Doctors Beware: Certain Antihypertensives Can Increase the Risk of Gout

February 16, 2012
Gregory W. Rutecki, MD

Unfortunately, the growing epidemics of hypertension and gout are often a package deal. Recent data demonstrate that 74% of people with gout are also hypertensive.

Unfortunately, the growing epidemics of hypertension and gout are often a package deal. Recent data demonstrate that 74% of people with gout are also hypertensive.1

One caveat has stood for years, but has not been cortically revisited. When prescribing antihypertensives for persons with gout, avoid diuretics. The volume-contracting effects of diuretics increase serum uric acid levels and may precipitate gout.

But there may be more to this hypertension treatment–gout story.

Investigators decided that it was time to reevaluate the question by looking at a host of antihypertensives used with and without diuretics.1 They investigated 24,768 people with newly diagnosed gout who required antihypertensive therapy vis-à-vis 50,000 matched controls.

Appropriate adjustments were made for age, sex, body mass index, doctor visits, alcohol ingestion, comorbidities, and other drugs prescribed. Gout was proved by an index date of occurrence, as well as use of anti-gout medications (colchicine, probenecid, or NSAIDs). Some doctor subjectivity was allowed in the diagnosis of gout. Because previous studies suggested that losartan, unlike other angiotensin II receptor blockers (ARBs), lowers urate levels, this drug was studied separately from other members of its antihypertensive class.

Antihypertensives from various groupings had differing effects on gouty occurrences. The relative risk of gout for all these agents were:
• 0.87 for calcium channel blockers (dihydropyridine versus others was not significantly different)
• 0.81 for losartan
• 2.36 for diuretics
• 1.48 for beta-blockers
• 1.24 for ACE inhibitors
• 1.29 for non-losartan ARBs.

Associations between antihypertensives and gout were stronger with longer durations of use and higher dosages of the antihypertensive agent in question. If dual therapy was prescribed for hypertension (for instance, diuretics plus ACE inhibitors or diuretics plus beta-blockers), risks increased (3.17 and 3.33, respectively) with 2-drug therapy compared with no antihypertensive therapy. Again, calcium channel blockers with a diuretic somewhat lessened the risk of gout (2.11) compared with a diuretic given with the previously mentioned agents.

What are the messages that can inform primary care? Calcium channel blockers, non-dihydropyridine and dihydropyridine varieties, lower uric acid levels. The effect may be contingent on vasodilatation and on increases in glomerular filtration rate. Decreased proximal tubular absorption of uric acid may also play a role.

Another large trial has demonstrated that nifedipine reduces serum uric acid levels in patients with coronary disease.2 The urate-lowering effects of losartan, especially compared with other ARBs, are a result of a uricosuric effect not shared by other drugs in this class.

The bottom line
When possible, prescribe losartan and/or calcium channel blockers as hypertensive therapy in people with gout or in whom gout develops during antihypertensive drug treatment. With the rising number of resistant hypertensive patients (ie, individuals who require 3 or more medications to control blood pressure), this approach will not always be possible. Despite the helpful data in this study, specific treatment for recurrent gout will still be required.  
1. Choi HK, Soriano LC, Zhang Y, Garcia Rodriguez LA. Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ. 2012;344:d8190. doi:10.1136/bmj.d8190.

2. Ruilope LM, Kirwan BA, de Brouwer S, et al. Uric acid and other renal function parameters in patients with stable angina pectoris participating in the ACTION Trial: impact of nifedipine GITS and relation to outcome. J Hypertens. 2007;25:1711-1718.