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This study investigated the distribution of risk factors, lesion characteristics and endovascular revascularization (EVR) strategies in patients with peripheral arterial disease (PAD) with vs without diabetes mellitus (DM). Data were collected within the RECcording COurses of vasculaR Diseases (RECCORD) registry. Demographic data, lesion localization (iliac vs femoropopliteal vs below-the-knee (BTK)) and lesion complexity score (LCS) based on number of affected segments, and lesion length (< 10 vs 10–20 vs > 20 cm), EVR strategies and peri-procedural complications were analysed in 786 patients with and 1337 without diabetes mellitus. Patients with diabetes mellitus were older (71.6 ± 9.6 vs 69.4 ± 10.5 years, P < .001) and had higher LCS and more often BTK lesions ( P < .05 for all). Lesions were treated less frequently with stents (48.7 vs 59.6%, P < .001) in patients with diabetes mellitus, whereas a non-significant trend was noticed for higher DCB treatment rates (48.3 vs 44.4%, P = .07). Post-interventional ankle-brachial index (ABI) increase was similar (from .77 ± .28 to .92 ± .25 with diabetes mellitus and from .74 ± .21 to .90 ± .20 without diabetes mellitus, P < .001 for both). Peri-/post-procedural complications were low in both groups (4.6%). Patients with diabetes mellitus, who undergo endovascular revascularization are older, have more comorbidities and higher target lesion complexity. However, treatment success rates are similar and complication rates are low.

Peripheral artery occlusive disease is a prevalent but underdiagnosed manifestation in patients with diabetes and also in patients with diabetic foot ulceration. There is insufficient awareness of its clinical manifestations, including intermittent claudication and critical limb ischemia and of its risk of adverse limb outcomes. This review aims to highlight essential elements of the prevalence of peripheral artery disease in patients with diabetes and the the pathway of clinical diagnosis. We report the actual standards and evidence based, interdisciplinary management including conservative, interventional and surgical treatment options and also the needs of follow-up care.

Summary: Background: The RECcording COurses of vasculaR Diseases (RECCORD) registry established by the German Society of Angiology – Society for Vascular Medicine aimed to address the lack in contemporary real-world data regarding current practice of medical and interventional care in vascular patients. We herein report the demographic and procedural characteristics of the first 1000 patients undergoing endovascular revascularization (EVR) for symptomatic peripheral artery disease (PAD). Patients and methods: RECCORD is an observational, prospective, multicenter, all-comers registry. Only patients undergoing EVR for symptomatic PAD are included and followed up for at least 1 year. Demographic characteristics, comorbidities, previous peripheral vascular interventions, medication, clinical stage of lower extremity artery disease (Rutherford category), hemodynamic parameters, and procedural data including complications are recorded via an entirely web-based platform. Results: Of the first 1000 patients (mean age 70 ± 10 years, 35% female) with 1096 EVR at 1477 vascular segments of the lower extremities, 25.0% were at the stage of chronic limb threatening ischemia (CLTI) and 75.0% at non-CLTI. The femoropopliteal segment was the dominant target lesion site (61.0%), followed by iliac (26.4%) and below-the-knee EVR (10.3%). Only angioplasty was performed in 130 EVR (11.9%), adjunctive drug coated balloons (DCB) in 498 (45.4%), additional stenting in 633 (57.8%). Debulking devices were used in 106 (9.7%) EVR. Clinical (Rutherford categories) and hemodynamic parameters (ankle-brachial-index) as well as secondary preventive medication were significantly improved post EVR. Periprocedural complications occurred in 63 (5.7%) EVR with pseudoaneurysm as the leading complication type in 26 (2.4%) EVR. Conclusions: The baseline data of the first 1000 patients from the RECCORD registry representing the real-world setting illustrate that the majority of EVR are performed in patients with claudication. Adjunctive use of DCB and stenting are the dominant types of EVR, while periprocedural complications are at an acceptable low rate.

Bundesweit steigt die Zahl stationar behandelter Patienten mit peripherer arterieller Verschlusskrankheit (PAVK). Dabei nahm der Anteil von Diabetespatienten in den letzten Jahren ebenfalls kontinuierlich zu, er betragt bei kritischer Extremitatenischamie mittlerweile fast 50 %. Die Zahl der hohen Amputationen infolge Durchblutungsstorungen betragt etwa 16.000 pro Jahr, davon werden uber 70 % bei Menschen mit Diabetes mellitus durchgefuhrt. Das Risiko einer hohen Amputation ist fur diese Patienten um das ca. 8-Fache erhoht. Ein wesentlicher Risikofaktor dafur ist die kritische Extremitatenischamie bei PAVK. Trotz aktueller Leitlinienempfehlungen wird gerade bei Diabetespatienten haufig keine bildgebende Diagnostik der PAVK vor Amputationen durchgefuhrt. Multimorbide diabetische Patienten mit kritischer Extremitatenischamie sollen, sofern moglich und bei geeigneter Expertise, zunachst endovaskular revaskularisiert werden. Neue technische Entwicklungen (DES [„drug eluting stent“], DEB [„drug eluting balloon“]) verbessern die Offenheitsraten weiter. Obwohl diese nach endovaskularem Eingriff etwas schlechter sind, ist die hiermit erreichte Beinerhaltungsrate vergleichbar dem Ergebnis nach Bypassanlage. Endovaskulare und offene chirurgische Eingriffe sind keine konkurrierenden Methoden, sondern erganzen sich in spezialisierten Gefaszentren. Diabetespatienten mit fortgeschrittener Niereninsuffizienz und Fusulzerationen haben eine deutliche schlechtere Prognose hinsichtlich technischem Erfolg, Offenheitsrate, Beinerhalt und Uberleben.

Objective: Diabetes is one of the most widespread diseases in Germany. Common complications are diabetic foot ulcers (DFU), which are associated with a cost-intensive treatment and serious adverse events, such as infections, amputations. This cost-effectiveness analysis compares two treatment options for patients with DFU: a TLC-NOSF dressing versus a neutral dressing, assessed through a European double-blind randomised controlled trial (RCT), Explorer. Methods: The evaluation of the clinical outcomes was associated to direct costs (costs for dressings, nursing time, hospitalisation etc.) of both dressings, from the perspective of the statutory health insurance in Germany. Due to the long mean healing time of a DFU, the observation period was extended from 20 to 100 weeks in a Markov model. Results: After 20 weeks, and with complete closure as a primary endpoint, the model revealed direct treatment costs for DFU of €2,864.21 when treated with a TLC-NOSF dressing compared with €2,958.69 with the neutral control dressing (cost-effectiveness: €6,017.25 versus €9,928.49). In the Markov model (100 weeks) the costs for the TLC-NOSF dressing were €5,882.87 compared with €8,449.39 with the neutral dressing (cost-effectiveness: €6,277.58 versus €10,375.56). The robustness of results was underlined by several sensitivity analyses for varying assumptions. The frequency of weekly dressing changes had the most significant influence in terms of parameter uncertainty. Conclusion: Overall, the treatment of DFU with a TLC-NOSF dressing is supported from a health economic perspective, because both the treatment costs and the cost-effectiveness were superior compared with the neutral wound dressing.

Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1β (IL-1β) may play an important pro-inflammatory role in the pathogenesis of this disease. Interruption of IL-1β signaling was hypothesized to decrease plaque progression in the leg macrovasculature and improve the mobility of patients with PAD with intermittent claudication. Thirty-eight patients (mean age 65 years; 71% male) with symptomatic PAD (confirmed by ankle–brachial index) were randomized 1:1 to receive canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. The mean vessel wall area (by 3.0 T black-blood magnetic resonance imaging (MRI)) of the superficial femoral artery (SFA) was used to measure plaque volume. Mobility was assessed using the 6-minute walk test. Canakinumab was safe and well tolerated. Markers of systemic inflammation (interleukin-6 and high-sensitivity C-reactive protein) fell as early as 1 month after treatment. MRI (32 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA in either placebo-treated or canakinumab-treated patients. Although an exploratory endpoint, placebo-adjusted maximum and pain-free walking distance (58 m) improved as early as 3 months after treatment with canakinumab when compared with placebo. Although canakinumab did not alter plaque progression in the SFA, there is an early signal that it may improve maximum and pain-free walking distance in patients with symptomatic PAD. Larger studies aimed at this endpoint will be required to definitively demonstrate this. ClinicalTrials.gov Identifier: NCT01731990

ZusammenfassungDie 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.

Prior studies have observed an association between the burden of atherosclerotic vascular disease and the risk of venous thromboembolism (VTE). The association is not well described in peripheral artery disease (PAD) after lower extremity revascularization (LER).To describe the risk of, factors associated with, and outcomes after VTE, as well as the association of low-dose rivaroxaban plus antiplatelet therapy with VTE after LER.This global, multicenter cohort study used data from the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD) randomized clinical trial, which enrolled patients from 2015 to 2018 with median follow-up of 28 months. Participants included patients with PAD undergoing LER. Patients with an indication for therapeutic anticoagulation were excluded. Data were analyzed from September 2020 to September 2021.Randomization to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily; short-term clopidogrel was used at the discretion of the treating physician.Symptomatic VTE was a prespecified secondary outcome and prospectively collected.Among 6564 patients (median [IQR] age, 67 [61-73] years; 4860 [74.0%] men), 66 patients had at least 1 VTE. The 3-year rate of VTE in patients receiving placebo was 1.7%, and the pattern of risk was linear (year 1: 0.5%; year 2: 1.1%). After multivariable modeling, weight (hazard ratio [HR], 3.04; 95% CI, 1.09-8.43), hypertension (HR, 2.11; 95% CI, 0.91-4.89), prior amputation (HR, 2.07; 95% CI, 0.95-4.53), and older age (HR, 1.81; 95% CI, 1.06-3.11) were associated with increased risk of VTE. VTE was associated with risk of subsequent mortality (HR, 7.22; 95% CI, 4.66-11.19). Compared with aspirin alone, rivaroxaban plus aspirin was associated with lower VTE risk (HR, 0.61; 95% CI, 0.37-0.998; P = .047), with benefit apparent early and sustained over time. This association was not modified by use of clopidogrel at randomization (without clopidogrel: HR, 0.55; 95% CI, 0.29-1.07; with clopidogrel: HR, 0.69; 95% CI, 0.32-1.48; P for interaction = .67).In this cohort study, there was continuous risk for VTE after LER in patients with PAD, with greater risk in patients who were older and had obesity and those with more severe PAD, as reflected by prior amputation. Low-dose rivaroxaban plus aspirin was associated with lower VTE risk compared with aspirin alone, with benefits apparent early and continued over time. The spectrum of venous and arterial thrombotic events and overall benefits of more potent antithrombotic strategies for prevention should be considered after LER for PAD.

ZusammenfassungDie 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

Abstract. The prevalence of peripheral artery disease (PAD) is increasing worldwide and is strongly age-related, affecting about 20 % of Germans over 70 years of age. Recent advances in endovascular and surgical techniques as well as clinical study results on comparative treatment methods strengthened the need for a comprehensive review of the published evidence for diagnosis, management, and prevention of PAD. The interdisciplinary guideline exclusively covers distal aorta and atherosclerotic lower extremity artery disease. A systematic literature review and formal consensus finding process, including delegated members of 22 medical societies and two patient self-support organisations were conducted and supervised by the Association of Scientific Medical Societies in Germany, AWMF. Three levels of recommendation were defined, A = „is recommended/indicated”, B = „should be considered”, C = “may be considered”, means agreement of expert opinions due to lack of evidence. Altogether 294 articles, including 34 systematic reviews and 98 RCTs have been analysed. The key diagnostic tools and treatment basics have been defined. In patients with intermittent claudication endovascular and/or surgical techniques are treatment options depending on appropriate individual morphology and patient preference. In critical limb ischaemia, revascularisation without delay by means of the most appropriate technique is key. If possible and reasonable, endovascular procedures should be applied first. The TASC classification is no longer recommended as the base of therapeutic decision process due to advances in endovascular techniques and new crural therapeutic options. Limited new data on rehabilitation and follow-up therapies have been integrated. The article summarises major new aspects of PAD treatment from the updated German Guidelines for Diagnosis and Treatment of PAD. Limited scientific evidence still calls for randomised clinical trials to close the present gap of evidence.

Objective Treatment of peripheral artery disease (PAD), Fontaine Stage IIb with vasoactive substances is of limited efficacy and does not last beyond the active treatment. Glyceryl trinitrate (GTN) is a vasodilating agent that relaxes vascular smooth muscle cells. The aim was to prove the concept that GTN sublingual powder has sustained clinical efficacy and adequate safety in these patients. Methods This was a multicentre, randomised, double blind, placebo controlled, forced titration, proof of concept study (phase IIa). Patients had a treadmill test at baseline, after 12 weeks of GTN/placebo administration, and at 19 and 26 weeks (without treatment). Primary objectives were an increase in initial claudication distance (ICD) and absolute claudication distance (ACD) at 12 weeks. Results Ninety-five patients were screened and 73 randomised, of which 53 patients completed the 12 week treatment phase (GTN 26, placebo 27). At a baseline ICD of 59.2 ± 32.8 m (GTN) and 57.5 ± 39.7 m (placebo), GTN led to a placebo corrected ICD increase of 23.2% vs. baseline (p = .35). Baseline ACD was 105.3 ± 52.9 m (GTN) and 106.1 ± 95.0 m (placebo), and GTN led to a placebo corrected increase of 3.6% (p = .44), with substantial interindividual variation. The change in claudication distance was greater in patients with an ICD of ≥50 m at baseline (ΔICD 29.3%; p = .19), and an ACD ≥ 100 m (ΔACD 8.5%; p = .40). The effect lasted beyond the active treatment period as shown by a 49.3% increase in ICD (p = .31) and a 20.6% increase in ACD (p = .21) by week 26. GTN sublingual powder was well tolerated. Conclusion Intermittent treatment with nitroglycerin sublingual powder may represent a potential treatment option for patients with PAD stage Fontaine IIb, with an immediate and a sustained effect. The observed increases in ACD and ICD were however not statistically significant in this phase IIa proof of concept study. Further studies are required.

Bundesweit steigt die Zahl stationar behandelter Patienten mit peripherer arterieller Verschlusskrankheit (PAVK). Dabei betragt der Anteil der Diabetiker mit kritischer Extremitatenischamie mittlerweile fast 50 %. Demzufolge werden auch von den jahrlich durchgefuhrten rund 16 000 hohen Amputationen infolge von Durchblutungsstorungen uber 70 % bei Menschen mit Diabetes mellitus durchgefuhrt. Als nichtinvasive hamodynamische Funktionsuntersuchungen werden Knochel- und Zehendruckmessungen, die Doppler-Pulskurvenanalyse, die Duplexsonografie und die transkutane Sauerstoffdruckmessung empfohlen und ermoglichen zusammen mit der bildgebenden Diagnostik die richtige Diagnose. Multimorbide diabetische Patienten mit kritischer Extremitatenischamie sollen, sofern moglich und bei geeigneter Expertise, zunachst endovaskular revaskularisiert werden. Trotz einer etwas schlechteren Offenheitsrate ist die Beinerhaltungsrate dem Ergebnis nach einer Bypassanlage vergleichbar.

The prevalence of diabetes mellitus (DM) and its associated complications such as peripheral artery disease (PAD) and diabetic foot syndrome (DFS) are increasing worldwide. We aimed to determine the contemporary acute and long-term outcome of patients with PAD and DFS in Germany.Nationwide, anonymized data of 40,335 patients hospitalized for PAD and/or DFS from the years 2009-2011 were analyzed and followed up until 2013. Patients were classified into 3 groups: DFS, PAD+DM and PAD without DM. In-hospital and long-term outcome (1156days, 95% CI 1.151-1.161) regarding major and minor amputation and mortality was assessed. Cumulative amputation-free survival and overall survival rates were calculated using Kaplan-Meier analysis.The proportion of DFS, PAD+DM and PAD only was 17.3%, 21.5% and 61.2%, respectively. At index-hospitalization, DFS patients had the highest amputation (31.9% vs. 11.1% vs. 6.0%), yet the lowest revascularization rate (18.2% vs. 67.8% vs. 71.6%) compared to patients with PAD only and PAD+DM (P0.001). Cumulative 4-year survival (57.4%, 60.8% and 70.0%) and amputation-free-survival (45.4%, 74.4% and 86.5%) were lowest for DFS followed by PAD+DM and PAD only (P0.001).Patients with diabetes, particularly those with DFS, have persistent high rates of limb amputation and of mortality in a real-world setting. Our data emphasize the need for further dedicated research to identify and target the underlying causes of the extraordinary poor outcome in this high risk population.

Die periphere arterielle Verschlusskrankheit (PAVK) ist bei Diabetikern eine haufige Komplikation. Doch gerade bei diesen Patienten kann die klinische Stadieneinteilung trugerisch sein. Die wesentlichen Schritte von der Diagnostik und Therapie bis hin zur Nachsorge erfahren Sie in der folgenden Ubersicht.

Die Haufigkeit der PAVK nimmt weltweit zu und auch in der Bundesrepublik steigt die Zahl der stationar behandelten Patienten kontinuierlich an. Die Knochel- und Zehendruckmessungen mit Bestimmung des ABI bzw. TBI sind zuverlassige Methoden zur Diagnostik. Klinisch relevante Begleiterkrankungen sind die KHK, Herz- und chronische Niereninsuffizienz, und der Diabetes mellitus. Patienten mit asymptomatischer und symptomatischer PAVK haben eine deutlich erhohte Morbiditat und Mortalitat.

ObjectivesThe aim of the DiaFu study was to evaluate effectiveness and safety of negative pressure wound therapy (NPWT) in patients with diabetic foot wounds in clinical practice.DesignIn this controlled clinical superiority trial with blinded outcome assessment patients were randomised in a 1:1 ratio stratified by study site and ulcer severity grade using a web-based-tool.SettingThis German national study was conducted in 40 surgical and internal medicine inpatient and outpatient facilities specialised in diabetes foot care.Participants368 patients were randomised and 345 participants were included in the modified intention-to-treat (ITT) population. Adult patients suffering from a diabetic foot ulcer at least for 4 weeks and without contraindication for NPWT were allowed to be included.InterventionsNPWT was compared with standard moist wound care (SMWC) according to local standards and guidelines.Primary and secondary outcome measuresPrimary outcome was wound closure within 16 weeks. Secondary outcomes were wound-related and treatment-related adverse events (AEs), amputations, time until optimal wound bed preparation, wound size and wound tissue composition, pain and quality of life (QoL) within 16 weeks, and recurrences and wound closure within 6 months.ResultsIn the ITT population, neither the wound closure rate (difference: n=4 (2.5% (95% CI−4.7% – 9.7%); p=0.53)) nor the time to wound closure (p=0.244) was significantly different between the treatment arms. 191 participants (NPWT 127; SMWC 64) had missing endpoint documentations, premature therapy ends or unauthorised treatment changes. 96 participants in the NPWT arm and 72 participants in the SMWC arm had at least one AE (p=0.007), but only 16 AEs were related to NPWT.ConclusionsNPWT was not superior to SMWC in diabetic foot wounds in German clinical practice. Overall, wound closure rate was low. Documentation deficits and deviations from treatment guidelines negatively impacted the outcome wound closure.Trial registration numbersNCT01480362and DRKS00003347.

Die Zahl von Majoramputationen ist trotz leicht sinkender Tendenz immer noch erschreckend hoch. Uberwiegend sind Diabetiker von Amputationen betroffen. Ziel muss es sein, die Zahl der Minor- und Majoramputationen zu verringern. Ein Instrument dazu ist das Einholen einer Zweitmeinung in einem Gefaszentrum zur Klarung einer moglichen Revaskularisation und die Schaffung eines landes- und bundesweiten Amputationsregisters.

Die periphere arterielle Verschlusserkrankung (PAVK) ist eine Manifestation der haufig generalisiert auftretenden Atheromatose und nimmt mit steigendem Lebensalter zu. In Deutschland betragt die Pravalenz bei alteren Menschen etwa 20%. Vielfach ist die Erkrankung asymptomatisch, bei etwa 7% der betroffenen Patienten liegt eine Claudicatio intermittens vor, und etwa 0,5–1% der Patienten haben eine kritische Extremitatenischamie. Mit schlechterem klinischen Stadium und schlechterer peripherer Durchblutung steigen Morbiditat und Mortalitat der Patienten mit PAVK. Die Diagnostik basiert auf der Anamnese, der klinischen Untersuchung, der Knochel- oder Zehendruckmessung. Als bildgebende Verfahren kommen in folgender Reihe die farbkodierte Duplexsonografie und bei klinischer Konsequenz die MR-Angiografie und die digitale Subtraktionsangiografie, ggfs. in Interventionsbereitschaft zum Einsatz.

Abstract. Background: The prevalence of peripheral artery disease (PAD) is increasing worldwide. Revascularization procedures constitute a cornerstone of the therapy in PAD, not only in critical limb ischaemia but increasingly also in patients with intermittent claudication. The German Society of Angiology – Society for Vascular Medicine is establishing a nationwide, prospective, multicentre registry to address the lack of contemporary real life data regarding current practice of medical and interventional care in vascular patients and its subsequent long-term outcome. Patients and methods: The RECording COurses of vasculaR Diseases registry (RECCORD registry) is an observational, prospective, multicentre, all-comers registry platform. In the initial phase, patients referred for endovascular revascularization of PAD of the lower limbs will be prospectively included and followed up for at least one year. At baseline, data on patients’ demographic characteristics, comorbidities, previous peripheral interventions, medication, and clinical stage of PAD (Rutherford category), haemodynamic parameters, and procedural data including complications will be assessed. Major adverse cardiac and limb events will be recorded at planned (at six and 12 months) and at any unplanned visits. The therapeutic management will be exclusively left to the discretion of the vascular specialists. Results and conclusions: The RECCORD registry will provide a comprehensive dataset depicting the current real life practice and outcome of vascular care. The seven predefined quality indicators will be used for benchmarking the participating centres. Moreover, identifying factors promoting a favourable outcome might pave the way for an evidence-based therapeutic strategy and a dedicated therapeutic pathway for patients with PAD including patient-oriented best interventional approaches. In the future, the RECCORD registry may provide a general platform to study the courses of various defined vascular diseases in order to get detailed insights into the real life current practice of health care provided to vascular patients.

Background: Peripheral artery disease (PAD) affects 8.5 million people in the US. PAD patients are at high risk for cardiovascular events, and their quality of life is often significantly impaired by decreased mobility. Interleukin-1β (IL-1β) may play an important role in this disease by promoting inflammatory responses that drive atherosclerotic plaque progression and impair vascular function. We sought to test whether interruption of IL-1β signaling would improve patient mobility and decrease plaque progression in the lower extremities. Methods: 38 patients (mean age 65; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive Canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. Plaque volume in the superficial femoral artery (SFA) was assessed serially using 3.0T MRI. Mobility was assessed serially using the 6-minute walk test (maximum and pain-free walking distance). Results: Canakinumab was safe and well-tolerated. 12 patients discontinued (8 placebo, 4 Canakinumab). MRI data (from 31 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA at either time point in placebo-treated patients; nor was there a change in plaque volume in the Canakinumab-treated group. There was a serial and significant improvement in placebo-adjusted maximum and pain-free walking distance observed as early as 3 months after treatment with Canakinumab (58-meter improvement over placebo in pain-free distance at 3 months, P=0.01). Two placebo-treated patients required peripheral vascular interventions due to progression of disease; however, no Canakinumab-treated patients required revascularization during the study. Canakinumab decreased markers of systemic inflammation (IL-6 and hsCRP). Conclusions: Treatment with Canakinumab may improve maximum and pain-free walk distance in patients with symptomatic PAD. In conjunction with results soon to be reported for the CANTOS trial of Canakinumab for secondary prevention of cardiovascular events, additional studies may provide support that inhibition of IL-1β signaling can improve symptoms and function in this patient population with high unmet need.

Die Behandlung von amputationsbedrohten Patienten mit kritischer Extremitatenischamie durch autologe mononukleare Knochenmarkzelltransplantation ist ein moglicher neuer Therapieansatz zur Verbesserung der Durchblutung bei der peripheren arteriellen Verschlusserkrankung (pAVK). Viele Ergebnisse der uberwiegend unkontrollierten klinischen Untersuchungen deuten auf positive Effekte hin. In ersten kleinen randomisierten Untersuchungen bei Patienten mit kritischer Extremitatenischamie konnte nach mononuklearer Stammzelltransplantation kurzfristig eine Reduktion der Amputationsrate beobachtet werden. Zum Wirkmechanismus und zur bestmoglichen Art der Prozedur sind allerdings noch viele Fragen offen und die Bestatigung der ersten Ergebnisse durch grose randomisierte Studien steht noch aus.

Background In peripheral arterial occlusive disease (PAOD), arterial stenosis or occlusion impairs perfusion in the territory of the distal portion of the aorta and the iliac and leg arteries. In Germany, the prevalence of PAOD rises with age, reaching 20% among persons over age 70. Methods This guideline was prepared by a collaboration of 22 medical specialty societies and two patient self-help organizations on the basis of pertinent publications that were retrieved by a systematic search in PubMed for articles that appeared from 2008 to April 2014, with a subsequent update to May 2015. Results 294 articles were assessed, including 34 systematic reviews and 98 randomized controlled trials (RCTs). The diagnostic assessment of PAOD is based on physical examination, blood pressure at the ankles, and color-coded duplex ultrasonography (grade A recommendation). Other tomographic imaging methods can be used for suitable indications. The main elements of the treatment of PAOD are the control of cardiovascular risk factors and structured vascular exercise (grade A recommendation). Acetylsalicylic acid and statins are the main drugs for symptomatic PAOD (grade A recommendation). Patients with claudication and correlated structural findings can undergo an endo - vascular or open surgical procedure. Critical ischemia is an indication for arterial revascularization as soon as possible (grade A recommendation); this may be performed either by open surgery or by an endovascular procedure of one of the types that are now undergoing rapid development, or one of the crural treatment options. There is inadequate evidence concerning the optimal drug regimen after revascularization procedures. Conclusion The diagnostic assessment of PAOD is based on physical examination, measurement of the ankle-brachial index (ABI), and duplex ultrasonography. Acetylsalicylic acid and statins are indicated for patients with symptomatic PAOD. Endovascular procedures should be used if indicated. Randomized studies are needed to provide better evidence on many open questions in the treatment of PAOD.

Critical limb ischemia (CLI) is the terminal stage of peripheral artery disease. Research in recent years has been largely focussed on treatment options such as bypass surgery / endovascular treatment, surgery / primary amputation and additional benefits of supportive pharmacotherapy. Despite this plethora of treatment options, however, patients continue to have a reduced health related quality of life (HRQoL). Aim of the present work was to review the available evidence of improvement of HRQoL with regard to different treatment options. We found that a number of clinical studies have been conducted using HRQoL measures mostly as secondary outcomes in patients with CLI and other less severe forms of peripheral arterial disease. The studies demonstrate a consistent improvement of HRQoL over baseline within the first few months after the intervention. Prostaglandins, but no other pharmacotherapies, appear to be effective in patients without an option for revascularization. Due to a largely differing patient population under investigation and the different degrees of disease progression it appears difficult however to compare different treatment options with respect to their impact on HRQoL. HRQoL improvement as a predefined endpoint of novel therapeutic approach studies should be considered more consequently.

Der Beitrag stellt die wesentlichsten Aspekte der neuen S3-Leitlinie zur Diagnostik und Therapie der peripheren arteriellen Verschlusskrankheit (PAVK) dar 1 . Diese betreffen die Definition und Epidemiologie der PAVK, die Diagnostik mittels klinisch-angiologischer Methoden, apparativer angiologischer sowie bildgebender Verfahren, die Therapie mittels konservativer, interventioneller und chirurgischer Methoden sowie die Nachsorge der Patienten. In Kernaussagen werden Empfehlungen gegeben, deren Empfehlungsgrad von der wissenschaftlichen Evidenz, d. h. von den Ergebnissen klinisch-wissenschaftlicher Studien und anderer Literaturberichte abgeleitet wurde.

Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic syndrome associated with significant morbidity and mortality. PAD is most commonly caused by atherosclerosis obliterans (ASO) and thromboangiitis obliterans (TAO), and can lead to claudication and critical limb ischemia (CLI), often resulting in a need for major amputation and subsequent death. Standard treatment for such severe cases of PAD is surgical or endovascular revascularization. However, up to 30% of patients are not candidates for such interventions, due to high operative risk or unfavorable vascular involvement. Therefore, new strategies are needed to offer these patients a viable therapeutic option. Bone-marrow derived stem and progenitor cells have been identified as a potential new therapeutic option to induce angiogenesis. These findings prompted clinical researchers to explore the feasibility of cell therapies in patients with peripheral and coronary artery disease in several small trials. Clinical benefits were reported from these trials including improvement of ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcO2), reduction of pain, and decreased need for amputation. Nonetheless, large randomized, placebo-controlled, double-blind studies are necessary and currently ongoing to provide stronger safety and efficacy data on cell therapy. Current literature is supportive of intramuscular bone marrow cell administration as a relatively safe, feasible, and possibly effective therapy for patients with PAD who are not subjects for conventional revascularization.Clinical RelevanceThis article describes the background and first results of stem and progenitor cell therapy in patients with critical limb ischemia not suitable for revascularization. The principle as far as it is understood and the methods are described. Compelling evidence suggests that progenitor cell therapy might become a useful adjunct to the treatment options at present. Due to poor prognosis and the increasing number of patients, there is a need for new therapeutic methods. The article gives an overview of first encouraging results provided by early-phase clinical trials. Challenges in this new therapeutic option still include open questions such as cell phenotype, processing, dosing, route of optimal delivery, and frequency of application. Validation by more rigorous controlled trials involving homogenous patient populations are required to confirm the first hopeful results.

SummaryThe degree of thromboprophylaxis in medical outpatients is low despite a substantial risk for venous thromboembolism (VTE). This may be attributable to difficulties in assessing risk. Assessment tools like the Haas’ scorecard aid in determining the need for thromboprophylaxis. We aimed at evaluating how the use of this tool may aid physicians in appropriately using anticoagulants. This was an epidemiological, cross-sectional survey of acute medically ill patients with limited mobility treated by general practitioners and internists. Risk assessment for VTE by the treating physician was compared to calculated risk. Of 8,123 patients evaluated between August 2006 and April 2008, 7,271 fulfilled the in- and exclusion criteria. Mean age was 69.4 ± 13.6 years, and 45.2% were male. Of these 82.8% were high risk based on their acute medical condition, 37.9% based on their underlying chronic condition. Immobilisation, heart failure, pneumonia, age, obesity, and major varicosis were the most frequently encountered risk factors. The agreement between the Haas’ scorecard and physician indicated risk was high. At least 94.1% of patients with high risk received adequate anticoagulation mostly as low molecular weight heparins for a mean duration of 15.1 ± 30.5 days. There is a substantial risk for VTE in medical out-patients. Using a simple structured scorecard resulted in an overall appropriate risk assessment and high degree of anticoagulation. The scorecard may provide a tool to improve the overall awareness for VTE risk in medical outpatients, substantially improving the degree of prophylaxis in a patient population with largely underestimated risk.