ESVM Guideline on peripheral arterial disease.

Open AccessESVM Guideline on peripheral arterial diseaseUlrich Frank, Sigrid Nikol, Jill Belcha, Vinko Boc, Marianne Brodmann, Patrick H. Carpentier, Ali Chraim, Caitriona Canning, Evangelos Dimakakos, Anders Gottsäter, Christian Heiss, Lucia Mazzolai, Juraj Madaric, Dan Mircea Olinic, Zsolt Pécsvárady, Pavel Poredoš, Isabelle Quéré, Karel Roztocil, Agata Stanek, Dragan Vasic, Adriana Visonà, Jean-Claude Wautrecht, Miroslav Bulvas, Mary-Paula Colgan, Walter Dorigo, Graeme Houston, Thomas Kahan, Holger Lawall, Isak Lindstedt, Guillaume Mahe, Romeo Martini, Giles Pernod, Stanislaw Przywara, Marc Righini, Oliver Schlager, and Piotr TerleckiUlrich Frank PAD Guideline Writing Group Search for more papers by this author, Sigrid Nikol PAD Guideline Writing Group Search for more papers by this author, Jill Belcha PAD Guideline Writing Group afor the European Society of Vascular MedicineSearch for more papers by this author, Vinko Boc ESVM Board Authors Search for more papers by this author, Marianne Brodmann ESVM Board Authors Search for more papers by this author, Patrick H. Carpentier ESVM Board Authors Search for more papers by this author, Ali Chraim ESVM Board Authors Search for more papers by this author, Caitriona Canning ESVM Board Authors Search for more papers by this author, Evangelos Dimakakos ESVM Board Authors Search for more papers by this author, Anders Gottsäter ESVM Board Authors Search for more papers by this author, Christian Heiss ESVM Board Authors Search for more papers by this author, Lucia Mazzolai ESVM Board Authors Search for more papers by this author, Juraj Madaric ESVM Board Authors Search for more papers by this author, Dan Mircea Olinic ESVM Board Authors Search for more papers by this author, Zsolt Pécsvárady ESVM Board Authors Search for more papers by this author, Pavel Poredoš ESVM Board Authors Search for more papers by this author, Isabelle Quéré ESVM Board Authors Search for more papers by this author, Karel Roztocil ESVM Board Authors Search for more papers by this author, Agata Stanek ESVM Board Authors Search for more papers by this author, Dragan Vasic ESVM Board Authors Search for more papers by this author, Adriana Visonà ESVM Board Authors Search for more papers by this author, Jean-Claude Wautrecht ESVM Board Authors Search for more papers by this author, Miroslav Bulvas ESVM Country Society Authors Search for more papers by this author, Mary-Paula Colgan ESVM Country Society Authors Search for more papers by this author, Walter Dorigo ESVM Country Society Authors Search for more papers by this author, Graeme Houston ESVM Country Society Authors Search for more papers by this author, Thomas Kahan ESVM Country Society Authors Search for more papers by this author, Holger Lawall ESVM Country Society Authors Search for more papers by this author, Isak Lindstedt ESVM Country Society Authors Search for more papers by this author, Guillaume Mahe ESVM Country Society Authors Search for more papers by this author, Romeo Martini ESVM Country Society Authors Search for more papers by this author, Giles Pernod ESVM Country Society Authors Search for more papers by this author, Stanislaw Przywara ESVM Country Society Authors Search for more papers by this author, Marc Righini ESVM Country Society Authors Search for more papers by this author, Oliver Schlager ESVM Country Society Authors Search for more papers by this author, and Piotr Terlecki ESVM Country Society Authors Search for more papers by this authorPublished Online:December 02, 2019https://doi.org/10.1024/0301-1526/a000834PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit SectionsMoreESVM Board AuthorsVinko Boc* (Slovenia), Marianne Brodmann (Austria), Patrick H Carpentier (France), Ali Chraim* (Ukraine), Caitriona Canning (Ireland); Evangelos Dimakakos* (Greece), Anders Gottsäter (Sweden), Christian Heiss (Germany), Lucia Mazzolai (Switzerland), Juraj Madaric* (Slovakia), Dan Mircea Olinic* (Romania), Zsolt Pécsvárady* (Hungary), Pavel Poredoš* (Slovenia), Isabelle Quéré (France), Karel Roztocil (ESVM President, Czech Republic), Agata Stanek (Poland), Dragan Vasic* (Serbia), Adriana Visonà (Italy), and Jean-Claude Wautrecht* (Belgium)ESVM Country Society AuthorsMiroslav Bulvas (Czech Republic), Mary-Paula Colgan (Ireland), Walter Dorigo (Italy), Graeme Houston (UK), Thomas Kahan (Sweden), Holger Lawall (Germany), Isak Lindstedt (Sweden), Guillaume Mahe (France), Romeo Martini (Italy), Giles Pernod (France), Stanislaw Przywara (Poland). Marc Righini (Switzerland), Oliver Schlager (Austria), and Piotr Terlecki (Poland)*Indicates ESVM Board members who were also nominated by their Country Society as reviewers.The European Society of Vascular Medicine (ESVM) was founded in Paris in 2012 as a confederation of already existing and emerging European societies of vascular medicine. At the founding congress of the new society in Potsdam, Germany in 2015 the different national societies sent experts to a panel to draft an ESVM Guideline on Peripheral arterial disease (PAD). After reviewing and discussing the already existing national guideline of the different countries, the panel decided to consider the latest German S3 Guideline on PAD from November 2015 [1] as the backbone of the new ESVM PAD Guideline, update where appropriate and supplement with data from rigorous literature searches. Permission from the German Society was given.The ESVM acknowledges the significant and valuable aid from the German Angiology Society and their generosity in allowing their own Guideline to form the basis of this Guideline.Thus, the German S3 guideline [1], which is a national intersociety consensus guideline – with multiple different participating specialties – was translated into English, reviewed and shortened or adapted according to consensus achieved among ESVM experts and some new chapters and new recommendations/statements added.The clear focus of the new ESVM Guideline is – in the spirit of the Society – the medical and endovascular aspects of the diagnosis and therapy of PAD. The aim of the ESVM guideline process was to harmonize and optimise the content and the principal statements between the different national member societies of the ESVM. Thus, a draft of the new guideline was presented to all national European societies for revision and comment prior to finalization. The literature has been reviewed to January 2019.Summary of consensus processFor the German guidelines, a total of 27 medical societies/organisations, two support groups and the German Pension Fund (Deutsche Rentenversicherung Bund) received written invitations to participate in the original guideline. A total of 24 societies/organizations had responded by the end of 2012, altogether signaling their interest in collaboration.For this current ESVM guideline, the 19-member states of the ESVM contributed, with a small writing group taking the lead. All 19 angiology societies were given time to review the new common guideline and formally endorsed its content. The key issues were formulated and agreed upon at consensus meetings and were gradually elaborated by the ESVM PAD guideline working group to harmonize standards of care within the ESVM member countries. Then, the content was further discussed and accredited in final format by the national angiology/vascular medicine societies.Timeline of work•Guideline Committee approval of subject matter, permission from German Society of Angiology to use German Guideline as basis for ESVM Guideline (Rome May 2016)•Allocation of writing group (Rome 2016), translation from German, literature search (May to Nov 2016)•Draft 1: Presentation of draft 1 to Guideline Committee and ESVM Board by nominal group process, (Hamburg November 2nd 2016)•Draft 2: Full day Consensus Meeting (Hamburg November 3rd 2016)•Draft 3: Circulation of draft 3 to ESVM Board taking into account Consensus Meeting comments,•Draft 4: Presentation of draft 4 to ESVM Congress (Prague, March 2018) at a Consensus Meeting,•Draft 5: Circulated to the ESVM Board•Draft 6: Circulated and approved by the ESVM Board, after taking into account further ESVM Board comments, as ready to be shared with Country Societies, by nominal group process (May 2018)•Draft 7: circulated to all Vascular Medicine/Angiology Society representatives/authors for comments (May to Oct 2018).•Draft 8: Circulated to ESVM Board and Society Representatives, considering Society Representatives comments (Oct 2018)•Draft 9: ESVM Board meeting (Frankfurt Oct 2018) by nominal group process•Draft 10: Literature update via ESVM Guideline Committee (Jan 2019)•Draft 11: Incorporation of final comments from all, penultimate draft, circulated to ESVM Board and Country Society Representatives for final approval and sign off (May to June 2019)•Draft 12: Penultimate version circulated to ESVM Board, Guideline Committee and Country Reviewers•Draft 13: Final version circulated as per version 12 and approved1.1 ObjectiveThe objective of the present guideline is to provide evidence-based, comprehensive and optimal care recommendations for patients with atherosclerotic peripheral artery disease (PAD) of the lower limbs. The guideline is meant to aid medical personnel and patients in making decisions regarding the optimal diagnostic and therapeutic measures for patients with PAD, and to aid with action and decision routes, which may be modified in justified cases. Guidelines established by scientific medical societies are not legally binding for physicians and may thus neither cause liability nor release physicians from liability. What legally constitutes a medical standard in the treatment of a given individual can only be determined individually. The present guideline thus does not relieve physicians from their obligation to individually manage their patients by appraising their patients’ overall situation.The present guideline aims to compile the most significant evidence and information on the treatment of peripheral arterial disorders from various specialties to offer the reader reliable assistance in everyday practical clinical life.1.2 Which patients does this guideline refer to?The guideline refers to adults of any age with asymptomatic or symptomatic peripheral arterial circulation disorders due to atherosclerosis. It is also valid for patients at a markedly increased PAD risk, e.g. atherosclerosis patients with coronary artery disease, carotid stenosis, renal impairment, diabetes mellitus or cerebrovascular disease. The guideline covers all areas of epidemiology, diagnostics, treatment and follow-up care for patients with PAD bar the surgical options.The guideline does not apply to children. Treatment strategies for non-atheromatous causes of peripheral artery occlusion processes (vasculitis, dissection, giant-cell arteritis, fibromuscular dysplasia, radiogenic stenoses, and entrapment syndromes) are to be distinguished from atherosclerotic stenoses/occlusions and they are not the focus of the present guideline.1.3 Guideline usersThe guideline is addressed to all concerned with the care and treatment of patients with PAD. The addressees include physicians, and allied health professionals in outpatient/in-patient care and rehabilitation medicine who care or treat patients with PAD. The guideline is also intended to serve as a source of up-to-date information for public-health institutions, and government policy.1.4 Participation of interest groups1.4.1 Organization, financing, and editorial freedomThis Guideline was financed by the ESVM. No monies from Industry were received for the preparation of this guideline. All the current guideline group members disclosed potential conflicts of interest in writing and these are present online in Appendix 1.1.5 Review and selection of scientific documents (evidence-based)National and international guidelines were systematically reviewed in the guideline International Network (http://www.g-i-n.net/) database for national and international guidelines that had been published under the search terms “PAD”, “peripheral arterial disease”, “peripheral artery disease” and “claudication “and “critical limb ischemia”. Importance was attached to the systematic development of, and comprehensible evidence base for, the given recommendations. Secondly, the literature was scanned for further new evidence-based findings that would modify the German guideline including more recent publications to January 2019.1.6 Recommendations and levels of evidenceFor the description of the scientific evidence and the degree of recommendation we adopted our systematology on the recommendations of the European Society of Cardiology and the European Society for Vascular Surgery [2]. Thus, we describe the level of evidence in three categories, from A (best level of evidence based on multiple randomized clinical trials) to C (consensus of opinion of the experts or small studies or registries. Based on these different levels of evidence we formulated our recommendations in the generally accepted way of type I (recommended) to III (not recommended) statements (Table 1.6).Table 1.6 Class of recommendation used in these Guidelines.Class of RecommendationDefinitionProposal(Source: ESC Recommendation for Guideline Production 2010) [2].Class IEvidence and/or general agreement, that a given treatment or procedure is beneficial, useful, effectiveRecommended/indicatedClass IIConflicting evidence and/or divergence of opinion about usefulness/efficacy of the treatment or procedureClass IIaWeight of evidence/opinion in favour of usefulness/efficacyShould be consideredClass IIbUsefulness/efficacy is less well established by evidence/opinionMay be consideredClass IIIEvidence or general agreement that the given treatment or procedure is not useful/effective and in some cases may be harmfulNot recommendedTable 1.6 Class of recommendation used in these Guidelines.View as image HTML Level of evidenceLevel of Evidence AData derived from multiple randomized clinical trials or meta-analysisLevel of Evidence BData derived from single randomized clinical trial or large non-randomized studiesLevel of Evidence CConsensus of opinion of the experts and/or small studies, retrospective studies, registriesView as image HTML 2 Definition and epidemiology2.1 DefinitionPeripheral arterial disease (PAD) affecting the lower limb occurs where there is a blood circulation disorder of the arteries that supply the limbs, which may be partial (due to a stenosis) or complete (due to an occlusion). In approx. 95 % of cases, chronic PAD is caused by atherosclerosis. It is a complex medical condition, which may be asymptomatic in its early stages, although that may affect all arterial vascular regions of the body. In addition to the large peripheral vessels, smaller vessels supplying the skin and muscles are often affected. Acute severe peripheral circulatory disorders are rarer than the chronic form, developing from acute embolic or atherothrombotic vascular obstructions such as plaque rupture. The following guideline recommendations address acute and chronic arterial circulatory disorders in the lower limbs distal to the abdominal aorta.Inflammatory, genetic, and traumatic causes (approx. 5 % of PAD cases) become less frequent with increasing age, while embolic events (cardiac or arterio-arterial) become more frequent [3].Myocardial infarction, stroke, and PAD are different manifestations of atherosclerosis [4]. The most severe form of PAD is tissue death / necrosis with the threat of amputation of the affected limb. This Guideline deals with peripheral arterial disease affecting the lower limb only.In Europe, the Fontaine staging system is applied to clinically classify PAD in terms of symptoms. The Rutherford classification is more conventional in the USA and international science, and distinguishes between 3 grades and 6 categories, which makes the categorization of the severity of the disease more precise. Table 2.1 shows the classification of PAD according to Fontaine stages and Rutherford grades and categories. The clinical stages are indicated with the terms “intermittent claudication” (Fontaine stage II) and/or “critical limb ischemia” (CLI) in later Fontaine stages III and IV.Table 2.1 Classification of PAD according to Fontaine stages and Rutherford grades and categories.RutherfordFontaine StageClinical symptomsGradeCategoryClinical symptomsIAsymptomatic00AsymptomaticII aWalking distance > 200 mI1Mild claudicationII bWalking distance < 200 mI2Moderate claudicationI3Severe claudicationIIIRest painII4Rest painIVIschemic ulcers or gangreneIII5Limited Ischemic ulceration not exceeding ulcer of the digits of the footIII6Severe ischemic ulcers or frank gangreneTable 2.1 Classification of PAD according to Fontaine stages and Rutherford grades and categories.View as image HTML 2.2 Ankle-brachial pressure indexThe prevalence of asymptomatic PAD among the general population can only be estimated by non-invasive methods of investigation. Most frequently this is detected by the ankle-brachial pressure index (ABI) measured by non-invasive Doppler pressure measurement (also see Chapter 3.2, Diagnostics). The cut-off value for the diagnosis of PAD is an ABI value ≤ 0.9. The sensitivity of an ABI value of ≤ 0.9 for the presence of at least a 50 % vascular stenosis (verified by the gold standard angiography) is almost 95 % at rest, with a specificity of nearly 100 % [5].Systematic ABI measurements following stress tests increase the detection and thus the prevalence of PAD by approx. 30 %. An ABI decrease by 15 to 20 % following walking stress – compared with baseline values at rest – is indicative of PAD [6, 7].2.3 Epidemiology2.3.2 Prevalence and incidenceNumerous epidemiological studies based on objective research techniques (usually ABI measurements) have shown an overall 3 to 10 % prevalence of PAD within the population. The prevalence of symptomatic intermittent claudication increases from 3 % among 40-year-old patients to 6 % among those aged 60-65. From age 70 the prevalence is seen to increase to 15 to 20 % [8, 9]. In 2010, the global prevalence of PAD (ABI ≤ 0.9) was mathematically estimated from the data of a systematic review to be worldwide 202 million. Within the EU between 2000 and 2010, the incidence increased by 28.7 % in low- and medium-income countries and by 13.1 % in high-income countries [10].The ratio between patients diagnosed as asymptomatic by ABI and those presenting with symptomatic claudication (who mostly have decreased ABI values) is approx. 4:1 irrespective of age [11].Multisite atherosclerotic artery disease is common and associated with a worse outcome, as reviewed elsewhere [12]. Thus, in people with PAD (ABI < 0.90), CAD was present in 25–70 %, carotid artery stenosis (> 70 %) in 14–19 %, and renal artery stenosis (> 75 %) in 10–23 %. In patients with carotid artery stenosis, PAD was present in 18–22 %, whilst patients with CAD were reported to have PAD in 7–16 % [12]. Compared to people with no PAD, the prevalence of CAD is two- to four-fold higher in PAD patients, and the severity of PAD is associated to the prevalence of CAD. Conversely, left main coronary artery stenosis and multivessel CAD are independent predictors of PAD, and patients with PAD exhibit more advanced coronary atherosclerosis. Accordingly, coexisting PAD in patients with CAD is associated with a worse outcome.Also, cardiac conditions other than CAD are common in PAD patients [12]. Compared to a general population, left ventricular dysfunction is at least two-fold more prevalent in patients with PAD, matched for age and sex. PAD increases the risk for incident heart failure, at least in people with no prevalent CAD. A multivariable-adjusted population-attributable risk for incident heart failure with an ABI < 1.00 was 6 %, compared with 8 % for CAD, 15 % for hypertension, and 14 % for diabetes [13]. Furthermore, the presence of PAD in patients with heart failure independently predicts hospitalizations and death. Patients with PAD have an increased risk for incident atrial fibrillation. Also, the presence of atrial fibrillation in patients with PAD is associated with more severe forms (assessed by the Rutherford classification) and with an increased cardiovascular morbidity and mortality.In the prospective, non-interventional nationwide epidemiological trial on Ankle-Brachial Index (Get-ABI Study), every fifth (21 %) of 6,880 patients aged 65 or older had an ABI of < 0.9 or clinical manifestation of PAD [14]. Investigating 4,814 subjects aged 45 to 75 in the general population, the Heinz Nixdorf Recall Study identified an ABI of < 0.9 in 6.4 % (men) and 5.1 % (women), increasing to 8.2 % and 5.5 % when asymptomatic forms of PAD were additionally taken into consideration [15].The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) Program produced prevalence data of patients at risk (aged ≥ 70 years or 50- to 69- year-old smokers or patients with diabetes) in primary care. In this study, 29 % of the overall population showed a decreased ABI or manifest PAD [16]. In diabetes patients in the POPADAD study over the age of 40 years this was 20 % [17].According to the current literature, however, general screening of asymptomatic patients is not recommended at present, the prevalence among low-risk groups being 1 to 4 % and approximately 17–20 % in mixed-risk populations [17, 18]. Although, asymptomatic patients have a higher than normal risk of cardiovascular events, this guideline does not deal with recommendations for the management of these subjects but focusses on the key area of risk reduction in symptomatic patients.2.3.2.1 Gender prevalenceClaudication is more frequent among men in younger age groups, but there is practically no gender-specific differences in older age groups. Indeed, in the GetABI Study, PAD prevalence was seen to be higher in women than in men after the age of 75 [9]. At the time of diagnosis of PAD, women are older, more frequently obese, have diabetes, and more frequently present with CLI and vascular obstruction; men are more frequently smokers [19, 20].However, preliminary indications suggest a gender-dependent distribution pattern of PAD – with cumulative femoropopliteal and multilevel disease in women and a more frequent infrapopliteal distribution pattern among men – this requires further confirmation in larger-scale study populations [21].2.3.2.2 Prevalence in different ethnic groupsLinks with different ethnic populations such as those of Afro-Caribbean decent (non-Hispanic origins) have been seen to increase the risk of PAD by more than twofold, which cannot be exclusively explained on the basis of an increased presence of other risk factors, such as hypertension and diabetes [22]. These differences in PAD prevalence have recently been corroborated by the Genetic Epidemiology Network of Arteriopathy (GENOA) study [23].2.4 Cross risk of atherothrombotic eventsIn the presence of an atherothrombotic disease in one vascular bed (e.g. PAD), patients are at high risk of cardiovascular morbidity and mortality in other vascular beds. Table 2.2 summarizes the “cross risk” between different atherothrombotic manifestations. PAD patients, having experienced one atheromatous disease, are thus at a clearly increased risk for further cardiovascular events, including myocardial infarction and ischemic stroke.Table 2.2 Cross risk between various atherothrombotic manifestations.Risk compared to overall populationNew eventIn the event of previous MI: Frequency of occurrenceIn the event of previous stroke: Frequency of occurrence*Sudden death = occurrence within 1 hour and usually from coronary artery disease (CAD) cause. [24–27].Ischemic stroke2–3 × including angina and sudden death*9×Myocardial infarction5–7 × including death3–4 × including transient ischemic attackPAD4 × fatal coronary events2–3 × including TIATable 2.2 Cross risk between various atherothrombotic manifestations.View as image HTML 2.4.1 Concomitant PAD and coronary artery disease and/or cardiac failure2.4.1.1 Coronary artery disease (CAD)The occurrence of both PAD and CAD together is frequent and easily overlooked due to a limitation of walking distances by angina pectoris or dyspnea, or vice versa. Such a combination severely worsens prognosis of the patients compared with those with a single manifestation [28].The IPSILON study, a French cross-sectional study in primary care patients, detected PAD in 26.6 % of 1,340 patients with CAD without known manifestation of PAD by means of the ABI [29]. An investigation with simultaneous peripheral and coronary angiography in patients with claudication or CLI identified prevalent CAD (≥ 50 % coronary stenosis in coronary angiography) among 67 of 107 patients (62 %). The presence of diabetes mellitus further increased the likelihood of coincidental CAD and especially coronary multivessel disease in patients with PAD [16, 30]. In patients from the Reduction of Atherothrombosis for Continued Health (REACH) registry, fatal and nonfatal events increased from 13 % in patients with CAD alone to 23.1 % in those with coincidental CAD and PAD after one year of observation [31].2.4.1.2 Heart failureIn a sub-study of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) trial in patients with heart failure with reduced left ventricular systolic function (HFrEF), multivariate analysis showed patients with CLI (637 of 5,011 patients, 12.7 %) to have both an increased mortality risk (HR 1.36; 95 % CI: 1.19–1.56) and an increased risk for fatal and nonfatal MI (time to first event HR 1.67, 95 % CI: 1.24–2.27) compared to patients without concomitant PAD [32]. In addition, cardiac failure impairs peripheral blood circulation due to decreased cardiac output, as well as the patency rates after endovascular interventions.Patients with both disorders are physically less resilient and show less improvement through physical training. This was shown by an investigation within the “Heart Failure: A Controlled Trial Investigating Outcomes of exercise traiNing” (HF-ACTION) in patients with ejection fraction ≤ 35 % and cardiac failure NYHA II to IV. Patients with concomitant PAD (157 of 2,331, 6.8 %) showed less improvement in a structured physical exercise program than patients without concomitant PAD. This disorder was shown to be an independent predictor of mortality or hospitalization (HR 1.31, 95 % CI: 1.06–1.62) [33].Following endovascular intervention, participants with concomitant HFrEF (EF < 40 %) showed poorer primary 1-year patency rates (43.2 % vs. 56.6 %) compared with patients with an EF of > 40 %, and similar differences were seen in secondary patency rates. Finally, limb preservation was poorer in patients with coincidental cardiac failure [34].RecommendationClass of recommendationLevel of evidenceIt is recommended that recognition be given that Patients with PAD have a high risk of vascular events in other vascular beds, and as such these patients should always be considered very high risk for further events.IAIn patients with PAD, it is recommended that optimization of treatment of the concomitant clinical coronary artery disease and cardiac failure should be undertaken.IBView as image HTML 2.4.2 PAD and diabetes mellitusRegardless of type, diabetes mellitus is associated with an increased risk of peripheral atherosclerosis. A systematic review of risk factors for PAD from 34 trials conducted since 1997 estimated the po