Title

 

Authors

M. Tuccori
 
Unit of Pharmacology, University Hospital of Pisa, Italy

 

Abstract

Despite their effectiveness in the treatment of pathological conditions associated with pain/inflammation and in cardiovascular prevention (i.e. low-dose aspirin), non-steroidal anti-inflammatory drugs (NSAIDs) are burdened with several adverse effects, among which upper gastrointestinal (GI) events are the most common. Clinical guidelines recommend the concomitant use of NSAIDs and gastroprotective drugs (proton pump inhibitors or misoprostol), or the use of coxibs alone in patients at risk for GI complications.  In this setting, PPIs have gained wide diffusion among other gastroprotective strategies, due to their effectiveness and favorable tolerability profile. However, several studies have reported inappropriate PPI prescription/utilization patterns, including underutilization in patients with upper GI risk, use of inappropriate doses, overuse in patients without risk factors, use in combination with other gastroprotective approaches and persistent use after NSAID discontinuation. Underuse has been observed in several investigations. Particularly, Dutch studies showed that, in the period from 1996 to 2005, the pattern of PPIs prescription for gastroprotection did not correlate with that of NSAID use. Among patients with at least one risk factor, only 10.9% received any type of prophylaxis, and, among patients with two or more risk factors, only 14.8% received gastroprotective therapies. Of note, an increase in the percentage of patients receiving prophylaxis has been reported overtime both for patients with one risk factor (7.5% in 1996; 27.9% in 2002) and those with two or more risk factors (8.4% in 1996; 36.1% in 2002; 43.6% in 2005). Results from these studies are consistent with those obtained in other countries. For instance, in the period 2000-2002, a USA study found that, among patients at risk for NSAID-associated upper GI injury, about 30% received either a coxib or a combination of NSAID plus PPI. In another USA investigation, only 27.2% of patients at risk and 41.8% of those with more than 3 risk factors received NSAIDs with adequate gastroprotection, including PPIs, in adherence with published guidelines. With regards for the use of PPIs in combination with other gastroprotective approaches, an USA study, conducted on a veteran population, noted that more than 50% of patients receiving a PPI were treated concomitantly with a coxib, despite current evidence supports a benefit from combining a PPI with a coxib only in patients at very high risk for GI complications. The issue of dosage inadequacy has been addressed in a Dutch study, in which 7% of PPI users received doses below the minimum recommended/effective dose for NSAID-associated ulcer prophylaxis. As far as overuse is concerned, the main reason for inappropriate PPI use is prophylaxis in low-risk patients. Although this circumstance has been documented particularly for stress ulcer prophylaxis, an inappropriate protection with PPI for NSAID-induced GI-injury has been estimated in 6.2% of patients at hospital discharge in a recent German study. Finally, unnecessary prolongation of PPI therapy after NSAID discontinuation has been documented in The Netherlands. Indeed, a primary care study observed that 30% of patients was prescribed PPIs in amounts sufficient to cover a treatment period of over 2 months after NSAID discontinuation. Overall, the prescription of PPIs to prevent NSAID-associated upper GI injury remains largely inappropriate. Educational programs and audits focused on the appropriate prescription of PPIs should be implemented by national health authorities to properly manage the prophylaxis of NSAID-induced upper GI injury with PPIs.
 
References
Lanas A, Ferrandez A. (2007) Inappropriate prevention of NSAID-induced gastrointestinal events among long-term users in the elderly. Drugs Aging 24,121-131
Ahrens D et al., (2010) Appropriateness of treatments recommendations for PPI in hospital discharge letters. Eur J Clin Pharmacol 66:1265-1271.