Alternate Sites Forum

NSAIDs: Articles Review Problems, Solutions

The use of nonsteroidal anti-inflammatory agents-also covered in this month's "Consultants Forum"-can be problematic in the ambulatory population seen in home care and assisted living facilities. Four recently published articles offer insights into the gastrointestinal havoc created by NSAIDs-as well as analyses of possible pharmacotherapeutic solutions.

The adverse outcomes associated with NSAID use are presented in Postgraduate Medicine.¹ Pearson and Kelberman note that patients must be "vigilantly monitored for signs and symptoms of reactions to the drugs." When discontinuance is not an option, omeprazole is the only agent that can speed healing, the authors note. They recommend misoprostol as prophylaxis in patients at highest risk who must receive NSAIDs-a recommendation that matches the advice Higa offers in the "Consultants Forum" article in this issue of TCP.² (Reprints: S. P. Pearson, School of Medicine, Temple University, 3401 N. Broad St., 757 Parkinson Pavilion, Philadelphia, PA 19140.)

Two recent papers on the use of NSAIDs are based on data obtained from prescriptions filled in Saskatch-ewan in 1982-86.^3,4 Among people not exposed to NSAIDs, the incidence of hospitalization for acute renal failure was two per 100,000 person-years. Current NSAID users had an adjusted odds ratio of 4.1, and the risk of acute renal failure was especially high in the first month of therapy. The risks from concomitant use of other nephrotoxic drugs was substantially greater than the sum of the individual risks.³ The second report relies on the same database of prescription files. It concludes: "Simultaneous use of multiple NSAIDs as well as use of a single individual NSAID at high doses greatly increases the risk of complicated peptic ulcer disease." The adjusted odds ratio for current NSAID use was 4.3 for upper gastrointestinal bleeding or perforation, and odds ratios for current NSAID use were similar for fatal cases and for gastric, duodenal, prepyloric, and multiple sites of lesions. The odds ratio was similar for perforations.⁴ (Reprints: S. P. Gutthann, Pharmacoepidemiology Research, FM 2.6, Ciba-Geigy SA, C. de la Marina 206, 08013 Barcelona, Spain.)

Koch et al.⁵ present in Archives of Internal Medicine a meta-analysis of 24 studies on prevention of NSAID-induced gastrointestinal injury. Included in the analysis were placebo-controlled, randomized trials published between January 1970 and December 1994 that used H₂ blockers and/or misoprostol. Three independent observers systematically assessed the results, comparing crude rates of endoscopically proven lesions with short-term versus long-term NSAID exposure. The authors found histamine H₂ antagonists to be of no proven benefit in prevention of gastric ulcers, while misoprostol produced significant protection both in short-term and long-term treatments with NSAIDs. At an intermediate baseline risk of 10%, the authors found that, for short- and long-term prevention, 11 and 15 patients, respectively, would have to be treated so that one gastric ulcer could be prevented. For duodenal ulcers, misoprostol and H₂ blockers produced significant protection in long-term but not short-term trials. The group could recommend no agent for duodenal ulcer prevention based on this meta-analysis. (Reprints: M. Koch, Dept. of Digestive Diseases and Nutrition, General Hospital San Filippo Neri, Via Martinotti 20, 00135 Rome, Italy.)

L. Michael Posey, Academics Editor

References

1. Pearson SP, Kelberman I. Gastrointestinal effects of NSAIDs. Postgrad Med 1996; 100(5):131-43.

2. Higa JH. Interventions in nursing home residents receiving NSAIDs: preventing GI damage and complications. Consult Pharm 1997; 12: 304-6.

3. Gutthann SP, Rodriguez LAG, Raiford DS, Oliart AD, Romeu JR. Nonsteroidal anti-inflammatory drugs and the risk of hospitalization for acute renal failure. Arch Intern Med 1996; 156:2433-9.

4. Gutthann SP, Rodriguez LAG, Raiford DS. Individual nonsteroidal antiinflammatory drugs and other risk factors for upper gastrointestinal bleeding and perforation. Epidemiology 1997; 8:18-24.

5. Koch M, Dezi A, Ferrario F, Capurso L. Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. Arch Intern Med 1996; 156:2321-32.