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Douglas J. Watson, PhD; Thomas Rhodes, MS; Bing Cai, MS; Harry A. Guess, MD, PhD

Arch Intern Med. 2002;162:1105-1110.

Background  Naproxen strongly inhibits platelet aggregation.

Objective  To examine the risk of acute thromboembolic cardiovascular events (TCEs) (myocardial infarction, sudden death, and stroke) with current naproxen use among patients with rheumatoid arthritis.

Methods  We studied patients aged 40 to 79 years with rheumatoid arthritis in the British General Practice Research Database, excluding those with a prior TCE and potentially confounding conditions. We matched up to 4 controls by sex, age, and site of medical practice to cases with first incident TCEs. The case diagnosis date was designated as the index date for each case and his or her controls. We categorized naproxen according to the most recent prescription prior to the index date as being current (30 days), past (>30 days but <365 days), or none (365 days before index date). Using conditional logistic regression, we conducted a matched case-control analysis with adjustment for potential confounders.

Results  We identified 809 cases. Current naproxen use was more common among controls (5.7%) than cases (3.2%). Adjusting for calendar year of treatment start, systemic corticosteroid use, diabetes, and comorbidity, we found that the odds ratio (95% confidence interval) for current naproxen use was 0.61 (0.39-0.94) while that for past use was 0.87 (0.65-1.16). Secondary and sensitivity analyses supported these results.

Conclusions  In this case-control study, patients with rheumatoid arthritis and a current prescription for naproxen had a reduced risk of acute major TCEs relative to those with no naproxen prescription in the past year. These results are consistent with the ability of naproxen to inhibit platelet aggregation.

From Merck Research Laboratories, Blue Bell, Pa. All authors are employees of Merck & Co Inc and may own stock in the company.

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