Thiazide diuretics and anti-gout therapy

Clinical bottom line

Thiazide diuretics double the risk of being put on anti-gout therapy, to the extent of about 1% of persons treated with thiazides.

Reference

JH Gurwitz et al. Thiazide diuretics and the initiation of anti-gout therapy. J Clin Epidemiol 1997 50: 953-957.

Study

The study population was the New Jersey Medicaid programme for 1981 to 1989, which has data on medication use and filled prescriptions. Participants were aged 65 or older filling a first prescription for antihypertensive medicine, with no prior use of anti-gout medicine (allopurinol, colchicine or a uricosuric agent). Follow up was for a minimum of one year and maximum of two years after the first antihypertensive prescription. There were 9,249 persons who met these requirements.

Anti-gout therapies examined included oral colchicine, allopurinol, probenecid and sulfinpyrazone, but not NSAIDs or glucocorticoids because they are not specific to the treatment of gout.

Results

The study population was predominantly female (77%), white (69%) and over 75 years old (55%). There were 168 patients who started anti-gout therapy during follow up, mostly for allopurinol (84%) and colchicine (9%). Exposure to thiazide diuretics, alone or in combination, produced higher rates of anti-gout therapy (Table 1).

Table 1: anti-gout therapy and antihypertensive exposure

Exposure to antihypertensive	Events	Person years	Rate per 1000 person years (95% CI)
No exposure	81	8927	9.1 (7.1 to 11.1)
Non-thiazide alone	28	3952	7.1 (4.5 to 9.7)
Thiazide alone	22	1521	14.5 (8.4 to 20.5)
Combination	37	2641	14.0 (9.5 to 18.5)

Anti-gout therapy was mostly begun after the first 90 days of exposure, with only 21/168 occurring within the first 90 days. The relative risk (compared to no exposure was 1.0 (0.7 to 1.5) for non-thiazide antihypertensives, 2.0 (1.2 to 3.3) for thiazide alone, and 2.3 (1.6 to 3.4) for combinations.

Dose of thiazide was important. When the dose was less than 25 mg hydrochlorothioazide-equivalent milligrams a day the increase was non-significant, but was significant for doses higher than this (Figure 1). Half the doses were for more 50 mg a day or more, 38% for 25-49 mg and 11% were for less than 25 mg a day hydrochlorothioazide-equivalent milligrams.

Figure 1: Anti-gout therapy according to hydrochlorothioazide-equivalent milligrams a day

Comment

That there is an association between thiazide diuretics and hyperuricaemia and gout is well known, but no previous study has examined the size of the association. There is a substantially increased risk of having anti-gout therapy initiated when thiazide diuretics are used, but the absolute risk is small (about 1%) in a population in which we have no idea about the initial uric acid level.

What is good about the study is that it is large and comprehensive for an entire population. Most of the people in it were women: there was no sub-group analysis by gender. It was not possible to assess whether use of allopurinol was associated with treating gout, or prophylactic treatment of asymptomatic hyperuricaemia.