Prevention of Ulcers by Esomeprazole in At-Risk Patients Using Non-Selective NSAIDs and COX-2 Inhibitors

TLDR

Proton pump inhibitors reduce ulcer recurrence in NSAID users, yet their benefit for at‑risk ulcer‑free patients on modern NSAIDs and COX‑2 inhibitors remains unclear, especially amid cardiovascular safety concerns. The study evaluated esomeprazole for ulcer prevention in at‑risk patients aged ≥60 or with prior ulcer history who used NSAIDs, including COX‑2 inhibitors. Two double‑blind, placebo‑controlled, randomized multicenter trials (VENUS in the U.S. and PLUTO multinational) enrolled 1,429 patients on daily NSAIDs or COX‑2 inhibitors, who were randomized to esomeprazole 20 or 40 mg or placebo for six months.

Abstract

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