PPIs: too much of a good thing?

Proton pump inhibitors (PPIs) are highly effective at suppressing gastric acid production. They are widely used for symptomatic relief from dyspepsia; offer benefits in patients with gastrointestinal ulcers and gastro-oesophageal reflux disease; and have an important prophylactic role when used with NSAIDs, aspirin and other drugs that can damage the gastrointestinal tract. The continued increase in PPI prescribing reflects the popularity of these drugs among prescribers and patients. For example, during the first quarter of 2010, over 9 million PPI prescriptions were issued in England, an increase of 79% compared to 2005.1 However, such heavy use also means that the undoubted advantages of PPIs must be balanced against accumulating published evidence suggesting harms associated with long-term use.

For instance, a report in 2009 from the Newcastle Regional Drug and Therapeutics Centre identified a possible increased likelihood of fractures in patients taking PPIs for over 1 year.2 Subsequently, an observational study, involving 130,487 postmenopausal women followed up for almost 8 years, found that PPIs were associated with a modest increase in the rate of spine, lower arm and total fractures (e.g. for total fractures, hazard ratio 1.25 (95% CI 1.15 to 1.36).3 (Whether osteoporosis is the mechanism for this increased fracture risk has been questioned.4)

In addition, a pharmacoepidemiological study of over 100,000 hospital discharges suggested that more intensive acid suppression increased the likelihood that hospital inpatients would develop nosocomial Clostridium difficile infection (e.g. by over 70% in those taking daily PPIs, compared with non-users).5 A further retrospective cohort study of 1,166 patients treated with antibiotics for C. difficile infection suggested that concurrent PPI use increased the likelihood of recurrence of the infection by around 40%.6

Also, a systematic review has suggested that the use of acid-suppressive drugs is associated with an increased risk …