Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study

Abstract

Objective: To examine whether allopurinol is associated with any alteration in mortality and hospitalisations in patients with chronic heart failure (CHF). This hypothesis is based on previous data that a high urate concentration is independently associated with mortality with a risk ratio of 4.23 in CHF. Design: Retrospective cohort study. Setting: Medicines Monitoring Unit, Ninewells Hospital, Dundee, UK. Patients: 1760 CHF patients divided into four groups: those on no allopurinol, those on long term low dose allopurinol, those on short term low dose allopurinol, and those on long term high dose allopurinol. Main outcome measures: Total mortality, cardiovascular mortality, cardiovascular hospitalisations, cardiovascular mortality or hospitalisations. Results: Long term low dose allopurinol was associated with a significant worsening in mortality over those who never received allopurinol (relative risk 2.04, 95% confidence interval (CI) 1.48 to 2.81). This may be because low dose allopurinol is insufficient to negate the adverse effect of a high urate concentration. However, long term high dose (> 300 mg/day) allopurinol was associated with a significantly better mortality than longstanding low dose allopurinol (relative risk 0.59, 95% CI 0.37 to 0.95). This may mean that high dose allopurinol can fully negate the adverse effect of urate and return the mortality to normal. Conclusions: Long term high dose allopurinol may be associated with a better mortality than long term low dose allopurinol in patients with CHF because of a dose related beneficial effect of allopurinol against the well described adverse effect of urate. Further work is required to substantiate or refute this finding.

Xanthine oxidase inhibition for the treatment of cardiovascular disease: an updated systematic review and meta‐analysis

“…Several observational studies suggest that allopurinol use is associated with lower mortality but association does not prove causality 38, 39. Other treatments for gout have also been purported to have effects on cardiovascular outcome 40.…”

“…The production of UA by xanthine oxidase also generates free radicals that might adversely affect mitochondrial function and ATP production. XOIs might reduce free radical production, leading to improved left ventricular (LV) function and reverse LV remodeling and renal function 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. There is a substantial literature suggesting that serum UA concentrations are associated with worse cardiovascular outcomes 13, 14, 15.…”

Understanding Gout Beyond Doubt

“…Neutrophil phagocytosis leads to another burst of inflammatory mediator production. Subsidence of an acute gout attack is due to multiple mechanisms, including the clearance of damaged neutrophils, recoating of urate crystals, and the production of anti-inflammatory cytokines including, IL-1RA, IL-10, and transforming growth factor (TGF)-beta 17 . All this ultimately causes intense pain, redness and swelling around the joint area.…”

Canadian Cardiovascular Society Consensus Conference recommendations on heart failure update 2007: Prevention, management during intercurrent illness or acute decompensation, and use of biomarkers

“…Allopurinol may be started approximately two weeks after the acute episode is completed. Small studies have hypothesized that allopurinol may be beneficial in chronic heart failure, possibly due to its antioxidant properties, although this is has not been proven (84,(129)(130)(131)134).…”