What is the role of Proton Pump Inhibitors (PPIs) in patients with chronic Non-Steroidal Anti-Inflammatory Drug (NSAID) use?

From the Guidelines

Proton pump inhibitors (PPIs) should be prescribed for all patients requiring chronic NSAID therapy who have risk factors for gastrointestinal complications, as they significantly reduce the risk of serious gastrointestinal complications like ulcers, bleeding, and perforation by approximately 50-60%. These risk factors include age over 65, history of peptic ulcer disease, concurrent use of anticoagulants or corticosteroids, and high-dose or multiple NSAID use 1. Standard PPI options include omeprazole 20mg daily, esomeprazole 20-40mg daily, pantoprazole 40mg daily, lansoprazole 30mg daily, or rabeprazole 20mg daily. The PPI should be taken once daily, typically before breakfast, for as long as NSAID therapy continues.

Some key points to consider when prescribing PPIs for chronic NSAID use include:

• The choice of NSAID associated with the lowest risk, and the use of the lowest effective NSAIDs dose can decrease risk 1
• H pylori eradication is a therapeutic option that will reduce NSAID-associated GI toxicity in, at least, a subset of patients 1
• Co-therapy with drugs that modify NSAID-induced pathogenic mechanisms, such as misoprostol, may also help, but its use is limited due to adverse effects 1
• Antisecretory therapy with H2-RA and PPI has been studied, and data indicate that H2-RA reduce the incidence of endoscopic duodenal, but not gastric ulcers in patients taking NSAIDs, while PPIs significantly reduce gastric and duodenal ulcers associated with NSAID use 1
• The combination of a COX-2 inhibitor with a PPI was associated with the greatest risk reduction for upper gastrointestinal complications 2

For patients without risk factors, PPIs are not routinely recommended but can be considered if symptoms of dyspepsia develop. PPIs work by irreversibly inhibiting the hydrogen-potassium ATPase pump in gastric parietal cells, reducing acid secretion and allowing the gastric mucosa to withstand NSAID-induced damage. Patients should be informed that common side effects may include headache, diarrhea, and nausea, while long-term use carries potential risks of vitamin B12 deficiency, hypomagnesemia, increased risk of fractures, and C. difficile infection.

From the Research

PPIs in Chronic NSAID Use

• The use of proton pump inhibitors (PPIs) in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) is a common practice to prevent gastrointestinal toxicity 3, 4, 5.
• PPIs have been shown to be effective in reducing the development of NSAID-associated ulcers and recurrent NSAID-related ulcer complications, as well as decreasing upper GI symptoms in NSAID users 3, 4.
• A systematic review of 31 trials found that PPIs were significantly more effective than placebo in reducing ulcer complications and endoscopic peptic ulcers, with no subgroup differences according to class of NSAIDs, ulcer risk, or age 4.
• The effectiveness of different PPIs in reducing ulcer complications and endoscopic peptic ulcers is generally similar, and PPIs significantly reduced gastrointestinal adverse events and related withdrawals compared to placebo 4.
• However, recent evidence suggests that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs, highlighting the need for careful consideration of the risks and benefits of coprescribing PPIs with NSAIDs 6.

Benefits and Risks of PPIs in NSAID Users

• PPIs have an excellent safety profile, and are beneficial in healing NSAID-induced ulcers and preventing their recurrence in patients requiring ongoing NSAID therapy 5.
• The use of a non-selective NSAID plus a PPI may be as effective in preventing NSAID gastropathy as celecoxib, and may be more cost-effective 7.
• However, the concomitant use of low-dose aspirin with any NSAID increases the risk of gastrointestinal complications, and diminishes the improved gastrointestinal safety profile of celecoxib 7.

Considerations for Clinicians

• Clinicians should carefully consider the risks and benefits of coprescribing PPIs with NSAIDs, and weigh the potential benefits against the potential risks of gastrointestinal toxicity and other complications 6, 7.
• Patients taking low-dose aspirin who have risk factors for GI complications should receive medical co-therapy, such as a PPI 3.
• The choice of PPI therapy should be based on individual patient needs and medical history, and should take into account the potential for drug-drug interactions and other safety considerations 5.