Advances in theMedical Management of

Peripheral Arterial DiseaseWarner P. Bundens, MD, MS

Associate Clinical Professor of SurgeryAssociate Clinical Professor of Family and

Preventive MedicineSchool of Medicine

University of California, San DiegoLa Jolla, California

Key Question

How many of your patients with CV risk do

you test for peripheral arterial disease?

1. 0%-24%

2. 25%-50%

3. 51%-75%

4. 76%-100%

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Faculty Disclosure

Dr Bundens: grants/research support: sanofi-aventis Group.

Learning Objectives

Describe the prevalence and disease burden of PAD

State medical treatments for improving leg symptoms of the patient with PAD

Discuss interventions used to prevent systemic complications in the patient with PAD

PAD = peripheral arterial disease.

Peripheral Arterial Disease: What Is It?

PAD

PAOD

PAOD = peripheral arterial obstructive disease.

Lesions

What Is It?

ObstructedLumen

Plaque

Who Gets It?

PAD: Risk Factors Age

Uncommon: <50 years old50-70 years old

10% overall

20% with history of smoking or diabetes>70 years old

20%

Who Gets It?

PAD: Risk Factors Age Diabetes 4× Smoking 3.5×

Past or present Hypertension 2× Hyperlipidemia 0.1×

How Do You Diagnose It?

PAD Symptoms May be asymptomatic Claudication

Claudication

A Reproducible and

Consistent Symptom

Claudication

Muscular pain brought on by activity (walking) that is relieved by stopping that activity

Claudication

Claudication

Muscular pain brought on by activity (walking) that is relieved by stopping that activityDoes not occur at rest Is not brought on by standing

Other Causes of Leg Pain: “Pseudoclaudication”

► Spinal stenosis

► Nerve root compression

► Arthritis/joint disease, especially the hip

► Compartment syndrome

► Venous claudication

► Symptomatic Baker’s cyst

How Do You Diagnose It?

PAD Symptoms May be asymptomatic Claudication Ischemic rest pain

Ischemic Rest Pain

Distal foot Worse at night Decreased by lowering foot

How Do You Diagnose It?

PAD Symptoms May be asymptomatic Claudication Ischemic rest pain Tissue loss, nonhealing lesions, gangrene

Arterial Ulcer/Gangrene

Not Arterial

Nocturnal Leg/Foot Cramps

PAD: Physical Findings

Pulses Pallor Dependent rubor Thick nails Hairlessness Tissue loss/ulcer/gangrene

PAD: Physical Findings

Poor Sensitivity and Specificity

for Mild-to-Moderate PAD

PAD: An Objective Test

Flow vs Pressure

Ohm’s Law

Electrical: E = I·RVoltage Drop = Current × Resistance

Fluids: P = F·RPressure Drop = Flow × Resistance

Ohm’s Law

Office Measurement ofthe Ankle-Brachial Index (ABI)

Right arm pressure

Pressure:Posterior tibial Anterior tibial

Pressure:Posterior tibialAnterior tibial

Left arm pressure

SupinePatient

Ankle Pressure

Posterior Tibial Anterior Tibial

Patient Must Be Supine

The ABI

Both ankle and brachial systolic pressures should be taken using a hand-held Doppler instrument

For arm and leg, use higher of 2 pressures

Ankle Systolic PressureBrachial Artery Systolic

Pressure

ABI =

The ABI

Right Arm 150 mm Hg

Right AT 68

Right PT 75

Left Arm 143

Left AT 120

Left PT 100

Right ABI = 75/150 = 0.50 Left ABI = 120/150 = 0.80

AT = anterior tibial; PT = posterior tibial.

What Do the Numbers Mean?

ABI Typical values

Normal = 1.25-0.9Claudication = 1.0-0.3Rest pain = <0.4Tissue loss = <0.3

ABI <0.90

95% Sensitive and 99% Specific for PAD

TASC Working Group. J Vasc Surg. 2000;31(1 suppl):S1-S296.

ABI: Occasional “Gray” Areas

ABI 1.0-0.9Most of these

people have PAD

ABI >1.0Most of these

people do not have PAD

ABI Workshops

Demonstrations available throughout the day

Further Noninvasive Testing

Segmental pressures Doppler waveforms Exercise test

Lower Extremity Arterial Exam

Further Testing

Relative 5-Year Mortality Rates

*American Cancer Society. Cancer Facts and Figures, 2000.Criqui MH et al. N Engl J Med. 1992;326:381-386.

818

2332

39

86

0

20

40

60

80

100

ProstateCancer*

Hodgkin'sDisease

BreastCancer*

PAD ColorectalCancer*

LungCancer*

Pat

ien

ts (

%)

PAD Is a Bad Disease

WHY ?

Key Question

Without intervention, what percentage of PAD patients will have an MI or stroke in the next 5 years?

1. 10%

2. 25%

3. 50%

4. 75%

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MI = myocardial infarction.

Clinical Outcomes in Patients With PAD

Adapted from Weitz Jl. Circulation. 1996;94:3026-3049.

PAD Patient

PAD outcomes

Nonfatal events

(MI/stroke) 20%

Mortality 30%

Worsening claudication

16%

Leg bypass surgery

7%

Major amputation

4%

Stable claudication

73%

(5-year outcomes)

Intermittent claudication

40%

Critical leg ischemia

10%

Asymptomatic 50%

Cardiovascular

morbidity/mortality

PAD and All-Cause Mortality*

*Kaplan-Meier survival curves based on mortality from all causes.†Large-vessel PADAdapted from Criqui MH et al. N Engl J Med. 1992;326:381-386.

1.00

0.75

0.50

0.25

0.00

0 2 4 6 8 10 12

Year

Su

rviv

al

Normal subjectsAsymptomatic LV-PAD†

Symptomatic LV-PAD†

Severe symptomatic LV-PAD†

Diagnosis

2 Problems

CardiovascularRisk

Leg Symptoms Claudication Rest Pain Tissue Loss

Treatment

Cardiovascular Risk Stop smoking

Program Toes vs cigarettes

Blood pressure control 140/90 mm Hg 130/80 mm Hg if patient has diabetes or renal disease

Lipid control LDL <100 mg/dL

Diabetes control HbA1C <7%

Antiplatelet medication

Treatment

Hirsch A et al. J Am Coll Cardiol, 2006;47:1239-1312.

Antiplatelet Medications

Aspirin

Key Question

What is the proper daily dose of aspirin for cardiovascular risk reduction?

1. 75 mg

2. 81 mg

3. 300 mg

4. 325 mg

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Aspirin 81 mg/d

Antiplatelet Medications

Aspirin Dosage

OR = odds ratio.Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86.

0 0.5 1.0 1.5 2.0

500-1500 mg 34 19

160-325 mg 19 26

75-150 mg 12 32

<75 mg 3 13

Any aspirin 65 23

Antiplatelet Better Antiplatelet Worse

Aspirin Dose No. Trials OR (%) OR

Antiplatelet Medications

Aspirin Dosage: Risk of Major Bleeding

Placebo+ Aspirin

Clopidogrel+ Aspirin

<100 mg 3.0% 1.9%

100-200 mg 3.4% 2.8%

>200 mg 4.9% 3.7%

Aspirin Dose

CURE Trial. Circulation. 2003;108:1682-1687.

Antiplatelet Medications

Aspirin81 mg

Clopidogrel 75 mg

Antiplatelet Medications

8.7%Overall RRR

(P = .045)*

Months of Follow-up

Cu

mu

lati

ve E

ven

t R

ate

(%)

0

4

8

12

16

0 3 6 9 12 15 18 21 24 27 30 33 36

Clopidogrel ASA

Median follow-up = 1.91 years

5.32%

5.83%

Subjects had a recent MI, recent ischemic stroke, or symptomatic PAD

(N = 19,185)

*ITT analysisASA= aspirin; CAPRIE = Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events;RRR = relative risk reduction.CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.

CAPRIEClopidogrel vs ASA: MI, Ischemic Stroke, or Vascular Death

Subgroup Analysis

CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.

-40 -30 -20 -10 0 10 20 30 40

Risk Reduction (%)

ASA Better Clopidogrel Better

Patient with stroke 6431

Patient with MI 6302

Patient with PAD 6452

All patients 19,185

No. Patients

CAPRIE

Leg Problems

AsymptomaticNo specific treatment

ClaudicationDo nothing

PAD Treatment

Clinical Outcomes in Patients With PAD

Adapted from Weitz Jl. Circulation. 1996;94:3026-3049.

PAD Patient

Cardiovascularmorbidity/mortality

Worsening claudication

16%

Leg bypass surgery

7%

Major amputation

4%

Nonfatal events

(MI/stroke) 20%

Mortality 30%

Critical leg ischemia

10%

Asymptomatic 50%

Stable claudication

73%

(5-year outcomes)

Intermittent claudication

40%

PAD outcomes

Leg Problems

Asymptomatic Claudication

Do nothingWalking program

Best are supervised

–Few programs available

–Rarely reimbursable by insurance

Most patients must do their own

PAD Treatment

Walking Program

RegularAt least 5×/week

Length40-60 min/d

Typical resultsDoubling of walking distance each year

ExcusesPain, hills, cold, heat, rain, etc.

Claudication Treatment

Walking Program

Additional benefitsGood for

Heart

Lungs

Weight loss

MusclesSee your neighborhoodSee new areasTheir dog will love it (if they have one)

Claudication Treatment

Walking Program

Avoid negative walking programsDisability parkingWheelchairsMotorized carts

Claudication Treatment

Walking Program

The Best Treatment, But Requires the Patient’s Commitment

Claudication Treatment

Leg Problems

AsymptomaticClaudication

Walking programDrugs: pentoxifylline; cilostazol

PAD Treatment

Cilostazol

Not a cure Average benefit

65% increase in maximum walking distance at 6 months Results not immediate Exact mechanism unknown Common side effects

Headache, diarrhea, ankle swelling, palpitations Contraindicated in patients with a history of congestive

heart failure Reduce dosage indicated with some concomitant

medications, eg, omeprazole, diltiazem

PAD Treatment

Asymptomatic Claudication

Walking program Drugs: pentoxifylline; cilostazol Invasive: angioplasty/stenting; surgery

Leg Problems

PAD Treatment

My Approach/Recommendations

ClaudicationWalking programDrug(s): cilostazol Invasive: angioplasty/stenting; surgery

Leg Problems

Asymptomatic Claudication Ischemic rest pain

Refer Nonhealing wounds/ulcers/tissue loss

Refer

PAD Treatment

Critical Limb Ischemia

These patients need revascularizationAngioplasty/stentingSurgery

If revascularization is not possibleMay need amputation

PAD Treatment

Case Study

Patient Case Study

Patient’s first visit to your practice because he is new to your area

58-year-old, male Occupation: “In sales” Complaint: “My leg hurts.” History of present illness

6-month history of right calf pain with walking

Pain begins at ~60 yards; patient has to stop at ~100 yards

Pain goes away within 1 minute of stopping and standing

No pain at rest

Patient Case Study

Medical historyNot on any medicationsOnce told his blood pressure was “a little high”Doesn’t know his cholesterol or diabetes statusHas only sought medical care for acute problems

in the past Smoking history

Smokes 1-2 packs/d × 35 years

Patient Case Study

Positive physical findingsRight arm systolic blood pressure: 160 mm HgLeft arm systolic blood pressure: 152 mm Hg Left carotid bruitAbsent right popliteal, PT, dorsalis pedis pulsesRight PT pressure: 80 mm HgRight AT pressure: 66 mm HgLeft PT pressure: 135 mm HgLeft AT pressure:140 mm Hg

AT = anterior tibial; PT = posterior tibial.

Patient Case Study

Right ABI = 80/160 = 0.50 Left ABI = 140/160 = 0.88 Has abnormal ABIs: both legs Only has symptoms in his right leg

Decision Point

What etiology might account for unilateralclaudication?

1. Vascular disease limited to one leg

2. Bilateral vascular disease worse in one leg causing symptoms to appear earlier in one leg than another

3. Peripheral neuropathy due to diabetes

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Patient Case Study

You tell the patient he has:PAD

A serious disease

– It is the cause of his walking problem

– It is also a marker for the systemic disease atherosclerosis and he is at risk for heart attack or stroke

Probable hypertension

Decision Point

What test(s) would you consider now?

1. Lipid, glucose, repeat ABI

2. Lipid, glucose, segmental pressures

3. Lipid, glucose, carotid duplex, and repeat blood pressure

4. Segmental pressures

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Patient Case Study

He needs further evaluationRepeat blood pressure checksBlood tests: lipid panel, glucoseCarotid duplex

He needs treatment for his cardiovascular risks

Patient Case Study

Treatment for his cardiovascular risksStop smoking: teach him how or referProbable blood pressure controlLipids?Diabetes?Antiplatelet therapy

Patient Case Study

He says: “I hear you. I know those things are important, but I

came in here for this right calf pain I get with walking. What can we do about that? I had a neighbor who had ‘the balloon treatment’ and he was cured.”

You may be thinking: “I’m trying to save his life.”

But unless you address his claudication, he may not come back and give you the chance

You may need to address the claudication first

Patient Case Study

You describe the treatment optionsWalking programDrug(s): cilostazol Invasive: angioplasty/stenting; surgery

Q & A

PCE Takeaways

PCE Takeaways

PAD is a common disease PAD is a serious disease

A marker for the systemic disease atherosclerosis Diagnosis usually is not difficult Management usually is straightforward

Key Question

Will you use ABI testing to diagnose patients

at risk for PAD?

1. Not likely

2. Somewhat likely

3. Very likely

4. Extremely likely

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