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 to 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, gender, body mass index, doctor visits, alcohol(Drug information on alcohol) ingestion, comorbidities, and other drugs prescribed. Gout was proven by an index date of occurrence, as well as use of anti-gout medications (colchicine, probenecid(Drug information on probenecid), or NSAIDs). Some doctor subjectivity was allowed in the diagnosis of gout. Because previous studies suggested that losartan(Drug information on losartan), unlike other angiotension 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 ACEIs or diuretics plus beta-blockers), risks increased (3.17 and 3.33 respectively) with 2 drug therapy when compared with patients not taking antihypertensives. Again, calcium channel blockers with a diuretic somewhat lessened the risk of gout (2.11) compared with a diuretic given with the previous agents.
What are the messages that can inform primary care? Calcium channel blockers, non- and dihydropyridine varieties, lower uric acid. The effect may be contingent on vasodilatation and on increases in GFR. Decreased proximal tubular absorption of uric acid may also play a role.
Another large trial has demonstrated that nifedipine(Drug information on nifedipine) reduces serum uric acid in patients with coronary disease.2 The urate lowering effects of losartan, especially compared to 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 hypertensives (ie, individuals who require 3 or more medicines 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.
References:
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.
