What does the future hold for the patient with peripheral arterial disease?
Individuals with Peripheral arterial disease (PAD) have a significantly elevated risk of developing major cardiovascular complications, but, until recently, the atherosclerotic manifestation of PAD has largely been regarded as a local problem of limited blood supply in the lower limbs, and treatment has reflected this. The association between PAD and cardiovascular mortality suggests that treatment strategies should, however, take into account the systemic nature of atherosclerosis and focus on the management of recognized atherosclerotic risk factors.
This is reflected in national and international treatment guidelines, which recommend that patients with PAD should be targeted for aggressive atherosclerotic risk factor therapy. Although interventional and medical therapies are available, and are continuing to be developed, PAD patients are currently being undertreated, and there is, therefore, a need for unbiased and comprehensive reporting of treatment results and quality assurance, so that awareness is raised and the management of PAD is improved
Peripheral arterial disease (PAD), a disorder characterized by obstruction of arteries supplying the lower limbs, is an important manifestation of atherosclerosis, with a prevalence ranging from 3% for people under the age of 60, to 20% at age 75 and over. There is a higher incidence in men than in women up to the age of 70, after which the prevalence rates equalize. The most common symptom of PAD is intermittent claudication (IC), painful cramping in the leg or hip, particularly when walking, which eases when the muscles are rested.
Depending on the severity of symptoms (if any), mortality rates among patients with PAD have been shown to be 2–4 times greater than that of a sex- and age-matched control group without any atherosclerotic manifestations. This increased mortality may be attributed to the strong correlation between PAD and coronary heart disease (CHD), an association that is evident even in individuals without a history of CHD and without symptoms of claudication. Indeed, mortality rates among patients with PAD and patients with CHD are similar.
Until recently, atherosclerotic manifestations in the lower limbs have been regarded as a local problem of limited blood supply. Thus, treatment has been directed towards improving blood supply, or towards lifestyle changes, such as smoking cessation and initiation of exercise programmes. In a few patients, these measures are supplemented with medicines that are intended to relieve symptoms – some proving more effective than others. However, the association between PAD and cardiovascular mortality suggests that treatment strategies should take into account the systemic nature of atherosclerosis and focus on the management of recognized atherosclerotic risk factors.
This paper will focus on the treatment possibilities that are available today for the patient with PAD; whether the available treatment strategies are being adequately implemented and monitored; and how the quality of treatment for the patient with PAD can be improved in the future.
Treatment options for PAD
Interventional techniques
Improving blood supply to the lower limbs may involve vascular surgical treatment by endarterectomy and/or bypass surgery, or interventional treatment with percutaneous transluminal angioplasty (PTA), which today accounts for approximately 30% of re-vascularization procedures.
In contrast to coronary arteries, the vessels that are affected in PAD tend to be bent in some situations and straight in others. For example, the popliteal artery in the knee has to be able to bend more than 90°. Consequently, in order to treat a lesion that is located in such a vessel using endovascular techniques, one must use a stent that is also flexible. New, spiral-formed stents have the necessary ability to bend, and have the additional benefit of allowing side vessels to be kept open.
Other interventional techniques that have recently been developed include the abdominal aortic aneurysm (AAA) stent graft, which is introduced via the femoral artery and opened up inside the body, thereby excluding the aneurysm sac, reducing the pressure, and preventing rupture of the aneurysm. The main limitation of such a technique is the durability of the stent material, since a patient receiving an operation for an aneurysm may survive for 10 years or more.
The use of radiological techniques to visualize the vascular system, such as X-rays, ultrasound and magnetic resonance, has also greatly facilitated the practice of interventional therapies, and their use is likely to increase as methodologies become more refined.
The success of an interventional therapy is often expressed in terms of its patency, but this takes no account of the patient’s experience of the procedure and their pre- and post-operative quality of life. This was illustrated in a prospective, randomized trial in which PTA was compared with exercise training for the treatment of stable claudication. Fifty-six patients were randomized to one of the two treatments, and assessed for ankle/brachial pressure index (ABPI), treadmill claudication and maximum walking distance at 3-monthly intervals for 15 months, and at approximately 6 years follow-up (37 patients were available for long-term review). Although significant increases in ABPI were seen in the patients treated with PTA at all assessments up to 15 months, the most significant changes in claudication and maximum walking distance were seen in the exercise training group. At long-term follow-up, there was no significant difference between the groups.
New interventional techniques, mostly endovascular based, will continue to be developed and used in addition to adjunctive procedures and medications. However, the long-term effects of interventional treatment, such as balloon angioplasty and surgery, should be evaluated not only technically but also in terms of improvement in the patient’s symptoms (walking ability or quality of life). It is also important to remember that although interventional treatment may relieve the symptoms caused by atherosclerotic obstructive disease, it cannot cure the disease itself.
Drug therapies
Statins, angiotensin-converting enzyme (ACE) inhibitors and antiplatelet drugs have all been shown to reduce the risk of coronary events in patients with CHD. Due to the strong and independent association between PAD and cardiovascular mortality, guidelines of various national and international bodies recommend that patients with PAD should be targeted for aggressive atherosclerotic risk factor therapy.
Although data for the effects of lipid lowering in PAD patients are limited, what evidence there is from previous studies is encouraging. In the Cholesterol Lowering Atherosclerosis Study (CLAS), angiographic assessment demonstrated that patients treated with colestipol and niacin experienced more atherosclerotic regression and less atherosclerotic progression in the femoral arteries than those receiving placebo. Other studies have shown cholesterol lowering to be associated with a reduction in risk of IC. Retrospective analysis of data from the Scandinavian Simvastatin Survival Study (4S) supports these findings: in the subgroup of patients with PAD, over the median follow-up period of 5.4 years, the risk of new or worsening IC was reduced by 38% in the simvastatin group compared with the placebo group.
H. Sillesen
Department of Vascular Surgery, KAS Gentofte University of Copenhagen, N. Andersensuej, 2900 Hellerup, Denmark
Correspondence: Dr. H. Sillesen, Department of Vascular Surgery, KAS Gentofte University of Copenhagen, N. Andersensuej, 2900 Hellerup, Denmark. Tel. +45-39-77-3402; fax: +45-39-77-7614
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