Cardiovascular Journal of Africa: Vol 28 No 3 (May/June 2017)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 3, May/June 2017

AFRICA

203

of allopurinol on cardiovascular disease are mediated by XO

inhibitors via free radicals and inhibition of oxidative stress.

Gladden

et al.

studied the effect of allopurinol on systolic and

diastolic left ventricular function in rats with volume overload

from aorto-caval fistula.

Allopurinol increased left ventricular

(LV) contractility and ejection fraction, but did not alter LV

dilation and diastolic pressure/wall stress rate as a measure of

diastolic function, despite XO activity being increased in human

myocytes with volume overload.

The aforementioned data may

explain why, in the EXACT-HF study in hyperurcaemic heart

failure patients, allopurinol failed to improve LV ejection fraction,

symptoms, exercise capacity and time to hospitalisation.

Recently, Valbusa

et al

. reported an increase in incidence of

atrial fibrillation in type 2 diabetes patients with hyperuricaemia

(10.5% in 10 years) with an OR of 2.43, but there are insufficient

data to confirm that this increase could be prevented by using

XO inhibitors. To date, no trial has been conducted to examine

the effect of allopurinol on atrial fibrillation.

Beveridge

et al

. reported that allopurinol was associated

with significant functional improvement in older rehabilitation

patients, including those with cardiovascular disease.

The

improvement in functional status was demonstrated using the

Barthel score, which was higher in the allopurinol group (4.7 vs

3.6;

0.002). These findings could be attributed to the increase

in ATP production by allopurinol.

Sanchis-Gomar analysed post-exercise cardiovascular

markers of injury in 12 football players. They found that 300 mg

allopurinol before a football game had no significant effect on

these markers, except for promedulin levels, which were higher in

the placebo than in the allopurinol group.

Many controversial issues will be answered through the

CARES trial, which aims at studying the effects of allopurinol

and febuxostat in patients with gout and cardiovascular

co-morbidities.

This study includes 7 500 patients with

gout and cardiovascular disease, followed up for five years.

Cardiovascular end-points, composite cardiovascular death,

non-fatal myocardial infarction, non-fatal stroke, and unstable

angina requiring urgent coronary revascularisation will be taken

into consideration.

Conclusion

XO inhibitors have proven efficacy as second-line drugs in

patients with chronic stable ischaemic heart disease, and

are recommended in this setting by current evidence-based

guidelines. In other manifestations of ischaemic heart disease,

data are controversial and further investigation is warranted.

Dr M Zdrenghea was supported by a research grant from the Romanian

National Authority for Scientific Research CNCS – UEFISCDI, project

number PN-II-ID-PCE 2012-4-0417. Drs D Zdrenghea and D Pop contrib-

uted equally to this work.

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