Arterial occlusive disease peripheral I73.9

Peripheral arterial occlusive disease (PAD) is a condition that limits blood flow to the arteries that supply the extremities, or more rarely to the aorta. This can be gradual (due to a stenosis) or complete (occlusion).

In about 95% of cases, chronic PAD is caused by arteriosclerosis or its symptomatic form atherothrombosis, one of the most common diseases with a complex, constantly progressive course. All regions of the body can be affected. Myocardial infarction, stroke and PAVK are merely different manifestations of one and the same disease.

Peripheral arterial occlusive diseases (pAVK) can be classified as follows:

• acute peripheral arterial occlusive diseases (apVK)
• chronic peripheral arterial occlusive diseases (cpVK)
• chronic peripheral arterial occlusive disease of the extremity arteries
• Special case: Diabetic foot syndrome

In Germany, the clinical classification of PAVK according to symptoms is usually based on the stage classification of Fontaine. In the Anglo-Saxon world and internationally, the Rutherford classification is in scientific use.

The prevalence (measured with the ABI) is 3-10%. From the age of 70 it rises to 15-20%. The global prevalence is estimated at about 202 million people. The incidence is tending to rise, especially in low and middle income countries (about 30% increase in 2000-2010).

The ratio of asymptomatic ABI patients to symptomatic claudication patients (who predominantly, but not always, have lowered ABI values) is about 4:1 regardless of age, and the prevalence of intermittent claudication increases from 3% in 40-year-old patients to 6% in 60-year-old patients.

In younger age groups the claudication is more frequent in men, in the higher age groups there are hardly any gender-specific differences. When PAVK is diagnosed, women are usually older, more often overweight and more often have CLI and vascular occlusion, men are more often smokers.

Mostly genetic and age-related components as well as diabetes mellitus, inflammatory vascular diseases. Risk factors are: advanced age, genetic family predisposition, male sex, hypertension, smoking, diabetes mellitus, hypercholesteinaemia and hypertriglyceridaemia, hyperfibrinogenaemia.

Inflammatory, genetic and traumatic causes (altogether 5% of all PAVK cases) become rarer with increasing age, but embolic events (cardiac or arterial) occur more frequently.

In the presence of a manifestation of atherothrombosis (e.g. PAVK), these are (high-) risk patients with a high risk of morbidity and mortality, also with regard to events in another vascular system. Vascular patients with previous ischemic events have a significantly increased risk of further cardiovascular events such as heart attack or ischemic stroke.

In addition to the classifications according to Fontaine and Rutherford, PAVK can be divided into the stage of intermittent claudication (CI) with stress-related pain and the stage of critical limb ischemia (CLI) with resting pain and ulcers.

The most severe form of PAVK is tissue loss (leg infarction) with the threat of amputation of the affected extremity. In the stage of CLI there is a significantly increased 1-year risk of a major amputation in the absence of revascularisation.

• Anamnesis (in particular stress pain, if necessary when climbing/ climbing stairs, resting pain if necessary when elevated)
• Inspection (injuries, mycosis, dystrophic/ atrophic skin growths)
• Pulse palpation of the entire extremity, auscultation (stenosis sounds distal to the stenosis), positioning sample.
• Ankle-Arm-Index (ABI): Measurement of the perfusion pressure of the aa. dorsalis pedis and tibialis anterior. Determination of the perfusion index from osseous artery pressure divided by arm artery pressure (normal > 0.9). Systolic pressures lower at the feet than at the arms are suspicious of an arterial obstruction. The exception is mediasclerosis in diabetics, which reduces compressibility and can lead to falsely increased perfusion pressures.
• If necessary, toe artery pressure measurement in case of ABI > 1.3 and/or known mediasclerosis
• Among the diagnostic imaging procedures, color-coded duplex sonography (FKDS) is the first-choice diagnostic method for clarifying the aorta and the pelvic and leg arteries.
• Further imaging diagnostics such as contrast-enhanced MR angiography, CT angiography, arterial digital subtraction angiography (DSA) are only indicated if there is a therapeutic consequence.
• Other angiological examination methods: treadmill ergometry (diagnosis: city II; 3.6 km/h speed, 10% incline), venous occlusion plethysmography, acral oscillography, thermography.

Causes of stenosing and/or occlusive arterial lesions in the lower extremities that can trigger a claudication (according to Lawall et al. 2015):

• Arteriosclerosis
• Vasculitis
• Congenital or acquired vascular malformations
• Fibromuscular dysplasia
• Peripheral Embolism
• Cystic adventia degeneration
• Compression Syndromes
• Vascular tumor
• pseudoxanthoma elastica
• Trauma or radiation damage
• spinal claudication
• venous claudication

In principle, there is the invasive lumen-opening and the conservative therapy direction. Thrombarteriectomy or bypass surgery as well as methods of interventional radiology (percutaneous transluminal angioplasty, balloon dilatation, laser recanalization, recanalization by means of milling) can be considered in about 35% of patients. Conservative methods depend on the general condition of the patient and the stage of AVK:

• Physical measures such as walking training in Stad. II (formation of collaterals, especially effective in femoral superficial artery occlusion) and deep storage in stadium II. III and IV.
• Iso- and hypervolaemic haemodilution (after or without bloodletting administration of hydroxyethyl starch to thin the blood).
• Therapy with vasoactive substances (parenteral administration of prostaglandin derivative E1 and prostacyclin iloprost for 4 weeks). An effective increase in walking distance was demonstrated in RCT only for cilostazol and naftidrofuryl. Substances such as pentoxifylline, L-arginine, buflomedine or ginkgo biloba have not provided sufficient evidence for a clinical benefit in claudication.
• Suitable local treatment, mainly in Stad. IV after Fontaine.

Dermatologically relevant therapy see below chronic arterial occlusive disease of the extremity arteries.

Recommendations for conservative therapy, revascularization and aftercare in PAVK (Lawall H et al. 2016)

• Smokers should be offered a programme of medical care, group therapy and nicotine stop and nicotine replacement.
• For secondary prevention of cardiovascular events, therapy with CSE inhibitors (statins) for PAVK and an antiplatelet inhibitor (ASS, clopedigrel) for symptomatic PAVK is indicated.
• Structured gait training under supervision and under regular guidance should be offered to all PAVK patients with intermittent claudication as part of the basic therapy.
• Cilostazol or Naftidrofuryl should only be used in the stage of claudication if the quality of life of the patients is considerably reduced, the walking distance is less than 200m and walking training is not possible or only possible to a limited extent.
• Patients with critical ischemia and infection should receive systemic antibiotic therapy.
• Endovascular procedures should be offered to patients with intermittent claudication if the patient has been informed in detail about the advantages of modifying his risk factors and about structured walking training, and if the occlusion processes appear suitable for endovascular treatment.
• Closure processes of the aorto-iliac arteries should first be treated endovascularly, regardless of the TASC stage. The patient's concomitant diseases and preferences as well as the quality of vascular surgical and endovascular care should be considered.
• In patients with critical limb ischemia (CLI), endovascular treatment of inflow and subsequent outflow lesions should be preferred if the same symptomatic improvement can be achieved in the short or long term as with vascular surgery.
• Closure processes of femoro-popliteal arteries should be treated endovascularly at first, independent of the TASC classification. If the criteria "long closure length", = TASC D, no increased surgical risk, not significantly limited life expectancy (>2 years) and availability of a donor vein are met, bypass surgery should be preferred.
• Vascular surgery options should be used in more complex, long-distance occlusion of the infrapopliteal arteries, in case of failure of endovascular treatment, or if clinical symptoms persist, or if a suitable bypass vein is available.
• All patients should receive pre-peri- and post-operative/interventional ASA (100mg), or clopedigrel. Treatment should be long-term.
• After infrainguinal endovascular therapy with stent implantation, the temporary combination of ASA and clopedigrel may be recommended to improve the "openness rate".
• Oral anticoagulants (OAZ) should not be routinely used in patients with infrainguinal, femoropopliteal or distal venous bypass.
• With regard to their symptoms (walking performance, pain at rest, trophic disorders), patients with PAVK should be routinely followed up.

• asymptomatic PAVK: A pathological ABI finding (both decreased and increased) is an independent indicator of cardiovascular morbidity and mortality. There is a direct correlation between pathologically decreased ABI and increased ABI: the lower the ABI, the higher the cardiovascular morbidity and mortality. 5-year mortality on average 19%.
• symptomatic PAVK: in approx. 25% spontaneous improvement of symptoms, in approx. 30-50% stable findings, in approx. 30% progress of symptoms. The fate of patients with claudication is determined by cardiac and cerebral events. The risk of a myocardial infarction is three times higher, the risk of a stroke four times higher. The risk of critical limb ischemia is low (2% amputation within the next 10 years). 5-year mortality on average 24%.

Ozone therapy, low-dose mixture of medical oxygen and ozone (0.05 to max. 5 % ozone content) in combination with phytotherapeutic measures, especially gingko preparations. The low-dosed ozone therapy can be applied systemically as ozone-oxygen-own-blood therapy or transcutaneously, e.g. ozone negative pressure fumigation, ozonated water or ozone cream. If necessary, combination with phlebotomy therapy.

Physicaltherapy: avoidance of vasoconstrictor noxious substances such as nicotine, exercise therapy, especially in the early to middle stages of the disease (Fontaine I-IIb), walking training, toe standing exercise, Nordic walking. Nutritional therapy: weight reduction, avoidance of carbohydrate-rich foods, saturated fats, excessive calorie intake.

Staging according to Fontaine and pathogenetic findings

Phytotherapeutics are primarily used in stage IIa. Partial successes could also be observed with them in stage IIb (Schilcher). Preference should be given to ready-to-use drugs which are standardized to certain minimum contents of efficacy-determining ingredients such as rutin or ginkgolides.

Gingko leaf special extracts(Gingko biloba folium) are the drug of first choice. Clinical studies according to GCP guidelines are only available with standardised gingko leaf extracts (primarily with Tebonin® preparations), which showed positive results in terms of increased walking distance in patients with peripheral arterial occlusive disease (Schilcher 2015).

Furthermore, buckwheat extracts (buckwheat herb-Fygopyri herba) with a high rutin content are also used adjuvantly.

Gingkgo therapy is successfully reinforced by drinking an additional 2-3 cups of buckwheat herb tea as a substitute for black coffee or black tea (Schilcher H 2015) .

In Switzerland, a mixture of 19 herbs, 1 resin and 1 mineral, the preparation Padma 28 from the manufacturing company Padma AG, has been approved since 1977. Due to the highly toxic aconite tuber contained in the original, this preparation is not approved in Europe. Padma Circosan, on the other hand, is available in Europe without the aconite tuber. Recent studies have shown a significant increase in walking distance of more than 100 m in 20% of patients with intermittent claudication.

The evidence-based data situation on PAVK is only moderately good. There is a lack of larger randomized controlled trials (RCT) on important topics of endovascular and surgical therapy, drug follow-up and aftercare.

The importance of PAVK is underestimated by doctors and patients.
Patients with PAVK are undertreated with regard to their risk factors and concomitant diseases.

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2. Lawall H et al. (2015) AWMF guideline PAVK
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4. Schilcher H (2015) Phytopharmaceuticals in cardiovascular diseases. In: Guide to phytotherapy. Urban and Fischer Publishers Munich, pp. 414-415.

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