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 dru gs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury. Aim: To compare nabumetone vs. co-therapy of naproxen with low-dose misopro stol for secondary prevention of upper gastrointestinal bleeding in NSAID u sers. Methods: NSAID users presenting with upper gastrointestinal bleeding were e nrolled if they required long-term NSAIDs. After ulcer healing, they were r andomized to receive: naproxen (500-1000 mg/day) and misoprostol (200 mug 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 gas trointestinal events including ulcer bleeding, symptomatic ulcers and sever e dyspepsia. Results: A total of 90 patients were included in the intention-to-treat ana lysis (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=0.06 9). 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 n abumetone group. Conclusions: Misoprostol/naproxen is not superior to nabumetone for seconda ry prevention of upper gastrointestinal bleeding. Neither low-dose misopros tol nor nabumetone is adequate for high-risk NSAID users.