically continued for the duration of dual antiplatelet therapy (DAPT) 1. It's worth noting that the decision to use PPIs should balance the reduced bleeding risk against potential side effects like vitamin B12 deficiency, hypomagnesemia, and slightly increased risk of C. difficile infection with long-term use, as highlighted in previous guidelines 1. However, the most recent guideline 1 takes precedence, and its recommendations should be followed in clinical practice. In patients on clopidogrel, pantoprazole or esomeprazole may be preferred over omeprazole due to fewer drug interactions, as suggested by earlier studies 1. Ultimately, the use of PPIs in patients with coronary artery disease on antiplatelet drugs after stent placement should be individualized based on the patient's risk factors and medical history, with the goal of minimizing the risk of gastrointestinal bleeding while also considering potential side effects.

From the Research

Benefits of Proton Pump Inhibitors (PPIs) in Patients with Coronary Artery Disease (CAD)

• The use of PPIs in patients with CAD on antiplatelet drugs after stent placement has been shown to reduce the risk of gastrointestinal events and significant bleeding from gastroduodenal lesions 2, 3, 4.
• A meta-analysis of 19 trials found that PPIs plus antithrombotic strategy could reduce the risk of gastrointestinal events (RR 0.34; 95% CI 0.21-0.54) and significant bleeding from gastroduodenal lesions (RR 0.09; 95% CI 0.03-0.28) in patients with CAD 2.
• Another study found that the use of PPIs was associated with a reduced risk of GI bleeding in patients treated with dual antiplatelet therapy after percutaneous coronary intervention or acute coronary syndrome 4.

Cardiovascular Outcomes

• The incidence of major adverse cardiovascular and cerebrovascular events (MACCE) did not increase significantly in patients receiving PPIs compared with patients without those (RR 1.05; 95% CI 0.96-1.15) 2.
• There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events, including myocardial infarction, stent thrombosis, and all-cause mortality 2, 4.
• A systematic review and meta-analysis found that the use of PPIs was not associated with an increased risk of MACEs or all-cause mortality in patients treated with dual antiplatelet therapy 4.

Risk Factors for Gastrointestinal Bleeding

• Advanced age, a history of peptic ulcer disease, co-administration of non-steroidal anti-inflammatory drugs, co-administration of anticoagulants, and physiological stress are considered to be the major risk factors for GI bleeding in patients undergoing antiplatelet therapy following PCI 5.
• The prevalence of GI bleeding in patients who are administered dual antiplatelet therapy following PCI is approximately 2%, and GI bleeding after PCI is associated with increased morbidity, mortality, duration of hospitalization, and cost 5.

Personalized Antiplatelet Therapies

• Personalized antiplatelet therapy has emerged as a paradigm that optimizes the balance between safety and efficacy by customizing treatment to the individual patient's needs and risk profile 6.
• Accurate risk stratification for both bleeding and thrombosis can aid in selecting the optimal antiplatelet therapy and prevent serious and life-threatening outcomes 6.