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Heart failure, allopurinol, and mortality

 

Clinical bottom line

High serum uric acid is probably an independent risk factor for cardiovascular disease. Patients with chronic heart failure and gout treated with long term low dose allopurinol had higher mortality than patients without gout, and with those on long term, high dose allopurinol.


Reference.


AD Struthers et al. Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study. Heart 2002 87: 229-234.


Method

Using the MEMO record linkage system with information on all drugs dispensed, hospitalisations, and deaths and their causes in Tayside, patients with defined congestive heart failure before 1993 were identified. Exclusion was renal failure. These patients were identified at July 1993 and followed to March 1999 for mortality.

Allopurinol was defined by dose (more or less than 300 mg a day) and duration (depending on whether allopurinol had been started before or since 1993). Various outcomes included all cause and cardiac mortality.

Results

There were 1,760 patients in all, most of whom (1,593) had never been prescribed allopurinol. Long term high dose allopurinol was taken by 47 patients, long term low dose by 48 and recent low dose by 72.

All cause mortality was similar in all groups, except in low dose long term allopurinol patients whose mortality was significantly higher. Cardiovascular mortality and hospital admissions were all significantly higher in the long term low dose group.

Comment

The point about this paper is that it examines an hypothesis (with independent evidence) that high serum urate is a cause of some cardiovascular mortality. In patients with chronic heart failure and gout, mortality should be higher in patients if untreated, but adequate treatment should reduce any excess mortality, thus bringing mortality of patients with chronic heart failure and gout back to that of chronic heart failure alone.

This is what happened. But long-term low dose allopurinol had higher all cause and cardiovascular mortality, probably because it did not sufficiently reduce serum urate levels.

This has nothing like the power of a randomised trial, but patients with both chronic heart failure and gout might be candidates for allopurinol doses of more than 300 mg daily.