Anti-secretory agents - especially PPI - and nitrates reduce NSAID-associated GI bleeding

Anti-secretory agents - especially PPI - and nitrates reduce NSAID-associated GI bleeding

A large epidemiological study suggests that anti-secretory drugs reduce the risk of gastro-intestinal bleeding in patients taking NSAID, as do nitrates, however proton-pump inhibitors (PPI are much the most effective. The authors note that gastro-intestinal bleeding is a major risk with NSAID therapy, a problem for which various strategies are suggested. Use of COX-2 selective agents has been recommended, however drug withdrawals and reported cardiovascular problems with this group has reduced their popularity. Misoprostol has proven benefit, but is poorly tolerated by many people. Anti-secretory agents are widely used, but the evidence for their protective effects is weaker, and some experimental work suggests that organic nitrates may have clinically useful benefit.

This study was carried out to determine which agents were effective in reducing the risk of upper GI peptic ulcer bleeds associated with nonselective NSAIDs, aspirin and other antiplatelet agents, and anticoagulants. It was a case-control study, with prospective case determination and retrospective data collection, carried out during 2001 to 2004 and using data collected from Spanish hospital associated with a gastroenterology network. Cases were adults hospitalised with confirmed upper GI peptic ulcer bleeding: each case was matched with two controls by age, hospital and admission month, admitted or seen in outpatients for any condition not related to NSAID use, any GI bleeding, and cardiovascular or joint diseases. Cases and controls were classified as having a history of ulcer, dyspepsia, or neither. Current relevant drug use included NSAID, aspirin or other antiplatelet drugs, anticoagulants, PPI, histamine-2 receptor antagonists, and any nitrate.

A total of 2,777 patients were matched with 5,532 controls. Unsurprisingly, use of NSAID (including aspirin) was associated with increased risk of peptic ulcer bleeding, as was use of antiplatelet agents and anticoagulants. PPI, histamine-2 blockers, and nitrates all reduced the risk of peptic ulcer bleeding, with relative risks compare to non-use of 0.33, 0.65, and 0.52 respectively. Use of PPI was associated with greatest risk reductions for NSAID and antiplatelet drugs, however no agent reduced the risk with oral anticoagulants. There was no difference between omeprazole and other PPI.

Based on their analysis, the authors conclude that all three drug groups - PPI, histamine-2 blockers, and nitrates - reduce the risk of peptic ulcer bleeding in patients taking NSAID and antiplatelet drugs. PPI, however, gave the most marked and consistent reduction in risk. None of the drugs studied reduce the risk associated with oral anticoagulants.

Am J Gastroenterol 2007;102:507-15 (link to abstract); from Reuters Health for 25th April 2007, via Medscape (free registration required)