sign in sign up
<<
Home , Gout

1-MINUTE CONSULT

BRIEF ANSWERS TO SPECIFIC CLINICAL Q: Should patients with gout avoid QUESTIONS for ?

BRIAN F. MANDELL, MD, PhD Professor and Chairman, Department of Academic Medicine; Department Drugs mentioned in this article of Rheumatic and Immunologic Diseases, Cleveland Clinic; Editor in Chief, Cleveland Clinic Journal of Medicine (Zyloprim) The decision should be individual- A: ized, taking into consideration the chlorthalidone (Thalitone) degree to which the increases the (Uloric) serum urate level, whether this increase can be managed without overly complicating the patient’s hypouricemic therapy, and, most im- (Cozaar) portantly, what effect switching to another drug will have on the control of the patient’s pressures are complex and many: physicians hypertension. No study has directly addressed may simply not be aggressive enough in pur- this issue. suing a target blood pressure; patients cannot My practice in most patients, for reasons I tolerate the drugs or cannot afford the drugs; explain below, is to use a thiazide if it helps to and many patients need two or more antihy- In most cases, control the blood pressure and to adjust the pertensive drugs to achieve adequate control. I continue dose of the hypouricemic therapy as needed to Thiazides are cheap and effective5 and work reduce the serum urate to the desired level. synergistically with angiotensin-converting the thiazide enzyme inhibitors and angiotensin receptor and adjust the 6 ■■ THIAZIDES REMAIN IMPORTANT blockers. hypouricemic IN ANTIHYPERTENSIVE THERAPY Thus, in many patients, avoiding or dis- continuing a thiazide may inhibit our abil- therapy if Many patients with gout also have hyperten- ity to control their hypertension, which is necessary sion, perhaps due in part to the same hyper- a key contributor to cardiovascular events uricemia that caused their gouty . It is and chronic in patients with to reach well documented that thiazide can gout. Since other diuretics (eg, loop diuret- the target raise the serum urate level.1 In some studies2 ics, which can lower blood pressure but often (but not all3), patients using thiazides had a require split doses) also raise the serum urate serum higher incidence of gouty arthritis. Thus, it is level, switching to one of them will not elimi- level reasonable to ask if we should avoid thiazides nate concern over . in patients with coexistent gout and hyperten- sion. Thiazides and serum urate Many hypertensive patients fail to reach Thiazides slightly increase the serum urate their target blood pressures (although with level and in a dose-dependent manner. At the “looser” recommendations in the latest the doses commonly used in treating hyper- guidelines,4 we may appear to be doing a bet- tension (12.5 or 25 mg once a day), hydro- ter job). The reasons for failing to reach target chlorothiazide increases the serum urate level by 0.8 mg/dL or less in patients with normal doi:10.3949/ccjm.81a.13131 renal function, as shown in a number of older

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 81 • NUMBER 2 FEBRUARY 2014 83 Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. GOUT

hypertension treatment trials and in a recent a single pill. This decision must be individu- prospective study.1 The effect of chlorthali- alized, taking into consideration the efficacy done is similar. and cost of the alternative antihypertensive In patients with chronic gout treated with drug, as well as the potential but as yet un- a inhibitor (allopurinol or proven cardiovascular and renal benefits of febuxostat) to lower the serum urate to the lowering the serum urate with a more potent American College of ’s recom- hypouricemic to a degree not likely to be at- mended target level7 of less than 6.0 mg/dL (or tained with losartan alone. < 5 mg/dL in the British Rheumatology guide- lines), this small elevation in serum urate is Continue thiazide, adjust gout therapy unlikely to negate the clinical efficacy of these Discontinuing a thiazide or switching to an- drugs when dosing is optimized. Small stud- other may increase the ies have demonstrated a clinically insignifi- cost and decrease the efficacy of hypertensive cant pharmacodynamic interaction between therapy. Continuing thiazide therapy and, thiazides and xanthine oxidase inhibitors.8,9 if necessary, adjusting hypouricemic therapy When I add a thiazide to a patient’s regimen, I will not worsen the control of the serum urate do not usually need to increase the dose of al- level or gouty arthritis, and in most patients lopurinol significantly to keep the serum urate will not complicate the management of gout. level below the desired target. ■■ ASPIRIN AND HYPERURICEMIA Switch antihypertensive therapy Occasionally, in a patient with chronic gout In answer to a separate but related question, as- and mild hypertension who has a serum urate pirin in low doses for cardioprotection (81 mg level marginally above the estimated precipi- daily) also need not be stopped in patients with tation threshold of 6.7 mg/dL, it is reasonable hyperuricemia or gout in an effort to better to simply switch the thiazide to another an- control the serum urate level. Low-dose aspi- tihypertensive, such as losartan. Losartan is a rin increases the serum urate level by about 0.3 Hydrochloro- weak and can lower the serum urate mg/dL. Since patients with gout have a higher thiazide level slightly, possibly making the addition risk of having , metabolic of another hypouricemic agent unnecessary, syndrome, and chronic kidney disease, many 12–25 mg while still controlling the blood pressure with will benefit from low-dose aspirin therapy. ■ daily increases ■■ REFERENCES 6. Sood N, Reinhart KM, Baker WL. Combination therapy the serum for the management of hypertension: a review of the 1. McAdams DeMarco MA, Maynard JW, Baer AN, et al. evidence. Am J Health Syst Pharm 2010; 67:885–894. urate level use, increased serum urate levels, and risk of 7. Khanna D, Fitzgerald JD, Khanna PP, et al; American incident gout in a population-based study of adults with College of Rheumatology. 2012 American College of by ≤ 0.8 mg/dL hypertension: the Atherosclerosis Risk in Communities Rheumatology guidelines for management of gout. cohort study. Arthritis Rheum 2012; 64:121–129. Part 1: systematic nonpharmacologic and pharmacologic 2. Choi HK, Soriano LC, Zhang Y, Rodríguez LA. Antihyper- therapeutic approaches to hyperuricemia. Arthritis Care tensive drugs and risk of incident gout among patients Res (Hoboken) 2012; 64:1431–1446. with hypertension: population based case-control study. 8. Löffler W, Landthaler R, de Vries JX, et al. Interac- BMJ 2012; 344:d8190. tion of allopurinol and hydrochlorothiazide during 3. Hueskes BA, Roovers EA, Mantel-Teeuwisse AK, Janssens prolonged oral administration of both drugs in nor- HJ, van de Lisdonk EH, Janssen M. Use of diuretics and mal subjects. I. Uric acid kinetics. Clin Investig 1994; the risk of gouty arthritis: a systematic review. Semin 72:1071–1075. Arthritis Rheum 2012; 41:879–889. 9. Grabowski B, Khosravan R, Wu JT, Vernillet L, 4. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based Lademacher C. Effect of hydrochlorothiazide on the guideline for the management of high blood pressure in pharmacokinetics and pharmacodynamics of febuxostat, adults. Report from the panel members appointed to the a non- selective inhibitor of xanthine oxidase. Br J Eighth National Committee (JNC 8). JAMA 2013; Clin Pharmacol 2010; 70:57–64. doi:10.1001/jama 2013.284427 5. Fuchs FD. Diuretics: still essential drugs for the manage- ADDRESS: Brian F. Mandell, MD, PhD, Internal Medicine Resi- ment of hypertension. Expert Rev Cardiovasc Ther 2009; dency Program, NA1-10, Cleveland Clinic, 9500 Euclid Avenue, 7:591–598. Cleveland, OH 44195; e-mail: [email protected]

86 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 81 • NUMBER 2 FEBRUARY 2014 Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission.