The large body of
evidence
supporting the
cardiovascular
implications of
gout, clearly
suggests the
importance of
urate-lowering
treatment on the
progression and
clinical outcome
of cardiovascular
diseases
failure has been demonstrated in many different
studies either in terms of new onset of the disease
or more severe clinical outcome. 23,24
The results of the NHANES III survey have
reported a prevalence of congestive heart failure
ranging from 9.7% to 11% in patients with gout
compared with 1.8% (SE 0.16) of individuals
without gout. 9,25 Accordingly, the results from the
Framingham offspring study have reported a higher
incidence of clinical heart failure and a higher
mortality in patients with gout complicating heart
failure compared with heart failure without gout. 26
Thanassoulis et al 27 reported an increased risk of
death or re-hospitalisation for heart failure (adjusted
RR 1.63; 95% CI 1.48–1.80 and 2.06; 95% CI 1.39–3.06,
respectively) in a cohort of 25,090 subjects with
symptomatic heart failure and a remote history or
an acute episode of gout.
Gout medications and CVD outcomes
The large body of evidence supporting the
cardiovascular implications of gout, clearly suggest
the importance of urate-lowering treatment
(ULT) on the progression and clinical outcome of
cardiovascular diseases. According to the results
published by Krishnan et al, 28 the ULT can reduce
the rate of major CV events with outcome rates
comparable to non-gout individuals, whereas
patients not on treatment have significantly higher
rates of CVD. A significant cardioprotective effects
has been described for drugs as xanthine oxidase
inhibitors (for example, allopurinol) and colchicine
indirectly supporting the association between gout
and increased cardiovascular risk. 7 In particular, ULT
has been demonstrated to improve both the extent
of target organ damage and also the rate of major
CV complications even when most of the evidence
was collected in patients with hyperuricaemia,
with only a small number of studies addressing
the problem of gout. Farquharson and colleagues
investigated the effect of gout therapies in patients
with mild to moderate congestive heart failure
treated with increasing doses of allopurinol, (300,
600mg/day) 600mg, or placebo. 29 They demonstrated
that both doses of allopurinol dose-dependently
improved endothelial function significantly
better than placebo. Improvements in endothelial
function thus seemed to be a result of a reduction in
oxidative stress. 30 Interestingly, Chen et al 31 showed
that the use of ULT was associated with a reduction
in cardiovascular mortality in patients with gout
with a result that was comparable to that observed
in patients without gout.
The CARES study 32 has clearly demonstrated
the comparable safety profile of allopurinol and
febuxostat in high CV risk patients with gout
complicated by previous cardiovascular disease
(mainly CHD), even whether no conclusions can
be drawn about the effects of treatment on CV
prognosis according to study design (safety end-
points, no placebo control). However, an indirect
comparison with the results of other studies
involving the same population of patients (for
example, IMPROVE-IT), seem to suggest a lower rate
of major CV disease in treated patients with gout
and high cardiovascular risk profile.
More information on this issue is expected from
the conclusions of ongoing studies (FAST, ALL-
HEART, FORWARD; Table 1) as well as from results
of the clinical efficacy of newer compounds such as
lesinurad, the mechanism of action of which could
perfectly integrate with that of the available agents,
leading to significant protection against both the
articular and cardiac involvement in gout patients.
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