Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors.

Abstract

OBJECTIVES:

Proton pump inhibitors reduce ulcer recurrence in non-steroidal anti-inflammatory drug (NSAID) users, but their impact in at-risk ulcer-free patients using the current spectrum of prescribed agents has not been clearly defined. We assessed esomeprazole for ulcer prevention in at-risk patients (> or = 60 yr and/or ulcer history) taking NSAIDs, including COX-2 inhibitors. Such studies are particularly relevant, given that concerns regarding adverse cardiovascular outcomes among COX-2 inhibitor users may prompt re-evaluation of their use.

METHODS:

We conducted two similar double-blind, placebo-controlled, randomized, multicenter studies; VENUS (United States) and PLUTO (multinational). A total of 844 and 585 patients requiring daily NSAIDs, including COX-2 inhibitors were randomized to receive esomeprazole (20 or 40 mg) or placebo, daily for 6 months.

RESULTS:

In the VENUS study, the life table estimated proportion of patients who developed ulcers over 6 months (primary variable, intent-to-treat population) was 20.4% on placebo, 5.3% on esomeprazole 20 mg (p < 0.001), and 4.7% on esomeprazole 40 mg (p < 0.0001). In the PLUTO study, the values were 12.3% on placebo, 5.2% with esomeprazole 20 mg (p = 0.018), and 4.4% with esomeprazole 40 mg (p = 0.007). Significant reductions were observed for users of both non-selective NSAIDs and COX-2 inhibitors. Pooled ulcer rates for patients using COX-2 inhibitors (n = 400) were 16.5% on placebo, 0.9% on esomeprazole 20 mg (p < 0.001) and 4.1% on esomeprazole 40 mg (p= 0.002). Esomeprazole was well tolerated and associated with better symptom control than placebo.

CONCLUSIONS:

For at-risk patients, esomeprazole was effective in preventing ulcers in long-term users of NSAIDs, including COX-2 inhibitors.

• Authors: James M Scheiman, Neville D Yeomans, Nicholas J Talley, Nimish Vakil, Francis K L Chan, Zsolt Tulassay, Jorge L Rainoldi, Leszek Szczepanski, Kjell-Arne Ung, Dariusz Kleczkowski, Henrik Ahlbom, Jørgen Naesdal, Christopher Hawkey
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 101 Issue 4 Pg. 701-10 (Apr 2006) ISSN: 0002-9270 [Print] United States
• PMID: 16494585 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Anti-Ulcer Agents
• Cyclooxygenase 2 Inhibitors
• Proton Pump Inhibitors
• Esomeprazole

Topics

• Aged
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, therapeutic use)
• Anti-Ulcer Agents (therapeutic use)
• Arthritis, Rheumatoid (drug therapy)
• Cyclooxygenase 2 Inhibitors (adverse effects, therapeutic use)
• Double-Blind Method
• Duodenal Ulcer (chemically induced, prevention & control)
• Esomeprazole (therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Osteoarthritis (drug therapy)
• Proton Pump Inhibitors
• Risk Factors
• Stomach Ulcer (chemically induced, prevention & control)