Peripheral arterial occlusive disease

Summary

Peripheral arterial disease (PAD) is a disorder affecting all extra-cardiac and extra-cranial arterial territories. The interest in detection and the dedicated local treatment options for PAD patients have increased substantially over the recent years.

PAD is a strong indicator of the presence of systemic atherosclerosis and is associated with a significantly increased risk of myocardial infarction, stroke and death.

The management of patients with PAD should be planned in the context of their natural history, risk factors predicting deterioration and clinical presentation. Treatment options include secondary preventive measures, conservative therapy and surgical, as well as endovascular, revascularisation.

A continuing shift away from surgical revascularisation towards less invasive endovascular procedures for PAD patients is a current trend. Endovascular interventions have greatly changed the therapeutic landscape and are today considered the first-line revascularisation approach for most PAD patients.

Introduction

Peripheral arterial disease (PAD) is a disorder of all arterial beds except for the coronary and intracranial circulation. In routine clinical practice, lower limb arteries are most frequently affected. The interest in PAD detection, medical treatment options and strategies facilitating arterial revascularisation has increased substantially over years. Moreover, rapidly evolving technical innovations have brought about a continuing shift away from surgical revascularisation towards less invasive endovascular procedures [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines., 22. Rogers JH, Laird JR. Overview of new technologies for lower extremity revascularization. Circulation. 2007; 116:2072-85. ].

EPIDEMIOLOGY, RISK FACTORS AND CLINICAL PROGNOSIS

Early epidemiological studies have indicated that total disease prevalence based on objective testing ranges from 3% to 10%, increasing to 15% to 20% in persons over the age of 70 [33. Criqui MH, Fronek A, Barret-Connor EK, Klauber MR, Gabriel S, Goodman D. The prevalence of peripheral arterial disease in a defined population. Circulation. 1985;71:510-5. , 44. Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. Circulation. 1995;91:1472-9. ]. In a large German cross-sectional population study, PAD, as defined by an ankle-brachial index (ABI) <0.9, was shown to be present in 19.8% of men and 16.8% of women above the age of 65 in primary care [55. Diehm C, Schuster A, Allenberg JR, Darius H, Haberl R, Lange S, Pittrow D, von Stritzky B, Tepohl G, Trampisch HJ. High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: cross-sectional study. Atherosclerosis. 2004;172:95-105.
Key article on current epidemiology of PAD.]. Moreover, the presence of PAD was identified as an independent predictor of increased mortality and cardiovascular events out to 5 years in that study [66. Meves S, Diehm C, Berger K, Pittrow D, Trampisch HJ, Burghaus I, Tepohl G, Allenberg JR, Endres HG, Schwertfeger M, Darius H, Haberl R. Peripheral arterial disease as an independent predictor for excess stroke morbidity and mortality in primary-care patients: 5-year results of the getABI study. Cerebrovasc Dis. 2010;29:546-54. ].

Non-modifiable risk factors for PAD of atherosclerotic origin are advanced age and male gender [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.]. Cigarette smoking is the most important modifiable risk factor which impacts on both the risk of development and the progression of disease [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines., 77. Fowkes FG, Housley E, Riemersma RA, et a. Smoking, lipids, glucose intolerance and blood pressure as risk factor for peripheral atherosclerosis compared with ischemic heart disease in the Edinburgh Artery Study. Am J Epidemiol. 1992;135:331-40. ]. PAD is diagnosed one decade earlier in smokers than in non-smokers and amputation is more common in heavy smokers. Whilst diabetes mellitus is associated with a 1.5-fold to 6-fold increase in PAD prevalence, the incidence of amputation is increased 10-fold in diabetics [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.]. Arterial hypertension is associated with a 2.5-fold increase in PAD incidence in men and a 3.9-fold increase in women [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.]. Dyslipidaemia is a further independent risk factor for the development and progression of disease [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.]. In the Framingham study, a fasting cholesterol level >7 mmol/L (270 mg/dL) was associated with a 2-fold increase in the incidence of IC [88. Kannel WB, Skinner JJ Jr, Schwartz MJ, Shurtleff D. Intermittent claudication. Incidence in the Framingham Study. Circulation. 1970;41:875-83. ]. The prevalence of hyperhomocysteinaemia is high in the population with arterial diseases compared with 1% in the general population. Consequently it may be an independent risk factor for atherosclerosis and it may be a stronger risk factor for PAD than for CAD [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.].

It is of note that the distribution pattern of lower limb PAD is affected by the presence of cardiovascular risk factors [99. Diehm N, Shang A, Silvestro A, Do DD, Dick F, Schmidli J, Mahler F, Baumgartner I. Association of Cardiovascular Risk Factors with Pattern of Lower Limb Atherosclerosis in 2659 Patients Undergoing Angioplasty. Eur J Vasc Endovasc Surg. 2006;31:59-63. ]. Iliac disease is associated with younger age, male gender and cigarette smoking, whereas infra-geniculate disease is associated with older age, male gender and diabetes mellitus [99. Diehm N, Shang A, Silvestro A, Do DD, Dick F, Schmidli J, Mahler F, Baumgartner I. Association of Cardiovascular Risk Factors with Pattern of Lower Limb Atherosclerosis in 2659 Patients Undergoing Angioplasty. Eur J Vasc Endovasc Surg. 2006;31:59-63. ].

Besides the local symptoms of lower limb ischaemia which may range from claudication to ischaemic rest pain and tissue loss, atherosclerotic vascular disease may present as a diffuse progressive condition simultaneously affecting multiple arterial beds. Its main clinical manifestations are coronary heart disease, cerebrovascular disease and PAD, which, taken together, have been the leading causes of death in adults in the Western world for many years [1010. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O’Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117:e25-146. ]. During recent years, our understanding of PAD has undergone a profound change. Besides its direct clinical implications related to lower limb ischaemia, PAD is now perceived as an indicator of the presence of generalised atherothrombosis [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.]. Concomitant coronary heart disease and CVD have been diagnosed in up to 90% of patients (and in about 50% of PAD patients) [1111. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. J Am Coll Cardiol. 2006; 47:1239-312.
Most updated version of the AHA guidelines.]. Thus the presence of PAD should be understood as an indication of systemic disease.

Intermittent claudication (IC) and critical limb ischaemia (CLI) are differentiated from a symptomatic and prognostic standpoint. The natural course of IC in lower limbs is comparatively benign. In the Basle study, a large population-based trial, a significant angiographic progression was observed in 63% of PAD patients after 5 years, although 66% did not exhibit disabling or lifestyle-limiting claudication [1212. Da Silva A, Widmer LK, Ziegler HW, Nissen C, Schweizer W. The Basle longitudinal study: report on the relation of initial glucose level to baseline ECG abnormalities, peripheral artery disease, and subsequent mortality. J Chronic Dis. 1979;32:797-803. ]. Only every fourth claudicant deteriorates clinically and ultimately requires revascularisation, whereas a total of 5% of claudicants progress to CLI [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.]. Major amputation is required in only 1% to 3% of claudicants over a 5-year period [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.]. Independent predictors of disease progression are multi-level atherosclerotic disease involvement of lower limb arteries, low ABI, renal insufficiency, diabetes mellitus and heavy cigarette smoking. In contrast to outcomes in claudicants, the presence of CLI is associated with excessive morbidity and mortality rates. One-year mortality and amputation rates of 54% and 46%, respectively, for CLI patients not undergoing arterial reconstruction for various reasons has been reported [1313. Lepantalo M, Matzke S. Outcome of unreconstructed chronic critical leg ischaemia. Eur J Vasc Endovasc Surg. 1996;11:153-7. ]. Another group has experienced a cumulative 1-year mortality rate of 30.4% in CLI patients partly amenable to endovascular or surgical revascularisation [1414. Dick F, Diehm N, Galimanis A, Husmann M, Schmidli J, Baumgartner I. Surgical or endovascular revascularization in patients with critical limb ischaemiaischemia: influence of diabetes mellitus on clinical outcome. J Vasc Surg. 2007;45:751-61.
Interesting article describing interdisciplinary experiences in CLI patients.]. In that series, age and renal insufficiency were independent predictors of higher mortality, whereas arterial revascularisation was independently associated with lower mortality [1414. Dick F, Diehm N, Galimanis A, Husmann M, Schmidli J, Baumgartner I. Surgical or endovascular revascularization in patients with critical limb ischaemiaischemia: influence of diabetes mellitus on clinical outcome. J Vasc Surg. 2007;45:751-61.
Interesting article describing interdisciplinary experiences in CLI patients.].

DIAGNOSTIC STRATEGY

Physical examination of PAD patients should include the entire cardiovascular system including bilateral measurement of upper extremity blood pressures (the higher blood pressure counts since arterial obstructions of upper extremities might be present), assessment of cardiac murmurs, gallops and arrhythmias, examination of carotid, aortic, iliac and femoral bruits as well as palpation for abdominal aortic aneurysm [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.]. Moreover, changes in lower limb skin colour and temperature, muscular atrophy, decreased hair growth and the presence of hypertrophied, slow-growing nails as well as skin lesions should be scrutinised.

The diagnosis of intermittent claudication should include patient history and physical examination with differential diagnosis comprising spinal stenosis (typical patient history contains exertional pain during descending), hip, foot and ankle arthritis, Baker`s cyst, venous claudication and nerve root compression.

Specific lower limb vascular examination should include palpation of femoral, popliteal, dorsalis pedis and posterior tibial artery pulses. These pulses should be assessed bilaterally and pulse abnormalities correlated with limb symptoms, oscillometric measurements and findings from arterial imaging.

Patients with a history or clinical examination suggestive of PAD should undergo objective diagnostic testing such as determination of ABI, oscillometric measurement and duplex ultrasound. Doppler ultrasound measurement of ankle artery pressures and their relation to brachial pressure (assessment of the ankle-brachial index [ABI]) remains the most effective, accurate and practical non-invasive test for both the detection of PAD and for the assessment of haemodynamic efficacy after revascularisation [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines., 1515. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, Jones DN. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg. 1997;26:517-38. , 1616. Diehm N, Baumgartner I, Jaff M, Do DD, Minar E, Schmidli J, Diehm C, Biamino G, Vermassen F, Scheinert D, van Sambeek MR, Schillinger M. A call for uniform reporting standards in studies assessing endovascular treatment for chronic ischaemia of lower limb arteries. Eur Heart J. 2007;28:798-805. , 1717. Diehm N, Pattynama PM, Jaff MR, Cremonesi A, Becker GJ, Hopkins LN, Mahler F, Talen A, Cardella JF, Ramee S, van Sambeek M, Vermassen F, Biamino G. Clinical endpoints in peripheral endovascular revascularization trials: a case for standardized definitions. Eur J Vasc Endovasc Surg. 2008;36:409-19.
Consensus manuscript for endpoint definitions in endovascular PAD trials.]. A resting ABI <0.9 approaches a 95% sensitivity for the presence of PAD and 99% specificity in excluding individuals without impairment of arterial perfusion [1818. Criqui MH, Fronek A, Klauber MR, Barrett-Connor E, Gabriel S. The sensitivity, specificity, and predictive value of traditional clinical evaluation of peripheral arterial disease: results from noninvasive testing in a defined population. Circulation. 1985;71:516-22. ] ( Figure 1). In claudicants with normal lower limb pulses and ABI at rest, exercise testing should be performed. Patients with IC and relevant arterial obstruction will typically exhibit a > 20 mmHg drop in post-exercise ankle pressures. Of note is isolated severe disease of the internal iliac artery which can result in buttock claudication and impotence in males and is not captured by peripheral pulses palpation measurement of ABI.

The presence of medial arterial calcification is frequently found in patients with diabetes mellitus, renal insufficiency, long lasting steroid treatment and older age. This can result in falsely elevated ABI which independently predicts adverse outcomes [1919. Silvestro A, Diehm N, Savolainen H, Do DD, Vogelea J, Mahler F, Zwicky S, Baumgartner I. Falsely high ankle-brachial index predicts major amputation in critical limb ischemia. Vasc Med. 2006;11:69-74. , 2020. Willenberg T, Diehm N, Zwahlen M, Kalka C, Do DD, Gretener S, Ortmann J, Baumgartner I. Impact of long-term corticosteroid therapy on the distribution pattern of lower limb atherosclerosis. Eur J Vasc Endovasc Surg. 39:441-6 ]. In the case of a falsely elevated ABI, toe pressure measurements, photoplethysmographic and oscillometric, are mandatory for the quantification of lower limb perfusion.

Colour-coded duplex sonography is warranted for non-invasive assessment of the amenability for surgical or endovascular revascularisation. Thereby the lower extremity arterial tree can be visualised, and the extent and degree of atherothrombotic lesions accurately assessed and arterial flow velocities measured. Moreover, duplex ultrasound can be used to assess calcifications of puncture sites potentially precluding vascular access. Finally, the use of duplex ultrasound can help to minimise the need for contrast material in PAD patients with functional renal impairment scheduled for endovascular intervention. It should be noted that the clinical utility of duplex ultrasound in assessing infra-popliteal obstructions is limited [2121. Bosiers M, Peeters P, D’Archambeau O, Hendriks J, Pilger E, Duber C, Zeller T, Gussmann A, Lohle PN, Minar E, Scheinert D, Hausegger K, Schulte KL, Verbist J, Deloose K, Lammer J. AMS INSIGHT -absorbable metal stent implantation for treatment of below-the-knee critical limb ischemia: 6-month analysis. Cardiovasc Intervent Radiol. 2009;32:424-35. ].

Since the prevalence of abdominal aortic aneurysms in patients with PAD is significantly higher than that reported for the general population [2222. Barba A, Estallo L, Rodriguez L, Baquer M, Vega de Ceniga M. Detection of abdominal aortic aneurysm in patients with peripheral artery disease. Eur J Vasc Endovasc Surg. 2005;30:504-8. ], it is suggested that an abdominal ultrasound quick-screen be routinely included in the study of patients with PAD [2323. Fleming C, Whitlock EP, Beil TL, Lederle FA. Screening for abdominal aortic aneurysm: a best-evidence systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2005;142:203-11. ].

Magnetic resonance angiography (MRA) has evolved as an imaging technique for the diagnosis and treatment planning of patients with PAD [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines., 2424. Fleischmann D, Lammer J. Peripheral CT angiography for interventional treatment planning. Eur Radiol. 2006;16 Suppl 7:M58-64. , 2525. Diehm N, Kickuth R, Baumgartner I, Srivastav SK, Gretener S, Husmann MJ, Jaccard Y, Do do D, Triller J, Bonel HM. Magnetic resonance angiography in infrapopliteal arterial disease: prospective comparison of 1.5 and 3 Tesla magnetic resonance imaging. Invest Radiol. 2007;42:467-76. ]. The advantages of MRA include its safety and ability to provide high-resolution three-dimensional imaging of the entire abdominal and lower limb vasculature in one setting. Moreover, pre-interventional MRI can help to minimise both the use of iodinated contrast material and exposure to radiation. A recent concern in the use of gadolinium-enhanced MRI is nephrogenic systemic fibrosis, with an incidence of 1% to 6% for dialysis patients, and GFR <30 mL/min is designated as a relative contraindication.

Multi-detector computed tomography angiography is being used widely for the diagnostic evaluation and treatment planning of PAD [2424. Fleischmann D, Lammer J. Peripheral CT angiography for interventional treatment planning. Eur Radiol. 2006;16 Suppl 7:M58-64. ]. It is of particular value for the imaging of the aorto-iliac segment in patients in whom the diagnostic yield of duplex ultrasound is limited due to obesity or severe arterial calcification. Moreover, it enables rapid imaging of the entire lower extremity and abdomen in one breath-hold at very high spatial resolution. The major limitations of computed tomography angiography, however, include the need for iodinated contrast and radiation exposure.

Intra-arterial digital subtraction angiography using iodinated contrast is still considered the gold standard for evaluation of the lower limb obstructive lesion morphology in PAD patients despite a certain morbidity risk associated with the invasiveness of the procedure. Today however, considering the above-mentioned non-invasive and reliable diagnostic tools, it is very rarely performed as the primary pre-revascularisation workup diagnostic in PAD patients.

In summary, the risks and benefits of either diagnostic method must be carefully weighed up and tailored to the individual patient needs. The non-invasive imaging method used, mainly depends on the clinical scenario and individual availability at the treating centres.

Clinical classification of chronic peripheral arterial occlusive disease

In patients with chronic PAD the first symptom is usually IC which manifests itself in limited walking ability with discomfort of the lower limbs (muscle fatigue or cramping), produced by exercise and relieved by rest. These symptoms are usually localised distally to the level of arterial obstruction. Symptoms may involve the buttocks if the arterial obstruction is localised in the abdominal aorta and/or common and internal iliac arteries, the thigh if there is an obstruction of external iliac and/or common femoral arteries and the calf if obstructions involve the femoro-popliteal or tibial arteries. The severity of intermittent claudication ( Table 1) can be quantified in terms of patient walking distance using a graded treadmill test. In sedentary patients and in diabetics with peripheral neuropathies, PAD at this stage can be asymptomatic and claudication may not necessarily occur.

The term CLI describes patients with a history of chronic ischaemic rest pain and/or tissue loss for more than two weeks. Importantly, the clinical diagnosis of CLI must be confirmed by objective haemodynamic criteria: CLI occurs below an ankle pressure <50-70 mmHg, a toe pressure <30 mmHg and a transcutaneous oxygen partial pressure <20-30 mmHg [2626. Michaels J. Second European Consensus Document on Chronic Critical Limb Ichaemia. Eur J Vasc Surg. 1993; 7:223. ].

The diabetic foot

The presence of diabetes increases the frequency IC by 3-fold in males and by 8-fold in females [2727. Diabetes-related amputations of lower extremities in the Medicare population – Minnesota, 1993-1995. MMWR Morb Mortal Wkly Rep. 1998;47:649-52. ]. Moreover, it increases the risk of lower limb amputation by 20-fold in patients aged from 65 to 74 [2727. Diabetes-related amputations of lower extremities in the Medicare population – Minnesota, 1993-1995. MMWR Morb Mortal Wkly Rep. 1998;47:649-52. ].

The most distinguishing feature of atherosclerosis in patients with diabetes mellitus is the more rapid disease progression, the high incidence of medial arterial calcification and the pattern in which it occurs in the lower limb arteries. Arterial obstructions tend to involve the infra-genicular arteries, whereas the foot arteries are relatively spared [99. Diehm N, Shang A, Silvestro A, Do DD, Dick F, Schmidli J, Mahler F, Baumgartner I. Association of Cardiovascular Risk Factors with Pattern of Lower Limb Atherosclerosis in 2659 Patients Undergoing Angioplasty. Eur J Vasc Endovasc Surg. 2006;31:59-63. , 2828. Diehm N, Rohrer S, Baumgartner I, Keo H, Do D, Kalka C. Distribution pattern of infrageniculate arterial obstructions in patients with diabetes mellitus and renal insufficiency – implications for revascularization. Vasa. 2008;37:265-73. ].

Peripheral neuropathy is a common complication of diabetes. It leads to sensory loss, atrophy of intrinsic muscles with development of foot deformities and build-up of pressure points which makes the foot more susceptible to ulceration even at lesser degrees of ischaemia. Thus, diabetic foot ulcerations can be divided into three broad categories: ischaemic, neuro-ischaemic and neuropathic. It should be noted that PAD can be asymptomatic in diabetic patients with peripheral neuropathy therefore the first clinical symptom of PAD can be skin ulceration.

In diabetic PAD patients with media calcinosis or severe infra-popliteal arterial calcification the incompressibility of distal arteries can cause falsely elevated ABI measurements. In these cases measurement of toe pressure or transcutaneous oxygen partial pressure should be implemented. Interestingly, a falsely elevated ABI was shown to confer a similar risk of amputation as a low ABI [1919. Silvestro A, Diehm N, Savolainen H, Do DD, Vogelea J, Mahler F, Zwicky S, Baumgartner I. Falsely high ankle-brachial index predicts major amputation in critical limb ischemia. Vasc Med. 2006;11:69-74. ].

PAD is very common in patients affected by chronic renal insufficiency. The prevalence of PAD in patients > 40 years with creatinine clearance < 60 mL/min (1.73 m2) was shown to be 24% as compared to 3.7% of the population with normal renal function [2929. Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, Golden SH. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med. 2004;141:421-31. ]. Histologically, atherosclerotic occlusive disease is characterised by heavy calcification while the occlusive process, in contrast to that seen in diabetics, tends to involve both tibial and foot arteries [2828. Diehm N, Rohrer S, Baumgartner I, Keo H, Do D, Kalka C. Distribution pattern of infrageniculate arterial obstructions in patients with diabetes mellitus and renal insufficiency – implications for revascularization. Vasa. 2008;37:265-73. ].

Therapeutic strategy for chronic peripheral obstructive disease

Whilst all PAD patients should be treated with the below-mentioned secondary preventive measures, the decision to apply invasive revascularisation strategies will depend on the extent of patients` symptoms and comorbidities as well as localisation and the extent of arterial obstructions.

In claudicants, the key treatment aims are improvement in the patient’s walking ability and quality of life as well as the prevention of PAD disease progression. In contrast, the major goal in CLI patients is to relieve ischaemic pain, heal skin lesions and prevent major amputation. Whilst arterial revascularisation is optional for most claudicants, it should be attempted whenever possible in patients with CLI. In addition, a comprehensive evaluation of global cardiovascular risk should be performed for all PAD patients in order to identify those at higher risk of life-threatening cardiovascular events.

CONSERVATIVE THERAPIES

Risk factor modification

Since PAD patients who keep smoking exhibit a significantly increased probability of progression of atherosclerosis, including limb loss, myocardial infarction, stroke and death [3030. Smith I, Franks PJ, Greenhalgh RM, Poulter NR, Powell JT. The influence of smoking cessation and hypertriglyceridaemia on the progression of peripheral arterial disease and the onset of critical ischaemia. Eur J Vasc Endovasc Surg. 1996;11:402-8. , 3131. Birkenstock WE, Louw JH, Terblanche J, Immelman EJ, Dent DM, Baker PM. Smoking and other factors affecting the conservative management of peripheral vascular disease. S Afr Med J. 1975;49:1129-32. ], smoking cessation is the key accomplishment to be attained. An appropriate control of diabetes mellitus foresees haemoglobin A1c values below 7% [3232. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-53. ]. Lipid-lowering therapy in PAD patients with LDL cholesterol values >125 mg/dl is recommended with LDL target values of <100 mg/dl [3333. American Diabetes Association. Peripheral Arterial Disease in People With Diabetes. Diabetes Care. 2003;26:3333-41. ]. A rigid control of arterial hypertension to values <140/90 mmHg (and 130/80 mmHg in patients with additional diabetes mellitus or renal insufficiency) is aimed at reducing the subsequent risk for stroke, myocardial infarction and cardiovascular death. Table 2 summarises conservative treatment approaches for PAD patients.

Pharmacotherapy

Different studies on antiplatelet therapy indicate their effectiveness in reducing myocardial infarction, stroke and death from cardiovascular disease [3434. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Brit Med J. 2002;324:71-86. , 3535. Sobel M, Verhaeghe R. Antithrombotic Therapy for Peripheral Artery Occlusive Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:815S-43. , 3636. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706-17. ]. Whilst the effectiveness of antiplatelet agents in reducing the incidence of atherothrombotic complications is well studied, there is no evidence as to a beneficial contribution regarding functional improvements in PAD symptoms. Moreover, it has been shown in a randomised study that antiplatelet therapy yields higher arterial patency rates subsequent to endovascular arterial revascularisation [3737. Heiss HW, Just H, Middleton D, Deichsel G. Reocclusion prophylaxis with dipyridamole combined with acetylsalicylic acid following PTA. Angiology. 1990;41:263-9. ]. Consequently, all PAD patients should be treated with antiplatelet agents (except those with specific contraindications, Table 2 ).

Recent evidence suggests consistent benefit in adding a low-dose anticoagulant agent in patients with PAD. The Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial has been developed to study for the first time the role of a DOAC, rivaroxaban, in patients with stable CAD or PAD at high risk for ischemic events [3838. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319–1330. ]. In this double-blind trial, 27,395 participants with stable atherosclerotic vascular disease were randomized to receive rivaroxaban (2.5 mg twice daily) plus ASA, rivaroxaban (5 mg twice daily), or ASA alone. The study was stopped for superiority of the rivaroxaban (2.5 mg twice daily) plus ASA group after a mean follow-up of 23 months. The rate of the primary outcome, a composite of CV death, stroke, or MI, was lower with rivaroxaban plus ASA than with ASA alone (HR 0.76; 95% CI 0.66–0.86; P < 0.001), as were total mortality, coronary heart disease mortality, and CV mortality. Major bleedings, according to modified International Society on Thrombosis and Hemostasis (ISTH) criteria, were increased in the combination arm (HR 1.70; 95% CI, 1.40–2.05; P < 0.001), but not intracranial or fatal bleeding.
More recently, the efficacy of rivaroxaban in patients with PAD undergoing lower extremity revascularization has been investigated in the Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities (VOYAGER-PAD) [3939. Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med. 2020;382:1994–2004. ]. More than 6,500 patients over 50 years of age with symptomatic

lower extremity PAD who underwent successful infra-inguinal revascularization within the preceding 7 days were randomized to receive rivaroxaban (2.5 mg twice daily) and ASA or ASA alone in addition to standard background therapy. At 3 years, rivaroxaban significantly reduced the rate of the primary endpoint (a composite of acute limb ischemia, major amputation for vascular causes, MI, ischemic stroke, or death from CV causes) compared to placebo (HR 0.85, 95% CI, 0.76 to 0.96; P = 0.009), without increasing the rate of major bleeding according to the TIMI classification.

Vasoactive drugs such as Cilostazol or Naftidrofuryl may be used in patients with lifestyle-limiting claudication in whom exercise training or arterial revascularisation cannot be accomplished [4040. Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med. 2001;344: 1608-21. , 4141. De Backer TL, Vander Stichele R, Lehert P, Van Bortel L. Naftidrofuryl for intermittent claudication. Cochrane Database Syst Rev. 2008; CD001368. ].

Intravenous therapy with prostanoids is indicated only in CLI patients unsuitable for revascularisation or in those patients with revascularisation failures whose only alternative is major amputation.

Pain control in PAD is necessary to improve quality of life. Narcotics can be used for a short period. Epidural single shot or continuous epidural analgesia are a valid choice for pain control before and subsequent to arterial revascularisation. An adequate ischaemic pain control is essential for CLI patients. Analgesia, however, must not postpone revascularisation of arterial obstructions.

Exercise rehabilitation

Exercise training has a pivotal role for claudicants. However, this therapy only offers best results when performed under medical supervision and three times per week [4242. Clifford PC, Davies PW, Hayne JA, Baird RN. Intermittent claudication: is a supervised exercise class worth while?. Br Med J. 1980;280:1503-5. , 4343. Patterson RB, Pinto B, Marcus B, Colucci A, Braun T, Roberts M. Value of a supervised exercise program for the therapy of arterial claudication. J Vasc Surg. 1997;25:312-8; discussion 8-9. , 4444. Regensteiner JG, Meyer TJ, Krupski WC, Cranford LS, Hiatt WR. Hospital vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease. Angiology. 1997;48:291-300. ]. A recent meta-analysis of various studies has highlighted an average 122% increase in maximum walking capacity [4545. Spronk S, Bosch JL, den Hoed PT, Veen HF, Pattynama PM, Hunink MM. Cost-effectiveness of endovascular revascularization compared to supervised hospital-based exercise training in patients with intermittent claudication: A randomized controlled trial. J Vasc Surg. 2008;48:1472-80. ]. However, exercise training cannot be performed for a variety of reasons in about one third of claudicants. Moreover, a further third of patients are not willing to undergo rehabilitation. A history of claudication of shorter than one year, good cardiopulmonary condition and occlusions of the superficial femoral artery are predictors of a favourable response to exercise training. In contrast, patients with obstructions of the iliac arteries do not respond well to exercise training. It must be kept in mind that exercise training is cumbersome in CLI patients.

Local treatment of ischaemic skin lesions

Clinical success in PAD patients with stage IV disease does not rely solely on arterial revascularisation. Wound management is of equal importance and aims at neutralising other aetiological factors and at prevention of local complications. To tailor wound care strategies to specific patients, it seems crucial to frame the observed wound in a clinical context that considers the characteristics of the wound, the limb and the whole patient. Among other proposed classifications, the most widely used is currently the WIfI system [4646. Mills JL Sr, Conte MS, Armstrong DG, et al. Society for VAscular Surgery Lower Extremity Guidelines C. The Society for VAscular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg. 2014; 59:220-234. ]. This scoring system evaluates Wound depth, Ischemia degree and foot Infection degree, thus being able to provide an immediate glimpse of the overall risk for the affected limb.

An interdisciplinary wound care team should take care of off-loading of the wound region and any region at risk from inadequate increase in pressure or sheer stress induced by inadequate shoes. Local surgical management includes debridement of necrotic or fibrous tissues and timely removal of necrotic toes that can serve as a source for infections. In general, a dry wound environment should be maintained and additional wound trauma should be prevented by the use of non-adherent gauzes. Vacuum-assisted devices are valuable additional tools aimed at improving local wound care. However, care must be taken to adapt the amount of negative pressure to the impaired perfusion to avoid iatrogenic perpetuation of ischaemia. Systemic antibiotic therapy is required in CLI patients with cellulitis or spreading infection [33. Criqui MH, Fronek A, Barret-Connor EK, Klauber MR, Gabriel S, Goodman D. The prevalence of peripheral arterial disease in a defined population. Circulation. 1985;71:510-5. , 2626. Michaels J. Second European Consensus Document on Chronic Critical Limb Ichaemia. Eur J Vasc Surg. 1993; 7:223. ].

Alternative treatments

Spinal cord stimulation can be used in CLI patients not suitable for revascularisation [4747. Ubbink DT, Vermeulen H. Spinal cord stimulation for non-reconstructable chronic critical leg ischaemia. Cochrane Database Syst Rev. 2003;CD004001. ].

There is no scientifically sound evidence to support the use of other treatments such as oxygen-multiple-step therapy, oxidation or ozone therapy or fresh cell therapy.

ARTERIAL REVASCULARISATION

In the management of patients with lifestyle-limiting or disabling claudication, revascularisation should be considered if regular exercise and other non-interventional therapies cannot be accomplished or have failed. In CLI patients however, revascularisation should be considered as the first-line treatment option in conjunction with therapy for local symptoms (pain and infection control) as well as secondary preventive measures.

Lower limb revascularisation can be accomplished using endovascular or open surgical techniques. The choice between endovascular and surgical revascularisation largely depends on the anatomical level (aorto-iliac, femoro-popliteal and infrapopliteal disease) and the extent (stenosis versus occlusion and the length of the lesion) of the arterial obstruction. If both techniques are equally feasible with similar technical success rates and mid-term clinical outcomes, the less invasive technique should be preferred. Endovascular and open surgical revascularisation should be regarded as complementary, but not as competing treatment methods and the choice of the specific procedure should be individually tailored to the specific patient’s needs.

Endovascular techniques include balloon angioplasty, drug-coated balloons, balloon-expandable and self-expanding stents, drug-eluting stents, stent-grafts and plaque debulking procedures, whereas surgical options include bypass (with autologous, synthetic or cryopreserved grafts), endarterectomy or hybrid procedures (including surgical and endovascular components).

Aorto-iliac revascularisation

Iliac artery obstructions have traditionally been treated by open surgery e.g., aorto-femoral or aorto-bifemoral bypass grafting. This treatment is highly effective: patency rates of 91% (90% to 94%) at 5 years and 86.8% (85% to 92%) at 10 years have been reported for claudicants. In contrast, patency was reported to be 87.5% (80% to 88%) at 5 years and 81.8% (70% to 85%) at 10 years in CLI patients, with a perioperative mortality rate of 3.3% and morbidity of 8.3% [4848. de Vries SO, Hunink MG. Results of aortic bifurcation grafts for aortoiliac occlusive disease: a meta-analysis. J Vasc Surg. 1997;26:558-69. ]. This treatment is generally performed through a trans-peritoneal approach. Alternative approaches, such as the retroperitoneal or laparoscopic approach, have been suggested [4949. Lord RS, Crozier JA, Snell J, Meek AC. Transverse abdominal incisions compared with midline incisions for elective infrarenal aortic reconstruction: predisposition to incisional hernia in patients with increased intraoperative blood loss. J Vasc Surg. 1994;20:27-33. , 5050. Dion YM, Gracia CR. A new technique for laparoscopic aortobifemoral grafting in occlusive aortoiliac disease. J Vasc Surg. 1997;26:685-92. , 5151. Sicard GA, Reilly JM, Rubin BG, Thompson RW, Allen BT, Flye MW, Schechtman KB, Young-Beyer P, Weiss C, Anderson CB. Transabdominal versus retroperitoneal incision for abdominal aortic surgery: report of a prospective randomized trial. J Vasc Surg. 1995;21:174-81; discussion 81-3. ]. Interest in aortic endarterectomy has gradually declined due to excellent results with bypass. Currently aortic endarterectomy is mostly reserved for young patients, patients with short lesions unsuitable for endovascular treatment and patients at high risk for infection. Patency rates at 5 years in the latter method vary between 60% and 94% [5252. Roder OC, Eickhoff J, Jorgensen SJ. Thromboendarterectomy vs. aortic bifurcation graft for unilateral iliac artery atherosclerosis. Acta Chir Scand. 1985;151:345-8. , 5353. Vitale GF, Inahara T. Extraperitoneal endarterectomy for iliofemoral occlusive disease. J Vasc Surg. 1990;12:409-13; discussion 14-5. , 5454. Oskam J, van den Dungen JJ, Boontje AH. Thromboendarterectomy for obstructive disease of the common iliac artery. Cardiovasc Surg. 1996;4:356-9. ]. Extra-anatomical bypass can be performed in patients at high surgical risk or with hostile abdomen. The subclavian artery, the descending thoracic aorta or the contralateral iliac and femoral arteries can be used as donor vessels. Five-year patency rates range from 30% to 79% for axillo-femoral bypasses, from 33% to 85% for axillo-bifemoral bypasses, from 55% to 92% in femoro-femoral crossover bypasses while they are 80% for thoraco-femoral bypasses [5555. Ascer E, Veith FJ, Gupta SK, Scher LA, Samson RH, White-Flores SA, Sprayregen S. Comparison of axillounifemoral and axillobifemoral bypass operations. Surgery. 1985;97:169-75. , 5656. Rutherford RB, Patt A, Pearce WH. Extra-anatomic bypass: a closer view. J Vasc Surg. 1987;6:437-46. , 5757. el-Massry S, Saad E, Sauvage LR, Zammit M, Davis CC, Smith JC, Rittenhouse EA, Fisher LD. Axillofemoral bypass with externally supported, knitted Dacron grafts: a follow-up through twelve years. J Vasc Surg. 1993;17:107-14; discussion 14-5. , 5858. Passman MA, Farber MA, Criado E, Marston WA, Burnham SJ, Keagy BA. Descending thoracic aorta to iliofemoral artery bypass grafting: a role for primary revascularization for aortoiliac occlusive disease?. J Vasc Surg. 1999;29:249-58. , 5959. Hepp W, de Jonge K, Pallua N. Late results following extra-anatomic bypass procedures for chronic aortoiliac occlusive disease. J Cardiovasc Surg. (Torino) 1988;29:181-5. , 6060. Chang JB. Current state of extraanatomic bypasses. Am J Surg. 1986;152:202-5. , 6161. Harrington ME, Harrington EB, Haimov M, Schanzer H, Jacobson JH, 2nd. Axillofemoral bypass: compromised bypass for compromised patients. J Vasc Surg. 1994;20:195-201. , 6262. McCarthy WJ, Mesh CL, McMillan WD, Flinn WR, Pearce WH, Yao JS. Descending thoracic aorta-to-femoral artery bypass: ten years’ experience with a durable procedure. J Vasc Surg. 1993;17:336-47; discussion 47-8. , 6363. Kalman PG, Johnston KW, Walker PM. Descending thoracic aortofemoral bypass as an alternative for aortoiliac revascularization. J Cardiovasc Surg. (Torino) 1991;32:443-6. , 6464. Passman MA, Taylor LM, Moneta GL, Edwards JM, Yeager RA, McConnell DB, Porter JM. Comparison of axillofemoral and aortofemoral bypass for aortoiliac occlusive disease. J Vasc Sur. g 1996;23:263-9; discussion 9-71. , 6565. Lorenzi G, Domanin M, Costantini A, Rolli A, Agrifoglio G. Role of bypass, endarterectomy, extra-anatomic bypass and endovascular surgery in unilateral iliac occlusive disease: a review of 1257 cases. Cardiovasc Surg. 1994;2:370-3. , 6666. Perler BA, Williams GM. Does donor iliac artery percutaneous transluminal angioplasty or stent placement influence the results of femorofemoral bypass?. Analysis of 70 consecutive cases with long-term follow-up. J Vasc Surg. 1996;24:363-9; discussion 9-70. , 6767. Ng RL, Gillies TE, Davies AH, Baird RN, Horrocks M. Iliofemoral versus femorofemoral bypass: a 6-year audit. Br J Surg. 1992;79:1011-3. ].

Percutaneous transluminal angioplasty (PTA) is a less invasive alternative and has proven to be an effective technique for the treatment of iliac artery lesions in the last years ( Figure 2 and Figure 3A, Figure 3B, Figure 3C) [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines.]. In our experience, most iliac artery lesions can be treated utilising an ipsilateral retrograde access, whereas antegrade recanalisation using a cross-over or left brachial approach may be necessary in chronic occlusions. The reported success rate is 85% to 99% (mean 95%). Adjunctive stent implantation has even increased primary success rates to 95% to 100% (mean 99%) [6868. Mouanoutoua M, Maddikunta R, Allaqaband S, Gupta A, Shalev Y, Tumuluri R, Bajwa T. Endovascular intervention of aortoiliac occlusive disease in high-risk patients using the kissing stents technique: long-term results. Catheter Cardiovasc Interv. 2003;60:320-6. ]. The current indications for iliac arteries stenting are elastic recoil, dissection and thrombosis after PTA, chronic occlusion, restenosis and complex lesions. Balloon-expandable stents should be chosen for implantation in short lesions of the common iliac artery while self-expanding stents may be considered for long, less calcified, non-ostial lesions in the external iliac artery. The five-year patency rate after endovascular therapy for iliac artery stenoses is 80% to 90%, whereas long-term patency for PTA of complete iliac occlusions is reported to be 20% lower than that for iliac stenoses [6868. Mouanoutoua M, Maddikunta R, Allaqaband S, Gupta A, Shalev Y, Tumuluri R, Bajwa T. Endovascular intervention of aortoiliac occlusive disease in high-risk patients using the kissing stents technique: long-term results. Catheter Cardiovasc Interv. 2003;60:320-6. , 6969. Tetteroo E, Haaring C, van der Graaf Y, van Schaik JP, van Engelen AD, Mali WP. Intraarterial pressure gradients after randomized angioplasty or stenting of iliac artery lesions. Dutch Iliac Stent Trial Study Group. Cardiovasc Intervent Radiol. 1996;19:411-7. ].

Femoro-popliteal revascularisation

The low morbidity and mortality of endovascular techniques such as percutaneous transluminal angioplasty (PTA) and stent implantation makes it the preferred choice for most arterial obstructions in the femoro-popliteal segment. A key issue for successful endovascular intervention is selection of the appropriate vascular access. Two standard approaches are available for femoral, popliteal and tibial artery interventions, the cross-over and the antegrade approach.

The cross-over approach from the common femoral artery is the standard access technique for femoro-popliteal interventions in various centres. In contrast, other interventionalists prefer the antegrade approach as it provides more direct access to many lesions in the medial and distal femoro-popliteal segment and to the infra-geniculate arteries in which substantial friction, due to presence of severe calcifications, can be encountered.

Antegrade puncture can be technically more challenging in obese patients. Other possibilities include the transpopliteal and pedal approaches. Special care must be taken during arterial access attempts in order to avoid dissection of potential receiving segments for bypass surgery in case endovascular therapy fails.

The technical success rate of PTA in femoro-popliteal artery stenoses and occlusions exceeds 95% and 85%, respectively. Introduction of dedicated devices to re-enter the artery subsequent to subintimal recanalisation has substantially improved technical success rates even in long and very calcified femoro-popliteal occlusions. There is general agreement that for acute failure of PTA (e.g., due to thrombosis, flow-limiting dissections or residual stenosis), stent placement is indicated. Current studies show that restenosis subsequent to plain balloon angioplasty occurs in every third patient [7070. Krankenberg H, Schluter M, Steinkamp HJ, Burgelin K, Scheinert D, Schulte KL, Minar E, Peeters P, Bosiers M, Tepe G, Reimers B, Mahler F, Tubler T, Zeller T. Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST). Circulation. 2007;116:285-92. , 7171. Laird JR, Katzen BT, Scheinert D, Lammer J, Carpenter J, Buchbinder M, Dave R, Ansel G, Lansky A, Cristea E, Collins TJ, Goldstein J, Jaff MR. Nitinol stent implantation versus balloon angioplasty for lesions in the superficial femoral artery and proximal popliteal artery: twelve-month results from the RESILIENT randomized trial. Circ Cardiovasc Interv. 3:267-76. , 7272. Schillinger M, Sabeti S, Loewe C, Dick P, Amighi J, Mlekusch W, Schlager O, Cejna M, Lammer J, Minar E. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med. 2006;354:1879-88. ].

In the femoro-popliteal arteries, highly flexible nitinol stents are preferred over balloon-expandable stents. Short balloon-expandable stents might be beneficial in lesions at the ostium of the superficial femoral artery where precise placement is mandatory to preserve flow into the deep femoral artery and, in rare situations, for spot stenting of very short lesions. In the case of stent deployment within the bending segment of the femoro-popliteal artery, flexion angiography prior to stent placement may be helpful to understand better the biomechanical prerequisites of the treated segment and modify stent placement accordingly ( Figure 4A, Figure 4B). The diameter of self-expanding nitinol stents should be ≈10% larger than the reference vessel.

Post-dilatation for adaptation of the stent is recommended, especially in highly calcified lesions.

Whilst primary stenting currently has no established role in short femoro-popliteal lesions [7070. Krankenberg H, Schluter M, Steinkamp HJ, Burgelin K, Scheinert D, Schulte KL, Minar E, Peeters P, Bosiers M, Tepe G, Reimers B, Mahler F, Tubler T, Zeller T. Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST). Circulation. 2007;116:285-92. ], primary stent placement is superior to balloon angioplasty plus optional stenting in long and complex femoro-popliteal lesions [7272. Schillinger M, Sabeti S, Loewe C, Dick P, Amighi J, Mlekusch W, Schlager O, Cejna M, Lammer J, Minar E. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med. 2006;354:1879-88. ]. In summary, the need for stents in the femoro-popliteal arterial segment increases with lesion length and complexity as well as the clinical presentation shifts towards severe ischaemia.

In spite of a net increase of immediate clinical success, stent placement in the femoropopliteal region has got some limitations. Superficial femoral artery has got unique and peculiar anatomical characteristics as it must withstand, at the same time, different and contrasting forces of torsion, compression, stretching, flexion and extension. For these reasons, the idea of ‘leaving nothing behind’ and still using an anti-proliferative drug has gained a widespread diffusion during the last years. Three different drug-coated balloons showed a patency of 90% in the first year, with need for re-operation ranging from 2.4% to 12.3% [7373. Laird JR, Schneider PA, Tepe G, Brodmann M, Zeller T, Metzger C, Krishnan P, Scheinert D, Micari A, Cohen DJ, Wang H, Hasenbank MS, Jaff MR; IN. PACT SFA Trial Investigators. Durability of treatment effect using a drug-coated balloon for femoropopliteal lesions: 24-month results of IN. PACT SFA. J Am Coll Cardiol. 2015;66:2329-2338. , 7474. Krishnan P, Faries P, Niazi K, Jain A, Sachar R, Bachinsky WB, Cardenas J, Werner M, Brodmann M, Mustapha JA, Mena-Hurtado C, Jaff MR, Holden AH, Lyden SP. Stellarex Drug-Coated Balloon for Treatment of Femoropopliteal Disease: Twelve-Month Outcomes From the Randomized ILLUMENATE Pivotal and Pharmacokinetic Studies. Circulation. 2017;136:1102-1113. , 7575. Rosenfield K, Jaff MR, White CJ, Rocha-Singh K, Mena-Hurtado C, Metzger DC, Brodmann M, Pilger E, Zeller T, Krishnan P, Gamon R, Müller-Hülsbeck S, Nehler MR ]. Although the potential cytotoxicity of paclitaxel in relation to systemic chemotherapy regimens has been well-delineated, additional concerns about its role in the treatment of peripheral arterial disease stem from a potential correlation to increased all-cause mortality, as suggested in a 2018 study by Katsanos et al.[7676. Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2018;7:e011245. ]. Conversely, the results of a 2019 meta-analysis by Schneider et al. did not show a significant difference in the 5-year mortality rates between those patients treated with percutaneous transluminal angioplasty (PTA) and paclitaxel DCB [7777. Schneider PA, Laird JR, Doros G, Gao Q, Ansel G, Brodmann M, Micari A, Shishehbor MH, Tepe G, Zeller T. Mortality not correlated with paclitaxel exposure: an independent patient-level meta-analysis of a drug-coated balloon. J Am Coll Cardiol. 2019;73:2550–63. ] In addition, of those patients treated with paclitaxel DCB, there was no dose-related increased mortality risk, and of those risk factors found to be predictors of increased mortality (which was largely related to the underlying disease process itself), exposure to paclitaxel was not found to be one of them.

Similarly, Secemsky et al. performed a multicentre retrospective cohort study using Medicare and Medicaid real-world data comparing drug-coated devices with standard non-drug-coated devices in the treatment of femoropopliteal PAD. Multivariate analysis suggested there was no difference in all-cause mortality between the two groups, which was consistent across patients with and without critical limb ischaemia and irrespective of the type of drug-coated device used (DCB or drug-eluting stent) [7878. Secemsky EA, Kundi H, Weinberg I, Jaff MR, Krawisz A, Parikh SA, Beckman JA, Mustapha J, Rosenfield K, Yeh RW. Association of Survival With Femoropopliteal Artery Revascularization With Drug-Coated Devices. JAMA Cardiol. 2019;4:332-340. ].

It is easy to understand how the use of drug-coated devices in the treatment of femoropopliteal disease has become a topic of controversy, with many physicians strongly reducing the use of drug-coated devices in peripheral interventions. However, it should be acknowledged that, lacking full and comprehensive studies focused on the long-term risks and benefits of paclitaxel using real patient data, without a consistent dose response, underlying pharmacokinetic mechanism and reproducible harm, it is difficult to infer that paclitaxel-coated devices are the cause of increased all-cause mortality. This appears to be only an association between paclitaxel-coated devices and increased all-cause mortality, not a causation.

On the other side, a recognized limitation of the drug eluting balloons is their lack of scaffolding. In peripheral artery disease the arteries are often severely calcified, with the calcium constituting on one hand a barrier for the drug elution, and on the other a strong predictor of vessel elastic recoil in the short term. Accordingly, a careful assessment of lesion calcification and length should always guide the operators in drug-eluting device selection and tailor interventional treatment according to clinical indications (CLI vs. IC). For these reasons, especially when stent implantation is to be avoided, lesion preparation is crucial. Currenty available devices for lesion preparation include cutting balloons and atherectomy devices. Currently available atherectomy devices and their main technical characteristics are summarized in Table 3.

Finally, bypass surgery (preferably utilising autologous vein) is the treatment of choice in patients with long and highly calcified lesions involving the full length of the popliteal artery, primarily in CLI patients. Above-knee bypass in patients with CLI performed with autologous veins has a 5-year primary patency rate of 80%, this percentage is 75% in PTFE bypass [7979. Hunink MG, Wong JB, Donaldson MC, Meyerovitz MF, Harrington DP. Patency results of percutaneous and surgical revascularization for femoropopliteal arterial disease. Med Decis Making. 1994;14:71-81. ]. In contrast, primary patency after 5 years is 66% with autologous vein and 47% with PTFE in CLI patients [7979. Hunink MG, Wong JB, Donaldson MC, Meyerovitz MF, Harrington DP. Patency results of percutaneous and surgical revascularization for femoropopliteal arterial disease. Med Decis Making. 1994;14:71-81. ]. Isolated thrombendarterectomy of the profunda femoris artery is recommended in claudicants with good flow to the infrapopliteal arteries. The isolated use of these technique in patients with CLI appears to be controversial [8080. Diehm N, Savolainen H, Mahler F, Schmidli J, Do DD, Baumgartner I. Does deep femoral artery revascularization as an isolated procedure play a role in chronic critical limb ischemia?. J Endovasc Ther. 2004;11:119-24. ].

Infra-popliteal revascularisation

Revascularisation of infra-popliteal arteries is mainly indicated in CLI patients. Technical innovations such as the introduction of dedicated long low-profile balloons and novel guidewire technology have facilitated endovascular therapy of complex below-the-knee lesions. It is of note that endovascular revascularisation in CLI is not limited to infra-popliteal revascularisation. It was shown that multilevel revascularisation is required in a substantial subset of CLI patients [8181. Graziani L, Silvestro A, Bertone V, Manara E, Andreini R, Sigala A, Mingardi R, De Giglio R. Vascular involvement in diabetic subjects with ischemic foot ulcer: a new morphologic categorization of disease severity. Eur J Vasc Endovasc Surg. 2007;33:453-60. ].

Endovascular therapy is advantageous over bypass surgery in CLI patients in whom no pedal runoff is visible and thus no bypass option is present ( Figure 5A, Figure 5B, Figure 5C). Restoration of straight-line flow to the pedal arch by angioplasty of one or more tibial arteries is required for clinical success. In most cases, below-the-knee obstructions can be treated using an ipsi-lateral antegrade approach. In the case of obstructive involvement of the iliac or proximal femoral arteries, intervention can be performed using cross over technique. Technical success of infra-popliteal artery PTA is > 90% [2121. Bosiers M, Peeters P, D’Archambeau O, Hendriks J, Pilger E, Duber C, Zeller T, Gussmann A, Lohle PN, Minar E, Scheinert D, Hausegger K, Schulte KL, Verbist J, Deloose K, Lammer J. AMS INSIGHT -absorbable metal stent implantation for treatment of below-the-knee critical limb ischemia: 6-month analysis. Cardiovasc Intervent Radiol. 2009;32:424-35. ]. The use of a retrograde approach is known to increase the rate of procedural success in infrapopliteal interventions, with reported limb salvage rates at 12 months between 64 % and 82.3 % after retrograde pedal access interventions [8282. Mustapha JA, Saab F, McGo T, Heaney C, Diaz-Sandoval L, Sevensma M, Karenko B. Tibio-pedal arterial minimally invasive retrograde revascularization in patients with advanced peripheral vascular disease: the TAMI technique, original case series. Catheter Cardiovasc Interv 2014;83:987-94. ]. Nevertheless, restenosis rates after infra-popliteal balloon angioplasty are higher compared to those after femoropopliteal revascularisation [8383. Romiti M, Albers M, Brochado-Neto FC, Durazzo AE, Pereira CA, De Luccia N. Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia. J Vasc Surg. 2008;47:975-81. ]. It appears that restenosis rates are directly proportional to lesion length [2121. Bosiers M, Peeters P, D’Archambeau O, Hendriks J, Pilger E, Duber C, Zeller T, Gussmann A, Lohle PN, Minar E, Scheinert D, Hausegger K, Schulte KL, Verbist J, Deloose K, Lammer J. AMS INSIGHT -absorbable metal stent implantation for treatment of below-the-knee critical limb ischemia: 6-month analysis. Cardiovasc Intervent Radiol. 2009;32:424-35. , 8484. Rand T, Basile A, Cejna M, Fleischmann D, Funovics M, Gschwendtner M, Haumer M, Von Katzler I, Kettenbach J, Lomoschitz F, Luft C, Minar E, Schneider B, Schoder M, Lammer J. PTA versus carbofilm-coated stents in infrapopliteal arteries: pilot study. Cardiovasc Intervent Radiol. 2006;29:29-38. , 8585. Soder HK, Manninen HI, Jaakkola P, Matsi PJ, Rasanen HT, Kaukanen E, Loponen P, Soimakallio S. Prospective Trial of Infrapopliteal Artery Balloon Angioplasty for Critical Limb Ischemia: Angiographic and Clinical Results. J Vasc Interv Radiol. 2000;11:1021-31. , 8686. Schmidt A, Ulrich M, Winkler B, Klaeffling C, Bausback Y, Braunlich S, Botsios S, Kruse HJ, Varcoe RL, Kum S, Scheinert D. Angiographic patency and clinical outcome after balloon-angioplasty for extensive infrapopliteal arterial disease. Catheter Cardiovasc Interv. 1;76(7):1047-54 ]. Of note, vessel sizing and consequent device choice should be considered a relevant matter. As known, the lumen size detected by angiography usually tends to cause undersizing of the balloon diameter, particularly in BTK vessels, which often have a large burden of atherosclerosis [9393. Danielsson G, Albrechtsson U, Norgren L, Danielsson P, Ribbe E, Thorne J, Zdanowski Z. Percutaneous transluminal angioplasty of crural arteries: diabetes and other factors influencing outcome. Eur J Vasc Endovasc Surg. 2001;21:432-6. ]. In this context, the use of intravascular ultrasound might be helpful to ensure correct sizing of the balloon used according to the real vessel diameter ( Figure 5D).

On the other hand, in contrast to angiographic outcomes, limb salvage rates subsequent to endovascular and surgical BTK revascularisation have been studied extensively. It is of note that patency rates subsequent to endovascular below-the-knee (BTK) revascularisation are significantly lower compared to those after bypass surgery [8787. Albers M, Romiti M, De Luccia N, Brochado-Neto FC, Nishimoto I, Pereira CA. An updated meta-analysis of infrainguinal arterial reconstruction in patients with end-stage renal disease. J Vasc Surg. 2007;45:536-42. ]. However, limb salvage rates are not different comparing endovascular and surgical revascularisation, indicating that arterial patency after endovascular therapy is not the only factor affecting limb salvage. Whilst increased perfusion is required for ulcer healing in CLI, maintenance of lower extremity skin integrity may be observed despite arterial re-obstruction [8888. Ferraresi R, Centola M, Ferlini M, Da Ros R, Caravaggi C, Assaloni R, Sganzaroli A, Pomidossi G, Bonanomi C, Danzi GB. Long-term outcomes after angioplasty of isolated, below-the-knee arteries in diabetic patients with critical limb ischaemia. Eur J Vasc Endovasc Surg. 2009;37:336-42. , 8989. Faglia E, Dalla Paola L, Clerici G, Clerissi J, Graziani L, Fusaro M, Gabrielli L, Losa S, Stella A, Gargiulo M, Mantero M, Caminiti M, Ninkovic S, Curci V, Morabito A. Peripheral angioplasty as the first-choice revascularization procedure in diabetic patients with critical limb ischemia: prospective study of 993 consecutive patients hospitalized and followed between 1999 and 2003. Eur J Vasc Endovasc Surg. 2005;29:620-7. ]. Thus, functional lower limb outcomes are substantially better as compared to arterial patency rates in CLI patients undergoing endovascular revascularisation.

Long and very calcified occlusions and poor pedal runoff are predictors for poor technical and clinical success of below-the-knee angioplasty [11. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5-S67.
Although partly outdated with regard to technical possibilities in endovascular therapy for PAD, these are the most updated version of the international TASC guidelines., 9090. Aulivola B, Gargiulo M, Bessoni M, Rumolo A, Stella A. Infrapopliteal angioplasty for limb salvage in the setting of renal failure: do results justify its use?. Ann Vasc Surg. 2005;19:762-8. , 9191. Gargiulo M, Maioli F, Ceccacci T, Morselli-Labate AM, Faggioli G, Freyrie A, Giovanetti F, Testi G, Muccini N, Stella A. What’s next after optimal infrapopliteal angioplasty?. Clinical and ultrasonographic results of a prospective single-center study. J Endovasc Ther. 2008;15:363-9. , 9292. Gargiulo M CT, Faggioli GI. Outcome and prognostic factors of peroneal artery transluminal angioplasty in critical limb ischemia. J Endovasc Ther. 2007;14:SupplII-I10-I1. , 9393. Danielsson G, Albrechtsson U, Norgren L, Danielsson P, Ribbe E, Thorne J, Zdanowski Z. Percutaneous transluminal angioplasty of crural arteries: diabetes and other factors influencing outcome. Eur J Vasc Endovasc Surg. 2001;21:432-6. ]. Stent implantation in infrapopliteal arteries should be limited to recoil and any post-procedural complications (thrombosis, flow-limiting dissections). In this specific situation, drug-eluting stents have been shown to be superior compared to bare metal stents [9494. Siablis D, Karnabatidis D, Katsanos K, Kagadis GC, Kraniotis P, Diamantopoulos A, Tsolakis J. Sirolimus-eluting versus bare stents after suboptimal infrapopliteal angioplasty for critical limb ischemia: enduring 1-year angiographic and clinical benefit. J Endovasc Ther. 2007;14:241-50. ].

Pedal bypass grafting (preferably with autologous vein) is indicated in CLI patients with long occlusions of tibial arteries or tibial lesions unsuitable for endovascular therapy. This technique is safe, effective and its durability is better as compared to endovascular revascularisation [8383. Romiti M, Albers M, Brochado-Neto FC, Durazzo AE, Pereira CA, De Luccia N. Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia. J Vasc Surg. 2008;47:975-81. ]. However, as outlined above, limb salvage rates are not higher compared to those after endovascular revascularisation [8383. Romiti M, Albers M, Brochado-Neto FC, Durazzo AE, Pereira CA, De Luccia N. Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia. J Vasc Surg. 2008;47:975-81. ].

In a proportion of patients not amenable for classical revascularization techniques (no-option patients), who showed amputation and death rates as high as 20% [9595. Abu Dabrh AM, Steffen MW, Undavalli C, Asi N, Wang Z, Elamin MB, Conte MS, Murad MH. The natural history of untreated severe or critical limb ischemia. J Vasc Surg. 2015 Dec;62(6):1642-51.e3 ] venous arterialization is becoming an alternative approach to improve limb salvage rates. Two major techniques are currently performed in clinical practice: the hybrid technique and a totally percutaneous technique. The former one includes a bypass with a proximal surgical arteriovenous anastomosis and an endovascular treatment of the venous valves and the collaterals distal to the anastomosis in order to achieve direct blood flow to the anterior vein plexus of the foot. The percutaneous technique is performed with dedicated tools which allow the operator to craft an artero-venous fistula in the proximal segment of the leg, while the deep vein distal to the anastomosis is enclosed with a covered stent down to the ankle. Finally, a dedicated valvulotomy system breaks vein valves in the deep plantar veins allowing flow to the anterior venous plexus of the foot. While the path towards wide standardization of these techniques is still far away, in highly selected patients they may represent the only valuable option to avoid primary amputation.

Post-procedural treatment

After surgical or endovascular limb revascularisation, adjunctive medical therapy is required. Antiplatelet agents must be prescribed indefinitely in all patients undergoing lower limb revascularisation.

Within the CASPAR study (clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease) no significant benefit of dual antiplatelet therapy was shown for patients undergoing below-the-knee bypass using both prosthetic grafts and venous conduits [9696. Belch JJ, Dormandy J, Biasi BM, Cairols M, Diehm C, Eikelboom B, Golledge J, Jawien A, Lepantalo M, Norgren L, Hiatt WR, Becquemin JP, Bergqvist D, Clement D, Baumgartner I, Minar E, Stonebridge P, Vermassen F, Matyas L, Leizorovicz A. Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. J Vasc Surg. 52:825-33, 33 e1-2 ]. In a subgroup analysis however, use of dual antiplatelet therapy was associated with significant benefits in patients treated with prosthetic grafts. Considering the lack of randomised data assessing the effect of dual antiplatelet therapy subsequent to endovascular therapy and extrapolating results from coronary intervention [9797. Mehta S, Yusuf S, Peters R, Bertrand M, Lewis B, Natarajan M, Malmberg K, Rupprecht H-J, Zhao F, Chroalvicius S, Copland I, Fox K. Effects of pretreatment with Clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;18:527-33. ] dual antiplatelet therapy over 1 month is recommended, especially in conjunction with the application of stents or drug-coated balloons.

In patients with bypass at high risk of thrombosis (poor runoff, vein bypass with suboptimal graft or arterial flow velocities <0.4 m/s in the bypass) anticoagulation may be considered.

Considering the risk of restenosis both endovascular and surgical revascularisation, regular clinical and haemodynamic follow-up is mandatory in patients with CLI. Clinical outcomes are improved if repeated revascularisations are performed [1414. Dick F, Diehm N, Galimanis A, Husmann M, Schmidli J, Baumgartner I. Surgical or endovascular revascularization in patients with critical limb ischaemiaischemia: influence of diabetes mellitus on clinical outcome. J Vasc Surg. 2007;45:751-61.
Interesting article describing interdisciplinary experiences in CLI patients.].

PRIMARY AMPUTATION

Primary amputation is defined as major amputation (i.e., an amputation above the ankle) without an antecedent attempt at revascularisation. It is proposed only in CLI patients unsuitable for any form of revascularisation or medical therapy. Preservation of the knee joint and a significant length of the tibia permit the use of lightweight prostheses. Consequently the lowest level of amputation that will heal is the ideal site for limb transaction.

Acute limb ischaemia

Acute limb ischaemia (ALI) is defined as a sudden decrease in arterial lower limb perfusion with a substantial risk of limb loss. The most frequent causes are arterial embolisation (heart disease, arterial atheroma or arterial aneurysm) and thrombosis (peripheral arterial aneurysm, arterial dissection or atherosclerotic plaque rupture). Patient history and physical examination often elucidate the cause of the acute lower limb ischaemia. At physical examination, the findings of acute limb ischaemia may include “5Ps” in the ischaemic limb: pain, pulselessness, pallor, paresthaesia (abnormal sensitivity) and paralysis.

In ALI the clinical presentation of sensory loss and paralysis of the lower extremity directly impacts on the prognosis. ALI is clinically classified based on limb viability in 3 categories:

• Category I: presence of vital signs of the limb (no sensory loss or muscle weakness).
• Category II: risk of impending limb loss (moderate sensory loss associated with rest pain, mild to moderate muscle weakness).
• Category III: irreversible damage of nerve/muscle structures (major tissue loss or permanent nerve damage with profound sensory loss and paralysis).

The diagnosis of ALI is primarily clinical. In addition, duplex sonography or other imaging options such as computed tomography or angiography are required to define the anatomic level and to plan arterial revascularisation. Prompt reconstitution of arterial perfusion is the most effective treatment aimed at maintaining a viable limb. The first treatment goal is to prevent thrombosis propagation by intravenous administration of heparin. Assessment of the aetiology of ALI allows for a selection of the most appropriate therapy (endovascular therapy, thrombolysis or open surgery). Arterial revascularisation is proposed for ALI patients in category I and II, while primary major amputation is indicated for patients in category III. Technical developments, including percutaneous aspiration thrombectomy, percutaneous mechanical thrombectomy and intra-arterial lysis, have recently facilitated endovascular therapy for ALI [9898. Diehm N, Schillinger M, Minar E, Gretener S, Baumgartner I. TASC II section E3 on the treatment of acute limb ischemia: commentary from European interventionists. J Endovasc Ther. 2008;15:126-8. ]. In contrast, standard surgical techniques include the use of the Fogarty catheter which requires intraoperative angiography to document technical success. Moreover, severe ALI may require fasciotomy including all lower limb compartments.

Conclusion

Peripheral arterial occusive disease is a relevant aspect of cardiovascular morbidity due to its effect on patients’ quality of life and its impact on public health costs. In the modern era of personalized medicine interventional cardiologists are required to offer their patients both behavioural and pharmacological tools to reduce the global burden of peripheral disease as well as the ability of using advanced technical skills to obtain effective and durable revascularization. Although clinical scenarios are often different and progressively more complex, therapeutic goals should be individualized and always incorporated in a wider evaluation of global cardiovascular risk profile.

Personal perspective - Alberto Cremonesi

The interest of vascular physicians for percutaneous treatment of PAD disease is growing. It is well recognized that the attention of cardiologists and other vascular specialists to PAD detection and treatment is increasing. Endovascular interventions have greatly changed the therapeutic landscape allowing for less invasive treatment options and are today, considered the first-line revascularisation approach for most PAD patients. Actually, endovascular procedures are less invasive and offer the advantage of being endlessly repeatable. From this perspective, the use of drug-eluting balloons might be helpful in improving patients’ quality of life and reducing hospitalization costs for recurrent admissions. Their association with mortality was not confirmed as causative and they should not been taken out of cath lab shelves until proven evidence is provided about paclitaxel toxicity. In the meantime, novel stents and plaque modification devices are now available to achieve a better and more durable result after femoropopliteal angioplasty.

Although resources are still limited and require to be optimally used, a tailored approach should be pursued in each patient as the milestone of endovascular medicine in the present and future treatment of PAD disease.