Allopurinol as a Possible Oxygen Sparing Agent During Exercise in Peripheral Arterial Disease
Status:
Completed
Trial end date:
2012-07-01
Target enrollment:
Participant gender:
Summary
Peripheral arterial disease (PAD) is a common condition that arises due to the build up of
atheroma in the arteries supplying blood to the peripheral muscles and other tissues. This
imbalance between oxygen supply and demand becomes particularly apparent when patients with
the condition are walking. The pain and weakness they experience (mainly in the calf but less
commonly in the thigh) is known as intermittent claudication and resolves upon cessation of
exercise.
It is an important disease to study as it is (i) common (est. prevalence of symptomatic
intermittent claudication in Scotland of 4.5%) and (ii) those with it have a 1.6 times higher
relative risk of ischaemic heart disease. These patients also have a significantly higher
mortality than age-matched controls at around 12% per year.
There are two main aims of therapy - (i) to reduce the risk of cardiovascular events by way
of standard secondary prevention measures (smoking cessation, anti-platelet,
anti-hypertensive and cholesterol-lowering therapy, diabetic control) and (ii) to treat
symptoms.
Supervised exercise therapy has been shown to be beneficial in improving walking time and
distance in selected patients with leg pain from intermittent claudication with an overall
increase in walking distance of approximately 150 metres at three months.
There are numerous drug treatments available for consideration in PAD patients (mainly
cilostazol in the UK), but many of these have either undesirable side effects or no clear
evidence of benefit. The range of increase in walking distance on cilostazol was reported to
be a 50-76% increase over three months compared to 20% with placebo with some significant
improvements in Quality of Life (QOL) indicators, although with a significant number of
adverse effects (16% vs 8% on placebo) limiting therapy. The current cost (March 2010) is
£35.31/month.
Other options for therapy include angioplasty and bypass surgery. At present these are only
recommended for patients who fail to respond to medical therapy and have severely disabling
symptoms (in the absence of significant exercise-limiting comorbidities).