Peripheral Arterial Disease: Management in 2016 · Peripheral Arterial Disease: Management in 2016 ... Hirsch et al. Circulation. 2006;113 ... • Neither strength training nor upper

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Peripheral Arterial Disease: Management in 2016

Shant M. Vartanian, MDAssistant Professor of Surgery

Division of Vascular and Endovascular Surgery

Disclosures

I have nothing to disclose

• Atherosclerosis of the non-cardiac vessels

• Atheroprone areas• Aortic bifurcation• Common femoral artery• Hunters canal• Tibioperoneal vessels

• An ankle-brachial index (ABI) ≤0.90 is sensitive and specific for arterial stenosis/occlusion and diagnostic for PAD

• Sensitivity 80-95%• Specificity >95%

Definition

• Estimated > 200 million people worldwide with PAD• Worldwide prevalence between 3-12%• Disproportionally affecting low and middle income regions

Worldwide Prevalence

Bloor K. Natural History of Arteriosclerosis of the Lower Extremities.

Ann R Coll Surg Engl. 1961 Jan;28(1):36-52.2

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Epidemiology

Fowkes FGR et al. Nat Rev Cardiol. Nature Research; 2016 Nov 17.

• 30% increase over previous decade

• Groups at highest risk• Age ≥70 years• Age 50 to 69 years with a history of smoking or diabetes• Age 40 to 49 with diabetes and at least one other risk factor for

atherosclerosis

• Other risk factors• Male gender• Black ethnicity• Family history of atherosclerosis• Smoking • Hypertension• Hyperlipidemia• Homocysteinemia

Risk Factors

Hirsch et al. Circulation. 2006;113(11):e463.

Risk Factors

Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). 2007. pp. S5–67.

• 1999–2000 National Health and Nutrition Examination Survey• 2174 participants from cohort of 9000+ that had ABI data• Prevalence in patients > age 40 ~5%

Prevalence by Age

Selvin, and Thomas P. Erlinger Circulation. 2004;110:738-743 1555.

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• Asymptomatic• 3x more common than symptomatic PAD

• Claudication• Reproducible discomfort in a specific muscle group that is

induced by exercise and then relieved with rest.

• Limb threatening ischemia• AKA “Critical Limb Ischemia”

Peripheral Arterial Disease Systemic Atherosclerosis


• ABI predicts future death and cardiovascular events

Asymptomatic PAD


• ABI predicts future death and cardiovascular events

Abnormal ABI and Risk Prediction

Fowkes et al. JAMA, 300 (2008), pp. 197–208

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• Shaded values (number of patients) reflect those that should have FRS reclassified when factoring in ABI

• Reclassification in 19% of men and 36% of women

Abnormal ABI and Risk Prediction

Fowkes et al. JAMA, 300 (2008), pp. 197–208

Screening for Asymptomatic PAD

Alahdab et al. J Vasc Surg. 2015 Mar;61(3 Suppl):42S-53S.


Lin et al. Ann Intern Med, 159 (2013), pp. 333–341

• US Preventative Services Task Force

• Accurate test available• ABI sensitive and specific except in non-compressible vessels

• Disease is sufficiently prevalent with significant morbidity• All cause and CV mortality increase 2-3 fold

• Screening leads to reduced morbidity and mortality• Minimal data

• Treatment of screening-detected individuals reduces morbidity and mortality

• Minimal data• Screening is not harmful and is cost effective


Lin et al. Ann Intern Med, 159 (2013), pp. 333–341

• US Preventative Services Task Force

• Conclusion• Indeterminate rating for screening ABI

• Interpretation• ABI testing may incrementally improve cardiovascular risk

prediction

• Targeted subgroups, particularly those not yet on cardioprotective treatment regimens, are most likely to benefit PAD screening as it should trigger more aggressive medical management

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• ABI is the first line, non-invasive test to establish diagnosis of PAD

• Screening with ABI in absence of risk factors for PAD is not recommended

• Screening ABI is reasonable if results will improve risk stratification, preventative care and medical management in high risk groups

•Age > 70•Smokers•Diabetics

• May be incremental value of adding ABI to traditional risk assessment tools (Framingham Risk Score)

Summary of Recommendations for Asymptomatic PAD





Peripheral Arterial Disease

• Reproducible onset• Quickly relieved with rest• No effect by position

• Calf claudication• Most common• Cramping, aching discomfort

• Thigh or buttock claudication• Cramping, aching thigh or buttock pain• Hip pain• Impotence common• May have palpable pedal pulses with isolated iliac disease

• Foot claudication• Severe foot arch pain with exertion• Often with numbness

Clinical Features of Claudication Pseudoclaudication SyndromesCondition Location Characteristic Effect of exercise Effect of rest Effect of position Other

characteristicChronic compartment syndrome

Calf muscles Tight, bursting pain

After much exercise (jogging)

Subsides very slowly Relief with elevation Typically heavy muscled athletes

Venous claudication

Entire leg, worse in calf

Tight, bursting pain

After walking Subsides slowly Relief speeded by elevation

History of iliofemoral deep vein thrombosis, signs of venous congestion, edema

Nerve root compression

Radiates down leg

Sharp lancinating pain

Induced by sitting, standing, or walking

Often present at rest

Improved by change in position

History of back problems. Worse with sitting. Relief when supine or sitting. Not intermittent

Symptomatic Baker cyst

Behind knee Swelling, tenderness

With exercise Present at rest None Not intermittent

Hip arthritis Lateral hip, thigh

Aching discomfort

After variable degree of exercise

Not quickly relieved Improved when not weight bearing

Symptoms variable. History of degenerative arthritis

Spinal stenosis Often bilateral buttocks, posterior leg

Pain and weakness

May mimic IC Variable relief but can take a long time to recover

Relief by lumbar spine flexion

Worse with standing and extending spine

Foot/ankle arthritis

Ankle, foot, arch

Aching pain After variable degree of exercise

Not quickly relieved May be relieved by not bearing weight

Variable, may relate to activity level and present at rest

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• Broad range of ABI in relation to degree of functional impairment

Diagnostic Testing• Broad range of ABI in relation to degree of functional impairment

• Exercise ABI to discriminate IC from neurogenic causes• No standardized protocol• Treadmill test w/ predetermined speed x 5 min• 2 min calf raises

• Anatomic imaging (ultrasound, CT or MR) reserved for patients being considered for revascularization

Diagnostic Testing

• 1508 patients with claudication seen from 1947 – 1953• Most diagnosed with angiography• Seen every 3 months with treadmill walking test• No patients treated surgically• Diabetes in 4%

Natural History of Claudication

Bloor K. Natural History of Arteriosclerosis of the Lower Extremities.

Ann R Coll Surg Engl. 1961 Jan;28(1):36-52.2

• Improved 55% Stable 35% Worse 10%• Benefit persist over 5 years for those that live that long• Death in 673

• 60% of mortality due to cardiac disease

Natural History of Claudication

Bloor K. Natural History of Arteriosclerosis of the Lower Extremities. Ann R Coll Surg Engl. 1961 Jan;28(1):36-52.2

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• Fate of the patient > Fate of the limb

• Heavy burden of systemic atherosclerosis• Morbidity and mortality due to CV events

• Decreased limb function translates into impaired quality of life

• In non-diabetic, non-ESRD, rarely progresses to limb threat

• Risk reduction• Functional improvement

Goals of Therapy• Smoking cessation• Treatment of dyslipidemia• Diabetes

• ~30% of diabetics have manifestations of PAD• Hypertension

• No evidence that treatment of HTN worsens functional outcomes

• Antiplatelet therapy• Single agent antiplatelet therapy

• Homocysteine-lowering drugs• 30% of patients with known PAD have elevated serum levels of

homocysteine• Two prospective trials evaluating homocysteine lowering drugs in

reducing CV events in PAD patients

Risk Reduction

• Goal of functional improvement in the limb

• FDA approved with indication for PAD• Cilostazol• Pentoxifylline

• Available in Europe• Naftidrofuryl

Pharmacotherapy for Functional Improvement

• Pentoxifylline (Trental)• FDA approved in 1984• Mechanism: Reducing blood viscosity and retarding platelet

aggregation• Dosing: Start at 400mg tid and can be titrated up to 1800

mg/day • Side effects of nausea, headache, drowsiness, and anorexia• HTN can worsen on medication

• Initial multicenter, blinded placebo control trial showed improved pain-free and maximal walking distance compared to placebo

• Modest effect: Multiple studies have failed to show improved ABI (both resting and exercise) on therapy

Pharmacotherapy: Pentoxifylline

Porter et al. Am Heart J 1982;104:66-72.

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• Cilostazol (Pletal)• Mechanism: phosphodiesterase inhibitor and direct

vasodilator• Dosing: 100mg bid• Contraindicated in any degree of heart failure• Side effects: headaches, palpitations, edema

• Improvement in maximal and pain-free walking distance in as short as 4 weeks

Pharmacotherapy: Cilostazol

Robless P et al. Cilostazol for peripheral arterial disease. Cochrane Database Syst Rev 2008;(1):CD003748.

• Randomized, double blind, placebo controlled trial of pentoxifylline vs cilostazol in claudication

• 698 patients randomized• Treadmill testing up to 6 months

Pharmacotherapy Trials

Dawson et al. The American Journal of Medicine, Volume 109, Issue 7, 2000, 523–530

• Ramipril• Randomized, double blind, placebo controlled trial • 212 patients received 10mg/day x 24 weeks• 10 mg/d for 24 weeks• Significant improvements in pain-free and maximal treadmill

walking times• Consider ace inhibitor as first line agent in treatment of HTN

in patients w/ PAD• Naftidrofuryl Oxalate

• Enhancing aerobic glycolysis and oxygen consumption in ischemic tissues

• Not FDA approved• It has been shown to increase pain-free walking distance

Pharmacotherapy: Other Agents

Ahimastos AA et al. JAMA 2013;309: 453-60.

• Mechanism of action likely biochemical and biomechanical• Enlargement of existing collateral vessels• Exercise induced angiogenesis• Enhanced nitric oxide (NO) endothelium-dependent

vasodilatation of themicrocirculation• Improved bioenergetics of skeletal muscle• Improved hemorrheology

• Improvement in biomechanical measures even without improvement in resting ABI

• Can expect improvement in walking ability of 50% - 200% with improvements maintained for up to 2 years

Exercise Therapy

Watson et al. Cochrane Database Syst Rev 2008;(4)

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• Walking is the best modality• Superior to cycling, stair climbing, tiptoe raises, dancing, and

static or dynamic leg exercises• Neither strength training nor upper extremity aerobic exercise

appear to augment responses to walking• Low intensity = High intensity

• Walking session must be > 30 min and > 3x per week• Duration of program > 26 weeks

• Structured, supervised programs show best results

Exercise Program Components


• Poorly adhered to by patients• Low compliance and high drop out rate

• Claudication often coexists with comorbid conditions that preclude active participation (angina, heart failure, COPD, arthritis)

• Supervised exercise programs are the most effective and best studied form of exercise therapy but many U.S. insurance carriers do not currently provide benefits for participation in such programs

Exercise Therapy


• Fate of the limb• Benign nature of disease

• Functional impairment and effects on activities of daily living, occupation and quality of life

• Sense of disability in claudication correlates poorly with both physiologic testing and anatomic findings

• Interventions for claudication are done to improve function in the setting of significant ongoing disability in an active person

Revascularization for Claudication

Conte et al. J Vasc Surg. 2015 Jan 28.

• Clinical response to non-interventional therapies

• Expected functional benefits for the patient• Interventional treatment may provide no benefit in patients

with structural heart disease or lung disease

• Weighing the potential risks • Understanding the anatomy, interventional options, risks and

expected durability of intervention• Technical factors that predict interventional success

• Durable benefit at low risk is required to justify invasive vascular treatment


Conte et al. J Vasc Surg. 2015 Jan 28.

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Norgren L, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007 vol(45)pp. S5–67.

OMT, Exercise and Interventional Rx

Frans FA et al. Br J Surg; 2012 Jan;99(1):16–28.

• 9 randomized controlled trials comparing supervised exercise program vs. revascularization for claudication

• Aortoiliac and femorpopliteal disease• Varying degrees of optimal medical therapy• Balloon angioplasty +/- stent• Hemodynamic and functional testing

• Greater short-term benefit from PTA than exercise therapy but this was not sustained after 1 – 2 years

• Some trials showed longer walking distances in non-interventional arm at 2 years


Frans FA et al. Br J Surg; 2012 Jan;99(1):16–28.

• CLEVER study• Randomized 111 patients with aortoiliac disease to:

• Optimal medical therapy (OMT)• OMT + supervised exercise• OMT + stent revascularization

• Primary endpoint was peak walking time by treadmill test

• Secondary endpoints was community podometer, QOL


Murphy TP et al. J Am Coll Cardiol. 2015 Mar 17;65(10):999–1009.

• Supervised exercise has persistent benefit at 1 year beyond when formal SE had ended

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Summary of Recommendations for Claudication

• Optimal medical therapy for risk reduction• Smoking cessation• Statin therapy• Hgb A1c < 7.0%• HTN

• Consider Ramipril given functional improvement• Single agent antiplatelet therapy

• Pharmacotherapy for functional outcomes• In patients without heart failure, 3 month trial of cilostazol to

improve pain free walking

Summary of Recommendations for Claudication

• Supervised exercise program is 1st line treatment of claudication• > 30 min per session at least 3x / week• Duration of treatment > 12 weeks

• Home based program if supervised program is unavailable

• Revascularization for IC reserved for active patients with favorable risk benefit profile and who have failed non-invasive treatment

• Revascularization only if a reasonable likelihood of sustained benefit (>50% likelihood of clinical efficacy for at least 2 years)





Peripheral Arterial Disease• Clinical presentation

• Rest pain• Dependent rubor

• Ischemic ulceration• Often hidden between toes

• Gangrene

• Hemodynamic diagnostic criteria• Rest pain

• Ankle pressure < 50 mmHg• Toe pressure < 30 mmHg

• Tissue loss• Ankle pressure < 70 mmHg• Toe pressure < 50 mmHg

Critical Limb Ischemia

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Critical Limb Ischemia

• Annual mortality of 10-15%

Natural History of CLI

• Natural history• Unremitting pain• Non healing wounds• Loss of ambulatory function• Recurrent infections

• Major adverse limb events (any above ankle amputation or major revascularization) approaches 20% in the first year after an intervention

• Treatment options:• Effective Revascularization• Palliative wound care• Amputation

Fate of the Limb• General health of the patient• Age, comorbidities, ambulatory status

• Foot: likelihood of functional salvage• Severity of limb ischemia

• Anatomic distribution of disease

• Prior vascular interventions

• Availability of autogenous vein for LEB• Prosthetics and other non-autogenous conduits inferior

Revascularization in CLI

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• High quality imaging for planning• Digital angiography with dedicated, multiple views of ankle

and foot required

• Restore straight-line flow to the foot• Especially in cases with tissue loss• Pulsatile flow• Treating proximal lesions in the setting of a distal occlusion

will be inadequate for wound healing

• Surveillance and vigilant follow up• Clinical exam and duplex US• Low threshold for re-intervention

Revascularization in CLI Revascularization in CLI

◆Surgical Risk

◆Life Expectancy

◆Severity of Ischemia

◆Anatomy

◆Vein availability

◆Average (<5% mort)

◆≥ 2 years

◆Major tissue loss

◆Multi-level, TASC D

◆GSV or good alternate

◆High

◆Limited

◆Minor ulcer

◆Single level, TASC A-C

◆Inadequate

BYPASS FAVORED ENDO FAVORED

A Selective Revascularization Strategy Classification Schemes

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• Rutherford system never intended to be applied to diabetics

• By definition, Category 6 is “not salvageable”

• Heterogeneous nature of wounds, yet almost all are classified into Category 5

• Inability to relate coexisting infection

Classification Schemes

• Neuropathy • Loss of protective sensation• Imbalance develops between muscular flexors and extensors

• Resulting deformities, commonly at high pressure, weight-bearing surfaces

• Ulceration and loss of barrier function of the skin

• Amputations in diabetics correlate directly with the presence and severity of infection, more so than the relative contribution of wound characteristics and the presence of arterial disease

Pathophysiology of Limb Loss in Diabetes

• Society of Vascular Surgery proposal

• Lower Extremity Threatened Limb Classification System

• Aka “SVS WIfI”

• Classifies limbs by estimated the risk of amputation at 1 year, from very low (stage 1) to high (stage 4).

• Each stage is a composite of 3 elements:• Ischemia • Infection • Wound extent.

Threatened Limb Classification System

• Individual scoring systems previously validated

• Infection score = IDSA scoring system

• Wound score = PEDIS diabetic ulceration

• Ischemia score based on standard hemodynamic scale


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Mills JL et al. J Vasc Surg 2014. pp. 220–34.e1–2.

• Retrospectively validated by a number of centers• Accurately predicts amputation risk• Better risk stratification for Rutherford Cat 5• Correlates with duration of hospital stay and wound healing

rates

• Being applied to national quality improvement registry (VQI)

• Framework for better assessment of treatment strategies in CLI

WIFI Validation

• Severe consequences for both the patient and the limb

• 10-15% annual mortality• 10-20% annual rate of amputation if untreated

• Only effective treatment is revascularization

• New classification system (SVS WIFI) to supplant Rutherford

• Better risk prediction, especially in diabetes

Summary of CLI Questions?

Documents

Peripheral Arterial Disease: Management in 2016 · Peripheral Arterial Disease: Management in 2016 ... Hirsch et al. Circulation. 2006;113 ... • Neither strength training nor upper