Hawkey C J, Karrasch J A, Szczepañski L, Walker D G, Barkun A, Swannell A J, Yeomans N D
Division of Gastroenterology, University Hospital, Nottingham, United Kingdom.
N Engl J Med. 1998 Mar 12;338(11):727-34. doi: 10.1056/NEJM199803123381105.
Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs.
In a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 microg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 microg of misoprostol twice daily, or placebo for six months.
At eight weeks, treatment was successful in 76 percent of the patients given 20 mg of omeprazole (233 of 308), 75 percent of those given 40 mg of omeprazole (237 of 315), and 71 percent of those given misoprostol (212 of 298). The rates of gastric-ulcer healing were significantly higher with 20 mg of omeprazole (but not 40 mg of omeprazole) than with misoprostol. Healing rates among patients with duodenal ulcers were higher with either dose of omeprazole than with misoprostol, whereas healing rates among patients with erosions alone were higher with misoprostol. More patients remained in remission during maintenance treatment with omeprazole (61 percent) than with misoprostol (48 percent, P=0.001) and with either drug than with placebo (27 percent, P<0.001). There were more adverse events during the healing phase in the misoprostol group than in the groups given 20 mg and 40 mg of omeprazole (59 percent, 48 percent, and 46 percent, respectively).
The overall rates of successful treatment of ulcers, erosions, and symptoms associated with NSAIDs were similar for the two doses of omeprazole and misoprostol. Maintenance therapy with omeprazole was associated with a lower rate of relapse than misoprostol. Omeprazole was better tolerated than misoprostol.
米索前列醇对非甾体抗炎药（NSAIDs）所致溃疡有效，但因腹泻和腹痛，耐受性往往较差。我们比较了奥美拉唑和米索前列醇在愈合及预防NSAIDs相关溃疡方面的疗效。
在一项双盲研究中，我们将935例需要持续NSAIDs治疗且胃或十二指肠有溃疡或10处以上糜烂（或两者皆有）的患者随机分组，分别于早晨口服20 mg或40 mg奥美拉唑，或每日4次口服200 μg米索前列醇。患者接受治疗4周，若未愈合则治疗8周。治疗成功定义为各部位无溃疡且糜烂少于5处，且消化不良症状不超过轻度。然后，我们将732例治疗成功的患者随机重新分配，分别接受每日20 mg奥美拉唑、每日2次200 μg米索前列醇或安慰剂的维持治疗，为期6个月。
8周时，接受20 mg奥美拉唑治疗的患者中有76%（308例中的233例）治疗成功，接受40 mg奥美拉唑治疗的患者中有75%（315例中的237例）治疗成功，接受米索前列醇治疗的患者中有71%（298例中的212例）治疗成功。20 mg奥美拉唑组（而非40 mg奥美拉唑组）胃溃疡愈合率显著高于米索前列醇组。两种剂量的奥美拉唑治疗十二指肠溃疡患者的愈合率均高于米索前列醇，而单纯糜烂患者中米索前列醇的愈合率更高。维持治疗期间，接受奥美拉唑治疗的患者缓解率（61%）高于接受米索前列醇治疗的患者（48%，P = 0.001），且接受任何一种药物治疗的患者缓解率均高于接受安慰剂治疗的患者（27%，P < 0.001）。米索前列醇组愈合期的不良事件多于20 mg和40 mg奥美拉唑组（分别为59%、48%和46%）。
两种剂量的奥美拉唑和米索前列醇治疗NSAIDs相关溃疡、糜烂及症状的总体成功率相似。奥美拉唑维持治疗的复发率低于米索前列醇。奥美拉唑的耐受性优于米索前列醇。
