New treatment options in intermittent claudication: the US experience.
Reference: Int J Clin Pract Suppl 2001;119:20-7
The goals of treatment in intermittent claudication are to modify cardiovascular
risk factors and to
reduce claudication pain, increase walking distance and improve quality
of life. Walking distance
in intermittent claudication can be improved both by exercise rehabilitation
and by
pharmacological treatments. At present, the only two drugs licensed in
the US for the treatment
of claudication symptoms are oxpentifylline and cilostazol. Although oxpentifylline
has been
shown to increase maximal and pain-free walking distance in a number of
trials, other studies call
its efficacy into question. Eight double-blind, placebo-controlled trials
have established that
cilostazol improves both maximal and pain-free walking distance in patients
with moderate to
severe intermittent claudication, with highly statistically significant
differences compared with
placebo. Cilostazol has also been shown to improve the physical dimensions
of quality of life.
Naftidrofuryl is licensed for the treatment of intermittent claudication
in Europe, but not in the US.
Some clinical trials have shown it to be effective in treating intermittent
claudication. Promising
new agents in the treatment of intermittent claudication include L-arginine,
propionyl-L-carnitine,
prostaglandins, and angiogenic growth factors such as vascular endothelial
growth factor and
basic fibroblast growth factor.
Cilostazol: a novel treatment option in intermittent claudication.
Reference: Int J Clin Pract Suppl 2001;119:11-8.
Cilostazol is a phosphodiesterase III inhibitor with antiplatelet, antithrombotic
and vasodilatory
effects. It raises plasma high-density lipoprotein cholesterol levels by
approximately 10% and
lowers plasma triglycerides by approximately 15%. Eight US/UK randomized,
multicentre,
double-blind, placebo-controlled trials lasting 12-24 weeks have been conducted
with cilostazol
50, 100 or 150 mg twice daily in more than 2,000 patients with moderate
to severe intermittent
claudication. In constant- or variable-load treadmill tests, cilostazol
increased maximal walking
distance by 28-100%, and pain-free walking distance by 45-96%. Comparable
changes for
patients on placebo were -10 to 30% for maximal walking distance and 9
to 50% for pain-free
walking distance. Responses were observed as early as the first observation
point of 2 or 4
weeks and increased with time. The response was greater for 100 mg twice
daily than for 50 mg
twice daily. For the 100 mg twice daily dose, there was no evidence of
a plateau in effect. In
both the US and the UK, cilostazol is indicated to increase walking distance
in patients with
intermittent claudication. Cilostazol is generally well tolerated. In clinical
trials, the most common
adverse effects were headache, palpitation, tachycardia, abnormal stools
and diarrhoea. Adverse
events were generally mild to moderate in intensity.
Intermittent Claudication.
Reference: Current treatment options in cardiovascular medicine.2001;3(3):167-180.
Intermittent claudication is the most common symptom in patients with peripheral
arterial disease
(PAD). As such, it is mandatory for clinicians to treat both the PAD-specific
symptoms (to
decrease functional impairment and thereby improve quality- of-life, as
well as to decrease rates
of amputation) and the underlying systemic atherosclerosis (and thereby
reduce cardiovascular
ischemic events, especially myocardial infarction and stroke). Most patients
with claudication can
successfully decrease their exertional limb symptoms via a combination
of exercise (preferably
supervised) and pharmacotherapeutic interventions (eg, cilostazol). Endovascular
revascularization currently serves as an effective therapy for patients
with high-grade stenoses of
the proximal limb arterial segments, (eg, the distal aorta, common iliac
artery, or external iliac
artery, and occasionally the proximal common femoral artery). Surgical
revascularization usually
is reserved for patients who present with severe aortoiliac disease in
whom long-term patency is
likely to be achieved (eg, aortobifemoral or femoral-femoral bypass) and
who have a low
cardiovascular perioperative ischemic risk. Patients who undergo successful
revascularization also
are likely to benefit from exercise rehabilitation programs. All patients
with PAD, of any severity,
must successfully normalize atherosclerosis risk factors and use antiplatelet
therapies. Such
interventions include complete smoking cessation, glycemic control, normalization
of blood
pressure (less than 130/90 mm Hg), and lowering of low-density lipoprotein
(LDL) cholesterol to
less than 100 mg/dL. Antiplatelet agents (eg, clopidogrel, aspirin) should
be prescribed to
decrease rates of cardiovascular ischemic events in all patients with PAD,
unless otherwise
contraindicated.
Assessment and management of intermittent claudication: importance of
secondary prevention.
Reference: Int J Pract Suppl 2001;119:2-9
Atherosclerotic peripheral arterial disease (PAD) is a common disorder
with a steep age-related
incidence that affects 5-10% of the over 55-year age group. Because of
the association with
atherosclerotic disease elsewhere, particularly coronary heart disease
(CHD), the ankle-brachial
pressure index (ABPI) correlates inversely with survival. Clinical management
centres around
detection, assessment, symptom relief and prevention of secondary cardiovascular
complications.
Non-invasive ultrasound and colour duplex techniques have revolutionised
the detection of PAD,
and the long-term surveillance of disease progression, while antiplatelet
therapy coupled with risk
factor modification (lipids, blood pressure and glycaemic control and smoking
cessation) are
aimed at reducing direct or indirect vascular complications, e.g. amputation
or CHD death. The
natural history of intermittent claudication, although troublesome and
disabling, often runs a stable,
fairly benign course, so the majority of patients (73%) are treated medically.
Selecting patients for
surgical revascularisation (angioplasty, bypass or endarterectomy) is guided
principally by the
severity of clinical symptoms, but discrete, proximal, short-segmental
lesions are the most
amenable to surgical intervention. In general, surgery is indicated to
relieve disabling symptoms
when medical therapy had failed; for treatment of symptoms of limb-threatening
ischaemia,
including rest pain, ischaemic ulceration and gangrene; and to remove or
bypass sources of
thrombo-embolism. Thus, medical therapies for symptom relief and secondary
prevention of
complications form the mainstay of treatment for three-quarters of patients
with uncomplicated
intermittent claudication.
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Volume
4, Number 6: June 2001
