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Patients with peripheral artery disease and diabetes mellitus are vulnerable with an increased risk for morbidity, amputation and mortality compared to non-diabetic patients with peripheral artery disease. Despite huge efforts of the health care system diabetes mellitus still represents an important risk factor, also in people with peripheral artery disease. Regardless of the presence of diabetes mellitus people are often not aware of peripheral artery disease or do not achieve optimal therapy. Further, only few people with peripheral artery disease consult an angiologist or vascular surgeon. Aiming to reduce morbidity and mortality prevention, early detection and optimal therapy of peripheral artery disease and diabetes mellitus are crucial factors in adequate health-care management.MORBIDITäT UND MORTALITäT.: Patienten mit peripherer arterieller Verschlusskrankheit (pAVK) und Diabetes mellitus stellen eine vulnerable Patientengruppe dar. Sie weisen im Vergleich zu pAVK-Patienten ohne Diabetes eine erhöhte Morbidität und eine gesteigerte Mortalität auf. DIABETES MELLITUS – EIN RELEVANTER RISIKOFAKTOR FüR AMPUTATIONEN.: Das Vorliegen eines Diabetes mellitus stellt bei Menschen mit einer pAVK ein erhebliches Risiko für eine Amputation dar. Die Inzidenz von Major-Amputationen bei Diabetikern ist nach einer aktuellen Studie 10-mal und von Minor-Amputationen 15-mal höher als bei Nichtdiabetikern. Eine Amputation bei Menschen mit Diabetes mellitus hat zudem einen erheblichen Einfluss auf die Morbidität und Mortalität. OPTIMIERUNG DER PATIENTENVERSORGUNG NOTWENDIG.: Trotz großer Anstrengungen im Gesundheitssystem repräsentiert der Diabetes mellitus weiterhin einen bedeutenden Risikofaktor, auch bei Menschen mit pAVK. Unabhängig vom Vorliegen eines Diabetes mellitus wird eine pAVK wiederum bei betroffenen Menschen oftmals nicht erkannt oder nicht adäquat therapiert. Nur wenige Menschen mit pAVK werden gefäßmedizinisch betreut. Zur Reduktion von Morbidität und Mortalität sind Prävention, frühzeitige Detektion sowie eine optimale Therapie von pAVK und Diabetes mellitus allerdings essenziell.

Patients with peripheral arterial disease (PAD) often have polyvascular atherosclerosis and are at increased risk of major adverse cardiovascular events (MACE), such as cardiovascular death, myocardial infarction or stroke, and major adverse limb events (MALE), such as amputation and acute limb ischemia. Therefore, the aim of conservative treatment is the reduction of MACE and MALE. In patients with intermittent claudication, the aim is also to extend walking distance. Management of risk factors includes smoking cessation, statin therapy, reduction of low-density lipoprotein cholesterol (target 55 mg/dL and reduction to at least 50% of baseline value), normalization of blood glucose and treatment of arterial hypertension (target 140/90 mm Hg). Moreover, antithrombotic treatment should include antiplatelet therapy (acety salicylic acid 100 mg or clopidogrel 75 mg). In patients at high thrombotic risk and low bleeding risk combination of acetlylic acid 100 mg and rivaroxaban 2 × 2.5 mg is indicated. In patients with intermittent claudication exercise therapy is highly recommended. Despite the high risk, in particular patients with PAD are often undertreated in clinical practice.Patienten mit einer peripheren arteriellen Verschlusskrankheit (PAVK) haben häufig eine polyvaskuläre Atherosklerose und ein hohes Risiko für „major adverse cardiovascular events“ (MACE) wie kardiovaskulären Tod, Myokardinfarkt und Schlaganfall sowie für „major adverse limb events“ (MALE) wie Amputation und akute Extremitätenischämie. Die konservative Therapie hat zum Ziel, MACE und MALE zu reduzieren und bei Patienten mit Claudicatio intermittens die Gehstrecke zu verlängern. Bei der Modifikation der kardiovaskulären Risikofaktoren werden das Einstellen des Rauchens, eine Statintherapie, die Reduktion des Low-density-lipoprotein-Cholesterins (Zielwert 55 mg/l und Senkung um mehr als 50 % im Vergleich zum Ausgangswert), eine normoglykämische Blutzuckereinstellung und die Behandlung eines Bluthochdrucks (Zielblutdruck ≤ 140/90 mm Hg) empfohlen. Außerdem sollte ein Thrombozytenaggregationshemmer (Acetlysalicylsäure 100 mg oder Clopidogrel 75 mg) gegeben werden. Bei hohem thrombotischem Risiko und niedrigem Blutungsrisiko wird Acetylsalicylsäure 100 mg in Kombination mit Rivaroxaban 2‑mal 2,5 mg empfohlen. Bei Vorliegen einer Claudicatio intermittens ist Gehtraining zur Verbesserung der Gehstrecke indiziert. Trotz des hohen Risikos werden im klinischen Alltag gerade Patienten mit einer PAVK nicht konsequent genug behandelt.

Patients with lower extremity arterial disease are at increased risk for cardiovascular events. Antithrombotic therapy improves prognosis in these patients especially after peripheral revascularization. After endovascular revascularization duale anti-platelet therapy with Aspirin and Clopidogrel is used for up to 3 months in most cases, although there is only little evidence for this practice. Following peripheral bypass grafting most guidelines recommend single anti-platelet therapy. In some patients, anticoagulation with Vitamin K antagonists or dual anti-platelet therapy is indicated. But this practice is also based on small studies. The Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease (VOYAGER PAD) study is the largest randomized trial concerning antithrombotic therapy after peripheral revascularization. In total 6564 patients were included after successful surgical or endovascular lower-extremity revascularization. Rivaroxaban 2.5 mg twice daily plus Aspirin 100 mg reduced cardiac and peripheral events compared with Aspirin 100 mg alone with increased risk for relevant but not for critical bleeding complications. In addition to antithrombotic medication risk factor management and regular follow-up examinations are important improve long-term prognosis after peripheral revascularization.In Analogie zur Koronarintervention wird nach Katheterinterventionen peripherer Gefäße meist passager eine duale Thrombozytenaggregationshemmung (TZAH) mit ASS 100 mg und Clopidogrel 75 mg durchgeführt. Größere Studien zu diesem Vorgehen fehlten bisher und die Empfehlungen der aktuellen Leitlinien haben den Charakter eines Expertenkonsens.Nach peripherer Bypassanlage empfehlen die aktuellen Leitlinien in der Regel die Monotherapie mit einem TZAH (ASS 100 mg oder Clopidogrel 75 mg). In Einzelfällen wird bei venösen Bypässen eine orale Antikoagulation oder bei Kunststoffbypässen eine duale TZAH eingesetzt. Diese Empfehlungen beruhen jedoch auf wenigen, teils kleinen Studien. DUALE GERINNUNGSHEMMENDE THERAPIE MIT NIEDRIGDOSIERTEM RIVAROXABAN UND ASS: Die VOYAGER-PAD-Studie ist mit 6564 Patienten die größte randomisierte Studie zur gerinnungshemmenden Therapie nach Revaskularisation. Es wurde das Konzept einer niedrigdosierten Rivaroxaban-Gabe (2-mal 2,5 mg) plus ASS 100 mg nach erfolgreicher peripherer Revaskularisation untersucht. Die Studie zeigte unter der Kombinationstherapie im Vergleich zur Therapie mit ASS 100 mg allein eine signifikant niedrigere Inzidenz des kombinierten Endpunkts aus akuter Extremitätenischämie, Amputation, Myokardinfarkt, ischämischem Schlaganfall oder Tod aus kardiovaskulärer Ursache. Getriggert wurde dieses Ergebnis primär durch die Reduktion von akuten Gefäßverschlüssen. Es kam zwar insgesamt zu mehr klinisch relevanten Blutungen unter der Kombinationstherapie, eine Erhöhung von intrazerebralen oder vital bedrohlichen Blutungen zeigte sich jedoch nicht. Wenn man Risiko und Nutzen in Bezug setzt, dann verhindert in einer Population von 10 000 Patienten die zusätzliche Gabe von Rivaroxaban 2-mal 2,5 mg pro Jahr 181 primäre Endpunkte auf Kosten von 29 relevante Blutungen.

Lower extremity arterial disease (LEAD) is a frequent manifestation of atherosclerosis with a high risk for cardiovascular events. The measurement of the ankle-brachial index (ABI) should be used as a screening method for LEAD. A differentiation is made between a stable stage of intermittent claudication and the stage of critical limb ischemia. The control of cardiovascular risk factors is crucial. Particular emphasis should be placed on smoking cessation and lipid-lowering treatment with statins and a target low-density lipoprotein (LDL)-cholesterol level of55 mg/dl as a core element. In patients with symptomatic LEAD an inhibition of platelet aggregation is indicated. In addition to treatment with clopidogrel 75 mg or with acetylsalicylic acid (ASS) 100 mg in high risk patients the combination of ASS 100 mg and rivaroxaban 2 × 2.5 mg can be indicated. In critical limb ischemia revascularization (percutaneous intervention, operation) is always indicated to prevent amputation. First-line treatment in patients with intermittent claudication is exercise training. Revascularization can be indicated in patients with a severe limitation of walking distance.

Peripheral arterial occlusive disease is a frequent and chronic vascular disorder mostly affecting the lower limbs and caused by fibrous plaques in arteries that can result in stenoses and thrombi. Patients suffering from this condition show a high risk for cardiovascular complications of the complete arterial vascular system, especially post-procedural. Thus, there is a need to optimize anti-thrombotic therapy. Data on multiple antiplatelet aggregation therapy including new drug classes are expected in the coming years. In addition, recent studies showed that direct oral anticoagulation provided clinical advantages combined with a reasonable safety profile. Management of risk factors such as overweight and nicotine and correction of metabolic disorders are not to be ignored and the background to further therapy. All treating physicians should be aware of these aspects to guarantee an optimal care and motivation of their patients.Die periphere arterielle Verschlusskrankheit ist eine häufige, chronische Störung der arteriellen Durchblutung v. a. der unteren Extremitäten, wobei fibröse Plaques der Gefäßwand zu Stenosen und Thrombenbildung führen. Bei betroffenen Patienten besteht ein hohes Risiko für kardiovaskuläre Komplikationen im gesamten arteriellen Gefäßsystem, auch nach dortigen Eingriffen. Daher besteht Optimierungsbedarf bei der antithrombotischen Therapie. Zur Mehrfach-Thrombozytenaggregationshemmung durch neue Arzneimittelklassen werden in den nächsten Jahren Studiendaten erwartet. Aktuelle Studien zeigten bei Hemmung der Gerinnungskaskade durch direkte orale Antikoagulanzien klinische Vorteile bei vertretbarem Sicherheitsprofil. Grundlage medikamentöser Therapie bleibt das Management von Risikofaktoren wie Übergewicht und Nikotin sowie die Korrektur metabolischer Störungen. Diese Aspekte sollten den behandelnden Ärzten bekannt sein, um eine optimale Versorgung und Motivation der Patienten zu erreichen.

Patients with peripheral artery disease are at high-risk for cardiovascular events. Anti-thrombotic treatment is very important for secondary prevention. In symptomatic patients single antiplatelet therapy with clopidogrel or Aspirin is recommended. After peripheral revascularisation transient dual antiplatelet therapy is widely used although there is only little evidence. Following peripheral bypass surgery most patients are treated with single antiplatelet therapy, in some cases (prostetic bypass grafts) dual antiplated therapy can be useful and selected patients with complex venous grafts might profit from anticoagulation with vitamin K antagonists.The recent publication of the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) study showed relevant reduction of MACE (Major Adverse Cariac Events) and MALE (Major Adverse Limb Events) for the combined therapy of rivaroxaban 2 × 2,5 mg compared to Aspirin 100 mg with increased risk for gastrointestinal bleeding. In the current VOYAGER PAD (Vascular Outcomes Study of Aspirin along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) study this concept is tested after peripheral revascularisation.Die aktuellen deutschen und europäischen Leitlinien empfehlen bei Patienten mit einer peripheren arteriellen Verschlusskrankheit (PAVK) die Monotherapie mit einem Thrombozytenaggregationshemmer (ASS 100 mg oder Clopidogrel 75 mg).In der COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) -Studie wurde Patienten mit PAVK 2 × 2,5 mg Rivaroxaban zusätzlich zu ASS 100 mg gegeben. Dies führte zur signifikanten Reduktion kardiovaskulärer Ereignisse (MACE = Major Adverse Cardiovascular Events) wie kardiovaskulärer Tod, Myokardinfarkt und Schlaganfall. Ebenfalls signifikant reduziert wurden periphere Ereignisse (MALE = Major Adverse Limb Events) wie ischämiebedingte Major-Amputation und eine akute schwere Ischämie.Liegt bei Patienten mit einer PAVK die Indikation zur oralen Antikoagulation vor (z. B. bei Vorhofflimmern), empfehlen die aktuellen deutschen und europäischen Leitlinien die Monotherapie mit oralen Antikoagulantien ohne zusätzliche Thrombozytenaggregationshemmung.Nach peripherer Intervention wird in Analogie zur Koronarintervention meist passager eine duale Plättchenhemmung durchgeführt. Nach peripherer Bypass-Anlage wird in der Regel die Monotherapie mit einem Thrombozytenaggregationshemmer empfohlen. In Einzelfällen kann bei komplexem Venenbypass eine orale Antikoagulation und bei Kunststoffbypass eine duale Plättchenhemmung eingesetzt werden.

The guideline of the European Society of Cardiology recommends an LDL-C target 70 mg/dL or a 50 % reduction in patients with manifest peripheral arterial disease (PAD) as well as in CHD or cerebrovascular disease when the baseline LDL-C is between 70 and 135 mg/dL. Application of a PCSK9 inhibitor allows target attainment for those patients who do not achieve this under maximal conventional therapy with a statin in combination with ezetemib. In the Fourier study, patients with PAOD who had neither a myocardial infarction nor a stroke at admission of the study had a significant risk reduction (RR) of both cardiovascular (RR = 0.67, 0.47 - 0.96, p = 0.0283) as well as extremity endpoints (RR = 0.43 (0.19 - 0.99; p = 0.042). In Germany these patients are primarily seen by angiologists. This group of vascular specialists is specifically mentioned in the decision of the Federal Joint Committee as one of those who may indicate treatment with PCSK9 inhibitors.Die Leitlinie der Europäischen Gesellschaft für Kardiologie empfiehlt bei Patienten mit manifester peripherer arterieller Verschlusskrankheit (PAVK) ebenso wie bei KHK oder zerebrovaskulärer Erkrankung einen LDL-C-Zielwert 70 mg/dL oder eine Reduktion um 50 %, wenn der Ausgangswert zwischen 70 und 135 mg/dL liegt. Die Applikation eines PCSK9-Inhibitors ermöglicht die Zielwerterreichung für viele Patienten, die dies unter einer maximalen Statintherapie in Kombination mit Ezetemib nicht erreichen. In der Fourier-Studie konnte für Patienten mit PAVK, die bei Studieneinschluss weder einen Myokardinfarkt noch einen Apoplex erlitten hatten, eine deutliche Risikoreduktion (RR) sowohl der kardiovaskulären (RR = 0,67; 0,47 – 0,96; p = 0,0283) als auch der die Extremität betreffenden Endpunkte (RR = 0,43; 0,19 – 0,99; p = 0,042) erreicht werden. Diese Patienten werden insbesondere bei Fachärzten für Angiologie erkannt und diese Facharztgruppe ist im GBA-Beschluss als Verordner speziell genannt.

Basic diagnostics includes inspection of the skin, palpation of leg and foot pulses and determination of the ankle-brachial-index. The hemodynamic relevance of the circulation problem is important for the therapeutic decision. For its determination several noninvasive procedures are available. Treadmill test can help to differentiate between vascular and other causes of walking limitation.

Peripheral artery disease is characterized by a limited blood circulation caused by stenosis or occlusion of peripheral arteries of the extremities. It is considered as a marker-disease of an advance atherosclerosis. Comorbidity with other manifestations of atherosclerosis like myocardial infarction or stroke is high.

Therapeutic goals are reducing cardiovascular risk and and improving the circulation in the leg. Therapeutic options are surgical and endovascular procedures as well as conservative treatment. The main focus for patients with intermittent claudication is to enhance quality of life. Patients with critical ischemia however are threatened by the loss of an extremity. In these cases, a conservative treatment is usually not sufficient and circulation must be quickly ameliorated by an endovascular or surgical procedure.

A 56 year old person presents with pain when walking. A peripheral artery disease in the iliacic vessels is diagnosed. Endovascular therapy results in a significant improvement. The following conservative treatment aims at reducing the cardiovascular risk. Especially stopping smoking turns out to be hard to achieve.

World wide increase of diabetes compound with diabetic foot syndrome becomes a challenge in vascular surgery to avoid limb loss. In diabetics a special pattern of atherosclerosis is prevalent with disease limited to the infrageniculate arteries but sparing inflow vessels and distal tibial and pedal arteries. This provides short bypass grafting from popliteal to tibial and pedal arteries, a concept first described by F. Veith in 1981.Diabetics with severe atherosclerotic disease and limb-threatening ischemia got general evaluation and vascular imaging. Falling in this special category the patients underwent short vein bypass grafting originating at the first or third popliteal segment extending to the tibial or pedal arteries. Follow up of patency and limb salvage was nearly complete.From 1988 to 2001 124 diabetics received 140 vein bypass grafts for limb salvage, 95.7% already preoperatively with foot necrosis. Operative mortality rate was 1.4%, major morbidity rate was 9.3%, early graft failure rate 8.5% and early amputation rate was 3.8%. 2 year primary patency, primary assisted patency, secondary patency rates and limb salvage were 73.3%, 75.7%, 76.4% and 87.2%. 5 years results were 63.6%, 69.2%, 70.0% and 81.9% respectively.This series revealed exceptionally good results in patients with diabetes mellitus after short vein bypass grafting in concert with earlier studies since 1981. Compared to long femorodistal grafts there was no difference in longterm patency. Bypass grafting in diabetic foot syndrome is still regarded to have a poor prognosis. Just the contrary is the case. This study in concert with former studies revealed distal origin bypass grafting a durable and effective procedure to fight limb loss in diabetic foot syndrome.Distal origin vein bypass grafting is an excellent method just for patients with diabetes. Looking at limb salvage rates over 80 % in 5 years, this procedure should be offered more often suitable patients with diabetic foot syndrome.

Stentgrafts for endovascular treatment of abdominal aortic aneurysms (AAA) have been commercially available since 1994, with now large numbers of implantations all over the world.From 1994-2001, 115 patients were treated with Stentor, Vanguard and Talent stentgrafts in our institution.Late complications of the first- and second-generation stentgrafts as radiologic or surgical interventions to maintain complete exclusion of the aneurysm amounted to 30% with an additional 22% for observed endoleaks and configuration changes of the stentgraft. Third-generation stentgrafts had a lower complication rate of 12.2% for interventions and 18.3% for late endoleaks and graft changes.High costs of the devices, a pretty high late complication rate, and the uncertain maintenance of stentgraft function to prevent aneurysm rupture currently limit the widespread application of this new technology, leaving conventional aneurysmectomy the standard for aneurysm treatment and reserving the endovascular method for selected patients.

Peripheral arterial occlusive disease in the diabetic patients is characterized predominantly by long segmental occlusion of the tibial arteries with patent segments of pedal arteries. Neuropathy and high susceptibility for foot infection explain the dramatically increased risk of major amputation. The pattern of arteriosclerotic disease allows construction of pedal bypasses especially by the use of short autologous vein grafts employing distal origin of the bypass. Indication and performance of the bypass procedure rely on a complete angiographic evaluation of the arterial system of the diseased limb. Besides the dorsalis pedis artery with its major branches as preferentially used recipient vessel, the posterior tibial artery and its plantar branches may be anastomosed. Thus, improved foot perfusion will allow necessary minor amputations with safe wound healing. The use of autologous vein grafts is associated with a high late patency rate of more than 70% and a late limb salvage rate of more than 80%. Pedal artery bypass grafting should routinely be part of the therapeutic strategies in advanced diabetic foot syndrome with critical limb ischemia and impending limb loss.

Inhibition of platelet aggregation with aspirin and anticoagulation with unfractionated heparin can be considered the gold standard treatment of patients with acute coronary syndromes. Replacement of unfractionated heparins by low-molecular weight heparins seem to further improve the cardiovascular risk. Additional treatment with glycoprotein IIb/IIIa receptor blockers led to a further reduction of the clinical event rate, especially in patients undergoing coronary interventions during an acute coronary syndrome (more than 30% relative risk reduction). However, the latter substances did only lead to marginal improvements in the setting of a conservative stabilization of patients with acute coronary syndrome (7% relative risk reduction). On the contrary, the initial treatment with clopidogrel in addition to aspirin and anticoagulation led to a 20% relative risk reduction for an endpoint of death, myocardial infarction and stroke in the CURE trial. The treatment with aspirin, clopidogrel (including loading-dose) for a treatment period of 3-12 months and anticoagulation for 2 days can be considered the new standard of treatment in patients with acute coronary syndromes (unstable angina, non-ST-segment elevation, myocardial infarction). Glycoprotein IIb/IIIa receptor blockers should be used especially during coronary interventions. Antianginal treatment should include nitrates and betablockers. A treatment with statins and ACE-inhibitors should be initiated in the early course of acute coronary syndrome for plaque stabilization.

Pathologic studies have demonstrated that atherosclerosis involves the whole arterial vessel tree. In the Framingham study, cardiovascular risk factors could be defined with different prognostic value for the development of atherosclerosis in various vascular regions. The prognosis of patients with atherosclerosis in coronary, carotid or leg arteries is worse compared to a normal population. Moreover, patients with symptomatic lesions in one vascular bed often have additional asymptomatic atherosclerotic lesions in other vascular regions. Patients with atherosclerosis in multiple vascular regions have a worse prognosis than patients with atherosclerosis in one vascular bed only. In a study of 804 patients, we could show a significantly higher incidence of cardiovascular events (death, myocardial infarction, stroke) in patients with coronary artery disease (CAD) and additional lesions in peripheral arteries (leg, carotid) during a 3.2-year follow-up compared to those with CAD only. Local and systemic inflammatory processes in the arterial vessel wall are considered to play an important role with regard to plaque instability. It has been suggested, that besides the symptomatic atherosclerotic lesion, multiple stable or unstable lesions are present in the whole arterial vessel tree predicting the patient's prognosis. Chronic infections with multiple pathogens ("concept of infectious burden") probably play an important role by triggering these inflammatory processes. Therefore, systemic therapeutic regimes are necessary for the treatment of patients with atherosclerosis. The platelet aggregation inhibitors improve the prognosis of patients with atherosclerosis in all vascular areas. Another important therapeutic regime is the use of statins, which seem to be not only effective in lipid lowering but also in plaque stabilization.