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

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 3, May/June 2017 202 AFRICA
endothelial dysfunction in patients with diseases including
congestive heart failure, the metabolic syndrome, diabetes and
chronic kidney disease. In all cases, the improvement was
significant, between 25 and 100%.4 On the other hand, studies
on inflammation and lipid profile yielded controversial data. XO
inhibitors did not influence CRP levels in several studies, CRP
being decreased in only one.10 ICAM was also reduced in only
one of the studies.9 Fibrinogen, interleukin 6 (IL-6), vascular
endothelial growth factors (VEGF) and E-selectin levels were
not affected. 9 One study found an improved lipid profile, but two
further studies did not.8
Ziga et al. reported that in 40 hyperuricaemic patients, levels
of triglycerides, total cholesterol, low-density lipoprotein (LDL)
cholesterol and high-density lipoprotein (HDL) cholesterol were
slightly increased after three months of allopurinol treatment.11
The authors suggested that in patients with the metabolic
syndrome, lipid profile should be monitored after the initiation
of allopurinol treatment, as the atherogenic index is increased in
these patients. Renin and B-type natriuretic peptide (BNP) levels
were decreased by XO inhibitors, this finding being of special
relevance to ischaemic and heart failure patients.9,12
Angina pectoris
The use of allopurinol improves chronic stable angina. Angina
pectoris has a high prevalence of 5.7% inmen and 6.7% in women,
not all of them being referred for interventional cardiology. In
these patients, allopurinol could be useful to increase exercise
time, time to 1-mm ST depression, and time to angina.13 This
is the main reason why allopurinol is recommended when
classical anti-anginal drugs are contra-indicated or not efficient
in controlling angina. The previous assertion is in agreement
with the 2013 European Society of Cardiology guidelines on the
management of stable coronary heart disease, which recommend
600 mg/day allopurinol under the ‘other drugs’ heading.14
Allopurinol has been found to improve exercise capacity by
increasing ATP production for the same myocardial oxygen
supply. Therefore allopurinol increases not only exercise capacity,
but also the double product and peak effort.15 On the other hand,
classical anti-anginal drugs increase exercise capacity, but not the
double product or myocardial energy production.15
Other beneficial effects of allopurinol are related to
endothelial function and coronary vasoconstriction. Rajendra
et al. studied endothelial function assessed by forearm venous
occlusion plethysmography, flow-mediated dilation and pulse-
wave plethysmography in 80 patients with coronary heart
disease. Compared to the placebo group, allopurinol improved
endothelium-dependent vasodilation and completely eliminated
oxidative stress.16
In another study, Noman et al. investigated the effects of
high-dose allopurinol on exercise in patients with stable angina
pectoris.17 The study included 65 patients with positive stress
testing, in whom 600 mg/day allopurinol increased time to ST
depression from 232 to 298 seconds. The duration of exercise
was consequently increased from 301 to 393 seconds. The time
to chest pain was increased too, from 234 to 304 seconds, the
difference being highly significant. On the contrary, the effect
on the number of angina episodes/week or number of tablets of
glyceryl trinitrate/week was not significant in comparison with
placebo.
Unfortunately, there are further studies which do not
confirm the aforementioned results. They describe no significant
improvement of exercise capacity in patients with stable angina
treated with allopurinol.9,15
Rekraj et al. studied the effect of high-dose allopurinol on
left ventricular hypertrophy and endothelial function in patients
with chronic stable angina. Using 600 mg allopurinol daily, flow-
mediated vasodilation increased by 0.82 ± 1.8% at nine months,
from 4.1 ± 2.1% at baseline. On the other hand, in the placebo
group, the initial flow-mediated vasodilation of 5.68% decreased
by 0.69 ± 2.8% at nine months (p = 0.017).18 The data suggested
the need for long-term treatment with allopurinol in order to
obtain anti-atherosclerotic effects.
The same article showed a nine-month left ventricular mass
(LVM) and left ventricular mass index (LVMI) decrease of 5.2 g
and 2.2 g/m 2, respectively, in the allopurinol group, versus 1.3 g
and 0.53 g/m2 in the placebo group, the difference being highly
significant. They also determined the augmentation index (AIx),
which was lower in the allopurinol group, suggesting not only
improvement in endothelial function, but also less vascular
remodelling. The results suggest that allopurinol is useful in
hypertensive patients with ischaemic heart disease.
Agarwal et al. recently presented a meta-analysis of 10 studies
on the effects of allopurinol in 738 hypertensive patients. 19
Compared to the control group, allopurinol-treated patients
displayed a 3.3-mmHg systolic and a 1.3-mmHg diastolic blood
pressure decrease.
Other manifestations of ischaemic heart disease
There are many further studies on the effects of allopurinol in
ischaemic heart disease but data are insufficient to allow the
formulation of strong evidence-based guidelines.20 Beneficial
effects were reported mainly in patients with myocardial
revascularisation with coronary artery bypass surgery or
angioplasty post myocardial infarction.
Available data allow advocating a role for allopurinol in
decreasing the number of complications, including arrhythmias,
and improving myocardial function in revascularised patients,
sustained by experimental data on the effect of allopurinol on
cardiomyocyte apoptosis in rats after myocardial infarction. 20
Xiao et al. reported a decrease in apoptosis measured through
caspase activity in non-infarcted myocardial areas in rats with
infarction.21 The study suggests myocardial protection through
allopurinol, not only in chronic forms of ischaemic heart disease,
but also in acute coronary syndromes.
In 2010, Rentoukas et al . reported that acute myocardial
infarction patients submitted to primary percutaneous
angioplasty and treated with a loading dose of 400 mg
allopurinol followed by 100 mg daily for one month displayed
a more effective ST-elevation recovery and lower peak values
of troponin, CK-MB and creatine phosphokinase (CPK),
along with a 13% decrease in major adverse cardiac effects at
one-month follow up.22
In a recent review, Grimaldi-Bensouda et al. discussed the
impact of allopurinol on the risk of myocardial infarction and
compared the drug to colchicine. The myocardial infarction
OR in the allopurinol group was 0.80, compared to 1.17 in the
colchicine group.23
In a critical review, Robert et al. emphasised that the effects