Eradication of Helicobacter pylori before NSAID treatment prevented ulcers
ACP J Club. 1998 Mar-April; 128:44. doi:10.7326/ACPJC-1998-128-2-044
Chan FK, Sung JJ, Chung SC, et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet. 1997 Oct 4;350:975-9.
To determine whether eradication of Helicobacter pylori before treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is started will prevent development of NSAID-induced peptic ulcers.
Randomized controlled trial.
2 outpatient clinics in Hong Kong.
202 adults with musculoskeletal disorders who needed NSAIDs were evaluated. Exclusion criteria were age < 18 years; previous exposure to NSAIDs, including aspirin, for > 1 month; use of NSAIDs, antiulcer drugs, steroids, anticoagulants, or cytotoxic agents in the previous 8 weeks; receipt of anti- Helicobacter therapy; history of peptic ulcer disease or gastric surgery; or renal impairment. 100 patients had confirmed H. pylori infection and entered the study; 92 completed it (median age > 60 y, 72% men).
50 patients were allocated to triple therapy (bismuth subcitrate, 120 mg; tetracycline, 500 mg; and metronidazole, 400 mg each given 4 times/d) for a week before receiving naproxen, 250 mg 3 times/d for 8 weeks. 50 patients were allocated to naproxen alone for 8 weeks.
Main outcome measures
Cumulative rate of endoscopy-proven gastric and duodenal ulcers ≥ 5 mm in diameter. Helicobacter pylori status was reconfirmed on follow-up endoscopy.
At the end of the study, all patients in the naproxen-alone group and 11% of patients in the triple therapy group had confirmed H. pylori infection. Intention-to-treat analysis showed that patients who received pretreatment with triple therapy to eradicate H. pylori infection had fewer total ulcers than patients who received no pretreatment (P = 0.01) (Table). Per-protocol analysis showed similar results for total ulcers (P = 0.007). Neither analysis showed differences between the groups for symptomatic ulcers (P = 0.1 for both).
Eradication of Helicobacter pylori infection before starting treatment with naproxen, a nonsteroidal anti-inflammatory drug, reduced the development of drug-induced ulcers.
Source of funding: No pharmaceutical company funding.
For article reprint: Dr. F.K. Chan, Department of Medicine, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. FAX 852-2637-3852.
Table. Total ulcers with triple therapy plus naproxen vs naproxen alone*
|Type of analysis||Triple therapy EER||Naproxen alone CER||RRR (95% CI)||ARR |EER-CER|||NNT (CI)|
|ITT||7%||26%||74% (21 to 92)||19%||6 (3 to 24)|
|Per-protocol||5%||28%||81% (32 to 95)||23%||5 (3 to 14)|
*ITT = intention-to-treat. Other abbreviations defined in Glossary; RRR, ARR, NNT, and CI calculated from data in article.
Whether H. pylori infection increases the risk for NSAID-induced ulcers and ulcer complications is highly controversial because cross-sectional and cohort studies have had conflicting results (1, 2). Chan and colleagues report the first randomized trial to investigate whether eradication of H. pylori with triple therapy before instituting NSAID therapy reduces the subsequent risk for chronic ulcers. The results convincingly show that curing the infection is protective.
Clinicians should note that 1 patient (2.5%) who had successful eradication of H. pylori still developed an ulcer, whereas 12 (26%) patients who remained infected developed ulcers. The rate of symptomatic ulcers was not increased in patients who were infected, but this may be explained by the relatively small sample size.
The results of this trial may not apply to patients who take NSAIDs for long periods or those who have used NSAIDs in the past, because these patients were not evaluated. The results also need to be confirmed by trials using non-bismuth-based triple therapies because bismuth may have cytoprotective effects. Presumably, cure of H. pylori infection will reduce long-term ulcer complications in patients who use NSAIDs, but this has not been established.
Co-prescription of potent acid suppressors (3) or misoprostol (4) or cure of H. pylori infection provides similar degrees of protection from ulcer development in persons who use NSAIDs, at least in the short term.
Before changes in management can be widely recommended for patients starting NSAID therapy, however, it will need to be shown that over the long term it is cost-effective to screen and treat persons with H. pylori infection.
Nicholas J. Talley, MD, PhD
Guy D. Eslick, BAppSc, Grad Dip Epi (Clin Epi)University of SydneySydney, New South Wales, Australia
1. Loeb DS, Talley NJ, Ahlquist DA, Carpenter HA, Zinsmeister AR. Long-term nonsteroidal anti-inflammatory drug use and gastroduodenal injury: the role of Helicobacter pylori. Gastroenterology. 1992;102:1899-905.
4. Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial.Ann Intern Med. 1995;123:241-9.