It’s okay in most cases for gout patients to be on thiazide diuretics or low-dose aspirin, so long as hypouricemic therapy is adjusted as needed, according to rheumatologist and Cleveland Clinic professor Dr. Brian F. Mandell.
Coronary artery disease is common in gout, so patients benefit from inexpensive, well-tolerated, and effective treatments like thiazides for hypertension and 81 mg aspirin daily for cardioprotection, Dr. Mandell said at the annual Perspectives in Rheumatic Diseases conference held by Global Academy for Medical Education.
Dr. Brian F. Mandell
The concern, however, is that both can elevate serum uric acid. Observational and survey data suggest that the drugs may be associated with an increase in attacks, so some shy away from them in gout.
To make sense of the issue, the first thing to remember is that the drugs cause only “minimal elevations in serum uric acid. Serum urate can still be lowered to less than 6 mg/dL with appropriate therapy without stopping them,” Dr. Mandell said.
Low-dose aspirin raises serum urate by about 0.3 mg/dL. At 12.5 or 25 mg once a day – common hypertension doses – hydrochlorothiazide increases serum urate by 0.8 mg/dL or less in patients with normal renal function (Arthritis Rheum. 2012 Jan;64[1]:121-9).
“In patients with chronic gout treated with a xanthine oxidase inhibitor (allopurinol or febuxostat) to lower the serum urate” to recommended target levels below 6.0 mg/dL, “the small elevation in serum urate is unlikely to negate the clinical efficacy of these drugs when dosing is optimized,” Dr. Mandell wrote in an article that expands upon his presentation points (Cleve Clin J Med. 2014 Feb;81[2]:83-6).
Based on those considerations, “my practice in most patients is to use a thiazide if it helps to control the blood pressure and to adjust the dose of the hypouricemic therapy as needed to reduce the serum urate to the desired level. ... Continuing thiazide therapy and, if necessary, adjusting hypouricemic therapy will not worsen the control of the serum urate level or gouty arthritis, and in most patients will not complicate the management of gout.” In general, “when I add a thiazide to a patient’s regimen, I do not usually need to increase the dose of allopurinol significantly to keep the serum urate level below the desired target,” he said.
The approach is similar with low-dose aspirin. Because of its negligible effect on serum uric acid levels, it does not need to be stopped in hyperuricemia or gout. “Since patients with gout have a higher risk of having cardiovascular disease, metabolic syndrome, and chronic kidney disease, many will benefit from low-dose aspirin therapy,” he said.
Occasionally, it makes sense to switch from a thiazide to another hypertensive, such as losartan, in chronic, hypertensive gout patients with serum urate levels marginally above the precipitation threshold of 6.7 mg/dL. “Losartan is a weak uricosuric and can lower the serum urate level slightly, possibly making the addition of another hypouricemic agent unnecessary, while still controlling the blood pressure with a single pill,” Dr. Mandell said.
The decision “must be individualized, taking into consideration the efficacy and cost of the alternative antihypertensive drug, as well as the potential but as yet unproven cardiovascular and renal benefits of lowering the serum urate with a more potent hypouricemic to a degree not likely to be attained with losartan alone,” he said.
Dr. Mandell has been a consultant for Savient/Crealta, AstraZeneca, Regeneron, and Novartis. Global Academy for Medical Education and this news organization are owned by the same parent company.