Randomized trial of low-dose misoprostol and naproxen vs. nabumetone to prevent recurrent upper gastrointestinal haemorrhage in users of non-steroidal anti-inflammatory drugs.
BACKGROUND
Prophylactic misoprostol or non-steroidal anti-inflammatory drugs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury.


OBJECTIVE
To compare nabumetone vs. co-therapy of naproxen with low-dose misoprostol for secondary prevention of upper gastrointestinal bleeding in NSAID users.


METHODS
NSAID users presenting with upper gastrointestinal bleeding were enrolled if they required long-term NSAIDs. After ulcer healing, they were randomized to receive: naproxen (500-1000 mg/day) and misoprostol (200 microg b.d.), or nabumetone (1000-1500 mg/day) and placebo misoprostol for 24 weeks. The primary end-point was recurrent upper gastrointestinal bleeding. The secondary end-point was the proportion of patients suffering from major gastrointestinal events including ulcer bleeding, symptomatic ulcers and severe dyspepsia.


RESULTS
A total of 90 patients were included in the intention-to-treat analysis (misoprostol/naproxen 45, nabumetone 45). Recurrent bleeding occurred in 10 patients (22.2%) receiving misoprostol/naproxen compared with three (6.7%) receiving nabumetone (relative risk 3.33, 95% CI: 0.98-11.32, P=0.069). The proportion of patients suffering from major gastrointestinal events at 24 weeks was 31.1% in the misoprostol/naproxen group and 28.9% in the nabumetone group.


CONCLUSIONS
Misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding. Neither low-dose misoprostol nor nabumetone is adequate for high-risk NSAID users.
Chan
F K
FK
Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong. fklchan@cuhk.edu.hk
Sung
J J
JJ
Ching
J Y
JY
Wu
J C
JC
Lee
Y T
YT
Leung
W K
WK
Hui
Y
Y
Chan
L Y
LY
Lai
A C
AC
Chung
S C
SC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002074:Butanones / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000008:administration & dosage*; D000077430:Nabumetone; D009288:Naproxen / Q000008:administration & dosage*; D011446:Prospective Studies; D012008:Recurrence
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D016595:Misoprostol; D009288:Naproxen; D000077430:Nabumetone