From the Guidelines
Non-steroidal anti-inflammatory drugs (NSAIDs) are the primary group of medications that cause gastric irritation necessitating proton pump inhibitor (PPI) therapy. Common NSAIDs include ibuprofen, naproxen, diclofenac, indomethacin, and aspirin, which inhibit cyclooxygenase enzymes, reducing protective prostaglandin production in the stomach lining, leading to increased acid damage and potential ulceration 1.
Key Points to Consider
- PPIs like omeprazole, esomeprazole, pantoprazole, and lansoprazole are typically added when patients require long-term NSAID therapy, especially those with additional risk factors such as advanced age, history of peptic ulcer disease, concurrent corticosteroid or anticoagulant use, or Helicobacter pylori infection.
- The use of traditional non-selective NSAIDs increases the risk of serious gastrointestinal complications by approximately 2.5–5-fold compared with patients not receiving these medications 1.
- Patients taking low-dose aspirin alone have an increase in risk of approximately 1.5–3-fold, and when low-dose aspirin users add a non-selective NSAID, the risk may increase by two- to four-fold when compared with the use of low-dose aspirin alone 1.
Recommendations for PPI Therapy
- The standard approach is to prescribe the lowest effective PPI dose for the duration of NSAID therapy, with typical regimens including omeprazole 20mg daily or pantoprazole 40mg daily taken before breakfast.
- Other medications that may benefit from PPI co-therapy include corticosteroids (particularly when used with NSAIDs), certain chemotherapy agents, and bisphosphonates.
Considerations for Specific Patient Groups
- Elderly patients, especially those 65 years or older, constitute the largest high-risk subset for NSAID-related gastrointestinal complications, with an estimated annual incidence of hospital admission for upper gastrointestinal events (UGIE) of 1.4% related to use of NSAIDs plus low-dose ASA versus 0.6% for low-dose ASA alone 1.
- Patients with a history of peptic ulcer disease or those taking concurrent corticosteroids or anticoagulants are also at increased risk and may benefit from PPI co-therapy.
From the Research
Group of Drugs Causing Gastric Irritation
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric irritation, necessitating the addition of Proton Pump Inhibitors (PPIs) 2, 3, 4, 5, 6
Mechanism of Gastric Irritation
- NSAIDs alter mitochondrial function, deplete ATP, and render cells vulnerable to oxidant stress, leading to gastrointestinal injury 6
- Inhibition of prostaglandin synthesis by NSAIDs delays cellular repair, contributing to gastric irritation 6
Prevention and Treatment of Gastric Irritation
- PPIs are effective in reducing ulcer complications and endoscopic peptic ulcers associated with NSAID use 2, 4
- Histamine H2-receptor antagonists can heal NSAID-related ulcers, but have a slower healing rate compared to PPIs 6
- Prostaglandin analogues, such as misoprostol, can prevent and treat NSAID-related damage by enhancing mucosal blood flow and bicarbonate secretion 6