Peripheral Arterial Disease - Diagnosis and Treatment: A Systematic Review. 

Stockholm: Swedish Council on Health Technology Assessment (SBU); 2008 Nov. SBU Yellow Report No. 187.nSBU Systematic Review Summaries.



This report summarizes the results of SBU’s systematic review of the literature concerning methods of diagnosing and treating symptomatic peripheral arterial disease caused by atherosclerosis or arterial thrombosis in the lower extremities. The project did not include studies of methods to prevent or affect the development or progress of peripheral arterial disease. Many of those methods have been assessed by previous SBU reports: Smoking Cessation Methods (1998), Obesity – Problems and Interventions (2002), Moderately Elevated Blood Pressure (2004), Interventions to Prevent Obesity (2005) and Methods of Promoting Physical Activity (2007).


PERIPHERAL ARTERIAL DISEASE IS COMMON, PARTICULARLY IN THE ELDERLY, AND POSES A HIGH RISK OF LONG-TERM SUFFERING, AMPUTATION AND PREMATURE DEATH:Peripheral arterial disease is the result of ischaemia (insufficient blood flow) in the lower extremities. In the great majority of cases, the cause is atherosclerosis – which is among the most common diseases and one that rarely affects the blood vessels of the lower extremities alone, but rather the entire cardiovascular system. Thus, all patients who have symptoms of peripheral arterial disease should be assessed for risk of atherosclerosis. Peripheral arterial disease in its mild form may be limited to intermittent claudication, pain in the lower extremities that is triggered by exertion but that ceases during rest. When ischaemia is chronic, critical or acute – characterised by stenosed or occluded blood vessels – peripheral arterial disease increases the risk of tissue death (gangrene), amputation and premature death. Because atherosclerosis – the primary cause of peripheral arterial disease – can progress for a long time without producing any direct symptoms, the number of people who have the disease is unknown. The risk increases with age, and peripheral arterial disease occurs among an estimated 10% of people over 60 years. Half (more than 5,000) of the invasive procedures that are performed every year at Swedish hospitals for vascular diseases seek to restore blood flow in patients with various forms of peripheral arterial disease.


THE MOST URGENT PRIORITY FOR ALL VASCULAR DISEASES, INCLUDING THOSE IN THE LOWER EXTREMITIES, IS TO PERSUADE AND HELP PATIENTS TO STOP SMOKING:The correlation between smoking and peripheral arterial disease is very strong and has been documented by a large number of studies. The risk that a smoker will develop intermittent claudication is almost double that of developing angina pectoris. Smoking cessation reduces the risk of serious ongoing symptoms, amputation and death due to vascular complications. All treatment of peripheral arterial disease includes aggressively affecting the general risk factors for atherosclerosis, such as smoking, physical inactivity, overweight, hypertension, high lipids and high blood sugar. THE


SCIENTIFIC EVIDENCE FOR DIAGNOSIS AND TREATMENT OF PERIPHERAL ARTERIAL DISEASE IS LIMITED:Although a review of the literature identified several thousand articles, close examination revealed that only a small percentage of the studies met the criteria for quality and internal validity that have been established by health technology assessment and SBU in particular. As a result, the scientific evidence for the report’s conclusions is limited – or moderately strong at best. The benefits and risks of a number of the treatment methods reviewed by the project could not be assessed due to a lack of studies characterised by sufficient quality and internal validity. Such methods include anticoagulant therapy for intermittent claudication, oestrogen and testosterone therapy, hyperbaric oxygen therapy, spinal cord stimulation, electromagnetic therapy, ultraviolet light therapy and intermittent pneumatic compression. Scientific evidence is also lacking to assess the efficacy of vitamin E, vitamin B / folic acid, Omega-3, garlic and the Padma 28 herbal preparation.


WHILE THE PATIENT#ENTITYSTARTX02019;S EXPERIENCE OF SYMPTOMS SHOULD ALWAYS FORM THE BASIS OF DIAGNOSING AND TREATING PERIPHERAL ARTERIAL DISEASE, CLINICALLY RELEVANT STUDIES ARE GENERALLY LACKING THAT COMPARE HOW VARIOUS INTERVENTIONS IMPACT QUALITY OF LIFE:Peripheral arterial disease has a decisive – often disabling – impact on quality of life, the experience of which varies from person to person. Quality of life, which is among the key goals of all medical treatment, may be defined as an aggregate measure of physical and mental functioning, along with a sense of wellbeing and satisfaction. But clinical practice still takes only limited advantage of opportunities to assess quality of life, i.e., how the patient deals with daily activities and responds to treatment.


DIAGNOSTIC METHODS:The basic method for diagnosis and assessment of patients with symptomatic peripheral arterial disease includes assessing medical history with walking distance palpation, and a simple physical examination with a stethoscope, sphygmomanometer cuff and Doppler probe to compare blood pressure in the arms and legs. Such examinations, which may be performed at any health centre or hospital, can identify most patients with peripheral arterial disease. To more precisely locate stenoses and any thrombi requires additional assessment. While conventional angiography is still the most common approach, technical progress in recent years has generated a number of new methods for reliably diagnosing peripheral arterial disease. These methods are just as dependable as conventional angiography for designing a treatment strategy, but are gentler, easier, faster and less risky.Duplex ultrasonography has the same high reliability as conventional angiography when it comes to confirming or ruling out vascular disease in the lower abdominal aorta, as well as the arteries of the pelvis, thigh and knee. The scientific evidence is, however, weaker with respect to the certainty of the method for diagnosing changes in the lower leg and foot. Magnetic resonance angiography (MRA) using an injected contrast agent has the same high reliability as conventional angiography when it comes to confirming or ruling out vascular disease in the abdominal aorta below the kidneys, as well as the arteries of the pelvis and thigh. The scientific evidence is not as strong in terms of identifying stenosis in the arteries of the lower leg. MRA that does not use an injected contrast agent has the same high reliability as conventional angiography when it comes to confirming or ruling out vascular disease in the arteries of the thigh and lower leg. MRA is not as reliable for identifying changes in the abdominal aorta below the kidneys and in the pelvic arteries. Computed tomographic angiography (CTA) has the same high reliability as conventional angiography when it comes to confirming or ruling out vascular disease in all blood vessels, from the abdominal aorta to the arteries of the foot.


TREATING INTERMITTENT CLAUDICATION:No drug has been approved in Sweden for specifically treating peripheral arterial disease, and there is no therapy that can be said to cure the condition. Nevertheless, the following has been established:Physical training, walking or Nordic walking – particularly when organised or supervised – improves walking distance. Revascularisation, which is an intervention intended to restore or improve blood flow, should generally be avoided. But there is limited scientific evidence that open revascularisation in claudication patients with disabling symptoms may be somewhat more effective than walking training. Percutaneous transluminal angioplasty (PTA) with selective placement of a stent is cost-effective in comparison with other revascularisation methods that were reviewed. There is limited scientific evidence that Ginkgo biloba, a natural remedy, and levocarnitine can improve walking distance. There is limited scientific evidence that intravenous prostaglandin E1 increases walking distance.


TREATING CHRONIC CRITICAL LIMB ISCHAEMIA:Patients who have symptoms of critical limb ischaemia must receive prompt treatment to relieve the pain and minimise or eliminate the risk of deterioration leading to ulcers and tissue death (gangrene).Open or endovascular revascularisation using thrombolysis therapy or PTA should be offered when critical limb ischaemia may lead to amputation. Adjunctive therapy using a platelet inhibitor or vitamin K antagonist whose (warfarin) improves results after revascularisation therapy. Adjunctive therapy using a vitamin K antagonist causes more bleeding complications than platelet inhibitor. TREATING ACUTE LIMB ISCHAEMIA: Acute limb ischaemia is caused by abrupt occlusion of a major artery. The patient often experiences severe pain. Treatment must start immediately. The leg may have to be amputated.Immediate invasive treatment normally permits amputation-free survival for many years. There is no decisive difference between open surgical intervention and endovascular revascularisation through the blood vessels (thrombolysis therapy) in terms of amputation-free survival. Acute limb ischaemia often occurs at the end of life. In such cases, lower limb ischaemia results from a gradual slowdown in the functioning of the organs. Surgery is not indicated, and pain relief may be the proper treatment from a medical and compassionate point of view.


ETHICAL ASPECTS:Following are some of the ethical issues that must be taken into consideration when diagnosing and treating peripheral arterial disease: Reconstructive procedures for critical and acute limb ischaemia are often associated with the risk of serious complications, as well as death in some cases. Such risks must be weighed against the opportunity to improve health and quality of life. One problem in particular is that caregivers may have difficulty refraining from the use of new methods even when the documentation is substandard or incomplete. A patient’s lifestyle, such as continued smoking, must not lead to discriminatory treatment. While attempts to avoid amputation are a worthy goal, they must be weighed against risks and suffering in patients for whom it may turn out to be necessary after all. Resource utilization is also an ethical issue in such cases. SURVEY OF CLINICAL PRACTICE: Diagnosis, medical treatment and referral procedures for peripheral arterial disease patients in primary care can be improved. The disease is an uncommon diagnosis in Swedish primary care. Many patients are referred for diagnosis and assessment prior to possible intervention, but only a few undergo invasive treatment. SBU’s survey of clinical practice also reveals major regional differences in the number of patients who are referred for such diagnosis and assessment. Educational efforts, as well as guidelines for diagnosis and treatment of peripheral arterial disease in primary care, would raise awareness about patients with vascular disease who are at high risk of cardiovascular disease and death. ASSESSMENT AND


REPORTING:Major inadequacies remain when it comes to assessing new technologies. Systematic efforts in that area should be given high priority. The results of treatment should be reported to, and compiled in, a central registry. For the past 20 years, most vascular surgery – including radiological interventions such as throm- bolysis therapy and PTA – has been reported to the Swedish Vascular Registry (Swedvasc). Amputation due to peripheral arterial disease is however not systematically reported to the registry.


RESEARCH NEEDS:Multicentre randomised trials could be arranged in Sweden to address two key questions:Which therapy is better for intermittent claudication – intervention or walking training and best medical treatment? Which therapy is better for critical limb ischaemia – surgical/endovascular intervention or best medical treatment?