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

https://doi.org/10.1016/j.semarthrit.2011.11.008Get rights and content

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.

Section snippets

Data Sources

PubMed (1950-October 2009), Embase (1974-October 2009), and the Cochrane Library (up to October 2009) were searched, with keywords/MeSH terms “gout and diuretics” and “diuretics and adverse effects”. In addition, reference lists of retrieved studies were checked for other relevant citations.

Study Selection and Data Extraction

For this review we used the technique of “best evidence synthesis” (28). We used the following a priori inclusion criteria: studies reporting the frequency, absolute or relative risks, odds ratio, or rate

Results

The PubMed search yielded 336 hits; the Embase search yielded 733 hits, and the Cochrane Library found 14 clinical trials concerning the combination “gout and diuretics”. The PubMed search with MeSH terms “diuretics and adverse effects” resulted in 3117 hits. The process of literature search and selection is depicted in Figure 1. Two RCTs (34, 35), 6 cohort studies (30, 37, 38, 39, 40, 41), and 5 case-control studies (42, 43, 44, 45, 46) met the selection criteria and were evaluated for quality

Discussion

The results of this literature review indicate that the risk of gouty arthritis is increased in patients who use diuretics. This is in line with current guidelines and the point of view that gouty arthritis is a side effect of diuretic use. However, there is still no conclusive evidence about an independent inducing effect of diuretics on the development of gouty arthritis. Considering the various quality aspects, the composite percentage of quality of the selected studies was moderate. In

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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.

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