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Eibert R. Heerdink, PhD; Hubert G. Leufkens, PhD; Ron M. C. Herings, PhD; Jan P. Ottervanger, MD; Bruno H. C. Stricker, MD; Albert Bakker, PhD

Arch Intern Med. 1998;158:1108-1112.

Background  Both diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, in particular among the elderly. The use of NSAIDs may decrease the efficacy of diuretics and induce congestive heart failure (CHF) in patients treated with diuretics.

Objective  To investigate the risk of CHF associated with combined use of diuretics and NSAIDs in patients older than 55 years.

Methods  We conducted a study in a base cohort of 10519 recipients of diuretics and NSAIDs identified in the PHARMO database during the period from 1986 through 1992. The incidence density of hospitalizations for CHF during exposure to both diuretics and NSAIDs (index) was compared with that during exposure to diuretics only (reference).

Results  We found an overall increased risk of hospitalization for CHF during periods of concomitant use of diuretics and NSAIDs compared with use of diuretics only (crude relative risk, 2.2; 95% confidence interval, 1.7-2.9). After adjusting for cofactors including age, sex, history of hospitalization, and drug use, a 2-fold increased risk remained (relative risk, 1.8; 95% confidence interval, 1.4-2.4).

Conclusion  Use of NSAIDs in elderly patients taking diuretics is associated with a 2-fold increased risk of hospitalization for CHF, especially in those with existing serious CHF.

From the Department of Pharmacoepidemiology and Pharmacotherapy, University of Utrecht, Utrecht, the Netherlands (Drs Heerdink, Leufkens, Herings, and Bakker); Department of Epidemiology and Biostatistics, Erasmus University, Rotterdam, the Netherlands (Drs Ottervanger and Stricker); and Department of Cardiology, Hospital "De Weezenlanden," Zwolle, the Netherlands (Dr Ottervanger).

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