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Use of Diuretics and the Risk of Gouty Arthritis: A Systematic Review

  • Berdine A.A. Hueskes, BSc

      Affiliations

    • Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands
    • Department of Rheumatology, Rijnstate, Arnhem, The Netherlands
  • ,
  • Elisabeth A. Roovers, PhD

      Affiliations

    • Department of Clinical Research, Rijnstate, Arnhem, The Netherlands
  • ,
  • Aukje K. Mantel-Teeuwisse, PhD

      Affiliations

    • Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands
  • ,
  • Hein J.E.M. Janssens, PhD

      Affiliations

    • Department of Primary and Community Care, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands
    • Primary Care Health Centre Lobede, Lobith-Tolkamer, The Netherlands
  • ,
  • Eloy H. van de Lisdonk, PhD

      Affiliations

    • Department of Primary and Community Care, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands
  • ,
  • Matthijs Janssen, PhD

      Affiliations

    • Department of Rheumatology, Rijnstate, Arnhem, The Netherlands
    • Corresponding Author InformationAddress reprint requests to Matthijs Janssen, PhD, PO Box 9555, Postnr 1230, 6800 TA Arnhem, The Netherlands

published online 06 January 2012.
Corrected Proof

Objective

To systematically review the literature investigating the relationship between use of diuretics and the risk of gouty arthritis.

Methods

PubMed (1950-October 2009), Embase (1974-October 2009), and the Cochrane Library (up to October 2009) were searched using keywords and MeSH terms diuretics, adverse effects, and gout. For this review, the technique of “best evidence synthesis” was used. Studies reporting frequency, absolute or relative risks, odds ratio, or rate ratio of gouty arthritis in diuretic users compared with nonusers were selected and evaluated. Studies had to be published in English. Checklists from the Dutch Cochrane Centre were used to assess the quality of randomized controlled trials (RCTs), cohort, and case-control studies.

Results

Two RCTs, 6 cohort studies, and 5 case-control studies met the inclusion criteria. The overall quality of the studies was moderate. In a RCT the rate ratio of gout for use of bendrofluazide vs placebo was 11.8 (95% CI 5.2-27.0). The other RCT found a rate ratio of 6.3 (95% CI 0.8-51) for use of hydrochlorothiazide plus triamterene vs placebo. Three cohort studies and 4 case-control studies found higher risks of gouty arthritis in users compared with nonusers of diuretics.

Conclusions

There is a trend toward a higher risk for acute gouty arthritis attacks in patients on loop and thiazide diuretics, but the magnitude and independence is not consistent. Therefore, stopping these useful drugs in patients who develop gouty arthritis is not supported by the results of this review.

Keywords:  diuretics , gouty arthritis , hyperuricemia , systematic review

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 No direct funding has been received for this study. The division of Pharmacoepidemiology and Clinical Pharmacology employing AKM-T has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, the private-public funded Top Institute Pharma (www.tipharma.nl, includes cofunding from universities, government, and industry), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health. All other authors declare that they have no conflicts of interest to disclose.

PII: S0049-0172(11)00358-1

doi:10.1016/j.semarthrit.2011.11.008

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