What are the risks and management strategies for chronic proton pump inhibitor (PPI) use in elderly patients?

Risks of Chronic PPI Use in the Elderly

Chronic PPI use in elderly patients increases risk of Clostridium difficile infection, bone fractures, hypomagnesemia, and vitamin B12 deficiency, and should be limited to the lowest effective dose for the shortest duration necessary to treat proven indications. 1, 2, 3

Major Adverse Effects in Elderly Populations

Infectious Complications

• Clostridium difficile-associated diarrhea (CDAD) is significantly increased with PPI therapy, particularly in hospitalized elderly patients 2, 3. This risk necessitates consideration of CDAD in any elderly patient on PPIs who develops diarrhea that does not improve 2.
• Community-acquired pneumonia has been associated with PPI use in observational studies, with higher doses showing stronger associations 1, 4.

Musculoskeletal Risks

• Osteoporosis-related fractures of the hip, wrist, and spine are increased with long-term PPI therapy (≥1 year) and high-dose regimens (multiple daily doses) 2, 3. The elderly are particularly vulnerable given their baseline fracture risk 1.
• Patients at risk for osteoporosis should be managed according to established treatment guidelines while on PPIs 2, 3.

Metabolic and Nutritional Deficiencies

• Hypomagnesemia can occur after ≥3 months of PPI therapy, potentially causing tetany, arrhythmias, and seizures 3. For elderly patients on prolonged therapy or taking digoxin/diuretics, magnesium monitoring should be considered before and during treatment 3.
• Vitamin B12 (cyanocobalamin) deficiency may develop with acid suppression lasting >3 years due to hypo- or achlorhydria 2, 3. This is particularly concerning in the elderly who may already have marginal B12 stores 4.
• Iron deficiency can result from reduced intestinal absorption 5.

Renal Complications

• Acute tubulointerstitial nephritis (TIN) can occur at any point during PPI therapy, presenting with varying signs from hypersensitivity reactions to non-specific decreased renal function 2, 3. PPIs should be discontinued immediately if TIN is suspected 2, 3.
• Chronic kidney disease has been associated with long-term PPI exposure in observational studies 6, 4.

Autoimmune Manifestations

• Cutaneous and systemic lupus erythematosus have been reported with PPIs, occurring from weeks to years after initiation 2, 3. Subacute cutaneous lupus erythematosus (SCLE) is the most common form 2, 3. If signs or symptoms develop, discontinue the PPI and refer for specialist evaluation 2, 3.

Cardiovascular and Neurological Concerns

• Dementia has been associated with long-term PPI use in observational studies of elderly populations 6, 4.
• Increased mortality signals have been identified in studies examining long-term PPI exposure 6.

Clinical Management Strategies

Indication Assessment

All elderly patients on chronic PPIs should have their indication reviewed and documented. 1 Without an ongoing appropriate indication, PPIs can only cause harm through pill burden, costs, and adverse effects 1.

• Definite indications for long-term use include: Barrett's esophagus, severe erosive esophagitis (LA grade C/D), gastroprotection in high-risk NSAID/aspirin users, and secondary prevention of peptic ulcers 1.
• Not indicated for long-term use: nonerosive reflux disease without sustained PPI response, uninvestigated dyspepsia, or empiric treatment of laryngopharyngeal symptoms 1.

Gastroprotection Considerations

PPIs are appropriate for elderly patients on antithrombotic therapy who have multiple risk factors for GI bleeding. 1 High-risk features include:

• History of upper GI bleeding 1
• Multiple antithrombotic agents (anticoagulants plus antiplatelets) 1
• Age >60 years with aspirin/NSAID use 1
• Concurrent corticosteroid use 1

For patients on dual antiplatelet therapy or multiple antithrombotics, gastroprotection with PPIs should continue for as long as antithrombotic therapy is administered 1.

De-prescribing Approach

Elderly patients without definitive indications should be considered for trial of PPI discontinuation. 1

• Most patients with GERD have nonerosive disease and may not require chronic therapy 1.
• Patients on twice-daily dosing should be stepped down to once-daily before attempting discontinuation 1.
• Do not de-prescribe in patients with complicated GERD (severe erosive esophagitis, esophageal ulcer, peptic stricture) 1.

Important Caveats

• Avoid omeprazole and esomeprazole with clopidogrel due to CYP2C19 inhibition reducing clopidogrel's antiplatelet effect 2. Consider alternative PPIs or antiplatelet agents 2.
• Rebound acid hypersecretion may occur upon PPI discontinuation, causing transient upper GI symptoms 1. Patients should be counseled about this expected phenomenon 1.
• The European Society of Cardiology designates PPIs as potentially inappropriate medications (PIMs) in older people when used >12 weeks without documented chronic disease or ongoing risk factors 1.

Monitoring Recommendations

• Use the minimum effective dose for the shortest duration appropriate to the condition 1, 2, 3.
• Periodically reassess the clinical rationale for continued use 1.
• Consider magnesium monitoring in patients on prolonged therapy, especially those taking digoxin or diuretics 3.
• Evaluate for vitamin B12 deficiency if clinical symptoms develop after prolonged use 2, 3.