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


METHODS
Retrospective cohort study.


METHODS
Medicines Monitoring Unit, Ninewells Hospital, Dundee, UK.


METHODS
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.


METHODS
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 (> or = 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.
Struthers
A D
AD
Department of Clinical Pharmacology & Therapeutics, and the Medicines Monitoring Unit, Ninewells Hospital, Dundee DD1 9SY, UK. a.d.struthers@dundee.ac.uk
Donnan
P T
PT
Lindsay
P
P
McNaughton
D
D
Broomhall
J
J
MacDonald
T M
TM
D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage*; D002303:Cardiac Output, Low / Q000517:prevention & control*; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006074:Gout Suppressants / Q000008:administration & dosage*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D009026:Mortality; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D016166:Free Radical Scavengers; D006074:Gout Suppressants; D000493:Allopurinol