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Canadian Journal of Cardiology

Hypouricemic Effects of Prednisone and Allopurinol: An Uneven Playing Field?

      To the Editor:
      We read with interest the article of Liu et al. on the urate-lowering effect of prednisone in patients with symptomatic heart failure.
      • Liu C.
      • Zhao Q.
      • Zhen Y.
      • et al.
      Prednisone in uric acid lowering in symptomatic heart failure patients with hyperuricemia (PUSH-PATH) study.
      We were interested in the potential use of prednisone to lower plasma urate levels but were surprised that prednisone (1 mg/kg/d, max 60 mg/d) had a urate-lowering capacity similar to that of allopurinol (300 mg/d), the most commonly used treatment for gout.
      • Annemans L.
      • Spaepen E.
      • Gaskin M.
      • et al.
      Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000-2005.
      We hypothesize that the data were skewed in favour of the prednisone treatment showing a similar urate-lowering effect because of the differences in the dose of concomitant furosemide administration. Although both groups had roughly equal doses of furosemide at baseline (65 ± 34 mg/d and 62 ± 30 mg/d, prednisone and allopurinol groups, respectively), the dose of furosemide was approximately halved (32 ± 25 mg/d) at week 4 in the prednisone group (P < 0.001). By contrast, the dosage of furosemide in the group treated with allopurinol remained unchanged (60 ± 28 mg/d).
      A dose-response relationship between furosemide and plasma urate levels has been documented, showing that increasing doses of furosemide are associated with increasing plasma urate concentrations.
      • Ramsay L.E.
      • McInnes G.T.
      • Hettiarachchi J.
      • Shelton J.
      • Scott P.
      Bumetanide and frusemide: a comparison of dose-response curves in healthy men.
      Hence, we conclude that the net reduction in plasma urate levels in the prednisone group (321 ± 123 μmol/L) is attributable in part to the reduction in the furosemide dose in this group.
      Although the authors have acknowledged that their study was underpowered, we suggest that any larger study should control the dose of furosemide to better understand the absolute effect of prednisone alone.

      Disclosures

      The authors have no conflicts of interest to disclose.

      References

        • Liu C.
        • Zhao Q.
        • Zhen Y.
        • et al.
        Prednisone in uric acid lowering in symptomatic heart failure patients with hyperuricemia (PUSH-PATH) study.
        Can J Cardiol. 2013; 29: 1048-1054
        • Annemans L.
        • Spaepen E.
        • Gaskin M.
        • et al.
        Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000-2005.
        Ann Rheum Dis. 2008; 67: 960-966
        • Ramsay L.E.
        • McInnes G.T.
        • Hettiarachchi J.
        • Shelton J.
        • Scott P.
        Bumetanide and frusemide: a comparison of dose-response curves in healthy men.
        Br J Clin Pharmacol. 1978; 5: 243-247

      Linked Article

      • Prednisone in Uric Acid Lowering in Symptomatic Heart Failure Patients With Hyperuricemia (PUSH-PATH) Study
        Canadian Journal of CardiologyVol. 29Issue 9
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          Chronic drug interactions that exist between symptomatic congestive heart failure (CHF) therapy and pharmacologic agents used for hyperuricemia and gout are a challenging problem in clinical practice. Recent observational studies showed that prednisone can induce a potent diuresis and lower serum uric acid concentration (SUA) in CHF. We therefore designed a randomized study to compare the effect of prednisone with allopurinol on SUA in symptomatic CHF patients with hyperuricemia.
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      • Reply to Day et al.—Hypouricemic Effect of Prednisone in Heart Failure: Possible Mechanisms
        Canadian Journal of CardiologyVol. 30Issue 3
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          We thank Dr Day and colleagues for raising the issue about the relationship between uric acid (UA) levels and furosemide dosages in our study. Many observational studies have shown higher furosemide doses are associated with worsening renal function and decreased UA excretion. However, these observations are all confounded by the fact that patients with heart failure receiving higher doses of diuretics do so owing to greater disease severity or worse renal function. This is the case with our study in which the clinical characteristics and the doses of furosemide are well matched at baseline.
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