Scheiman James M, Yeomans Neville D, Talley Nicholas J, Vakil Nimish, Chan Francis K L, Tulassay Zsolt, Rainoldi Jorge L, Szczepanski Leszek, Ung Kjell-Arne, Kleczkowski Dariusz, Ahlbom Henrik, Naesdal Jørgen, Hawkey Christopher
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Am J Gastroenterol. 2006 Apr;101(4):701-10. doi: 10.1111/j.1572-0241.2006.00499.x. Epub 2006 Feb 22.
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.
质子泵抑制剂可降低非甾体抗炎药（NSAID）使用者溃疡复发率，但对于目前正在使用各类处方药的溃疡风险患者，其影响尚未明确界定。我们评估了埃索美拉唑对服用NSAID（包括COX-2抑制剂）的高危患者（年龄≥60岁和/或有溃疡病史）预防溃疡的效果。鉴于对COX-2抑制剂使用者心血管不良事件的担忧可能促使重新评估其使用情况，此类研究尤为重要。
我们进行了两项相似的双盲、安慰剂对照、随机、多中心研究；VENUS（美国）和PLUTO（跨国）。共有844例和585例需要每日服用NSAID（包括COX-2抑制剂）的患者被随机分为接受埃索美拉唑（20或40毫克）或安慰剂治疗，每日一次，共6个月。
在VENUS研究中，生命表估计6个月内发生溃疡的患者比例（主要变量，意向性治疗人群），安慰剂组为20.4%，埃索美拉唑20毫克组为5.3%（p<0.001），埃索美拉唑40毫克组为4.7%（p<0.0001）。在PLUTO研究中，这些值分别为安慰剂组12.3%，埃索美拉唑20毫克组5.2%（p = 0.018），埃索美拉唑40毫克组4.4%（p = 0.007）。非选择性NSAID使用者和COX-2抑制剂使用者均观察到显著降低。使用COX-2抑制剂的患者（n = 400）的合并溃疡发生率，安慰剂组为16.5%，埃索美拉唑20毫克组为0.9%（p<0.001），埃索美拉唑40毫克组为4.1%（p = 0.002）。埃索美拉唑耐受性良好，与安慰剂相比，症状控制更好。
对于高危患者，埃索美拉唑对长期使用NSAID（包括COX-2抑制剂）的患者预防溃疡有效。
