Sheraton Miami Mart Hotel

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2008
Symposia Series 1

• Sheraton Miami Mart Hotel
• Miami, Florida
• April 5, 2008

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Peripheral Arterial Disease Keeping Pace With
Current Diagnostic and Treatment Options

• Randall M. Zusman, MD
• Associate Professor of Medicine
• Harvard Medical School
• Director, Division of Hypertension and Vascular
  Medicine
• Massachusetts General Hospital
• Boston, Massachusetts

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Faculty Disclosure

• Dr Zusman advisory board/research
  grants/speakers bureau Bristol-Myers Squibb
  Company, Daiichi Sankyo, Forest Pharmaceuticals,
  Inc., Novartis, Pfizer Inc., sanofi-aventis

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Learning Objectives

• State the clinical manifestations of PAD
• Perform ankle-brachial index measurements in
  patients at risk for PAD
• Describe medical treatments for improving leg
  symptoms in patients with PAD

PAD peripheral arterial disease.
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PAD Prevalence in the
Primary Care Office Setting
NHANES1 Age gt40
4.3
The prevalence of PAD in primarycare clinics
was almostin high-risk patients
San Diego2 Mean age 66
11.7
30
NHANES1 Age 70
14.5
Rotterdam3 Age gt55
19.1
Diehm4 Age 65
19.8
PARTNERS5 Age gt70, or between 50-69 with history
of diabetes or smoking
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0
5
10
15
20
25
30
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NHANES National Health and Nutrition
Examination Survey PARTNERS PAD Awareness,
Risk, and Treatment New Resources for Survival
Program. 1. Selvin E, et al. Circulation.
2004110738-743 2. Criqui MH, et al.
Circulation.198571510-515 3. Meijer WT, et al.
Arterioscler Thromb Vasc Biol. 199818185-192 4.
Diehm C, et al. Atherosclerosis.
200417295-105 5. Hirsch AT, et al. JAMA.
20012861317-1324.
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What Is PAD?

• Atherosclerotic occlusion of the arteries to the
  legs
• PAD may be asymptomatic or present with atypical
  symptoms
• Common, but often overlooked
• Associated with significant morbidity and
  mortality

www.nhlbi.nih.gov/health/dci/Diseases/pad.
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VIDEO CLIP Predilation ArteriogramBilateral
Iliac Artery Stenosis Severe Aortic
Atherosclerosis

• Courtesy Michael R. Jaff, DO
• Director, Vascular Center
• Massachusetts General Hospital
• Boston, Massachusetts

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Predilation ArteriogramBilateral Iliac Artery
Stenosis Severe Aortic Atherosclerosis-VIDEO
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PAD Scope of the Problem

• Exact prevalence is unknown

Includes MI and angina pectoris. CHD coronary
heart disease MI myocardial infarction. AHA.
Heart Disease and Stroke Statistics2008 Update.
www.americanheart.org Hiatt WR. N Engl J Med.
20013441608-1621. .
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PAD increases the risk of CHD death by
approximately
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KEY QUESTION

• 1-2
• 3-4
• 5-6
• 6-7
• 7-8
• Use your keypad to vote now!

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PAD increases the risk of CHD death by
approximately

• 1-2
• 3-4
• 5-6
• 6-7
• 7-8

Use your keypad to vote now!
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PAD Increased Risk of Mortality
Patients with large-vessel PAD are at 6 the
risk of dying from CHD compared with patients
without PAD
10.0
8.0
6.6 (2.9-14.9)
6.0
Relative Risk of Death (95 CI)
4.0
3.1 (1.9-4.9)
2.0
0.0
Death From CHD
All-Cause Mortality
Cause of Death
ABI 0.8. ABI ankle-brachial index. Adapted
from Criqui MH, et al. N Engl J Med.
1992326381-386.
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Case Study
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Patient Profile
Scenario 1

• 58-year-old Latino male
• Presents to the clinic after referral from
  emergency department where he was evaluated and
  discharged after an episode of chest pain
• Coronary event ruled out by lab and diagnostic
  studies
• Construction worker with no health benefits

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Current History

• Complains of fatigue and inability to maintain
  current productivity at the work site
• Mild leg pain
• Remembers being told his sugar was a little
  high
• Reports he is not on any medications
• Reports he does not drink alcohol
• Smokes 1 pack/d x 30 years

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Physical Examination

• Results
• Height 5 ft 9 in
• Weight 190 lb
• BMI 28.1 kg/m2
• Waist circumference 40 in
• Blood pressure 130/85 mm Hg
• Pulse 72 bpm

BMI body mass index.
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Which element of the patients history creates
the highest index of suspicionfor PAD?
?
DECISION POINT

• Age
• Diabetes
• Ethnicity
• Hypertension
• Smoking
• Use your keypad to vote now!

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Which element of the patients history creates
the highest index of suspicionfor PAD?

• Age
• Diabetes
• Ethnicity
• Hypertension
• Smoking

Use your keypad to vote now!
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PAD Common Risk Factors
?Lesser risk
Greater risk ?
Diabetes
4.05
Smoking
2.55
Patients with diabetes are at a 4x higher risk
of developing symptomatic PAD versus the general
population
Hypertension
1.51
Total cholesterol (10 mg/dL)
1.10
0 1 2 3 4 5 6
Age gt40 years
PAD diagnosis based on ABI lt0.90. Newman AB, et
al. Circulation. 199388837-845.
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PAD Prevalence Increases With Age
Rotterdam Study (ABI lt.9) San Diego
Study (PAD by noninvasive tests)
60
50
40
Patients With PAD ()
30
20
10
0
55-59
60-64
65-69
70-74
75-79
80-84
85-89
Age Group (y)
Creager M, ed. Management of Peripheral Arterial
Disease. Medical, Surgical and Interventional
Aspects. 2000.
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San Diego Population Study PAD and Ethnicity
Criqui MH, et al. Circulation. 20051122703-2707.
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REACHScope of the Problem Cerebro- and
Cardiovascular Disease
63 of PAD patients had polyvascular disease N
7013
Cerebro-vascular
Coronary artery
14.2
9.5
39.4
Peripheral artery
Polyvascular disease
PAD patients with polyvascular disease had
concomitant symptomatic cerebrovascular disease
and/or CVD. REACH REduction of Atherothrombosis
for Continued Health. CVD cardiovascular
disease. Bhatt DL, et al. Presented at ACC
Scientific Session March 6-9, 2005 Orlando,
Fla.
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What is the next step in assessing the patient
for possible PAD?
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DECISION POINT

• ABI testing
• Differential diagnosis for leg pain
• Lipid/endocrine panel
• Vascular laboratory tests
• Use your keypad to vote now!

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What is the next step in assessing the patient
for possible PAD?

• ABI testing
• Differential diagnosis for leg pain
• Lipid/endocrine panel
• Vascular laboratory tests

Use your keypad to vote now!
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PAD Intermittent Claudication
Not Always Present
Patients With PAD
PARTNERS up to 90 of patients with PAD would
be missed if healthcare providers relied solely
on classic symptoms of intermittent
claudication Healthcare providers should
routinely ask about atypical symptoms In
patients with ABI 0.9.
Asymptomatic PAD 40
Symptomatic PAD 60
Typical Symptoms(Intermittent Claudication) 10
Exercise calf pain Not present at rest Relieved
within 10 minutes by rest
Atypical Symptoms50 Occlusion may develop
slowly, allowing collateral circulation to develop
AHA. Heart Disease and Stroke Statistics2008
Update. www.americanheart.org Criqui MH, et al.
Vasc Med. 1996165-71 Hirsch AT, et al. JAMA.
20012861317-1324.
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PAD Diagnostic Critical Pathway
Clinical Evaluation History and Physical

• Referral to Vascular Lab
• Assessment of location/ severity is desired
• Patients with poorly compressible vessels
• Normal ABI where PAD suspicion is high

• Vascular Lab Evaluation
• Segmental pressures
• Pulse volume recordings
• Treadmill

PAD Diagnosis
PAD Diagnosis
Adapted from American Diabetes Association.
Diabetes Care. 2003263333-3341.
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Simple Questions to Ask Your Patient Who Has
Symptoms of PAD
Do you walk?
If you do not walk, why not?
Do you have pain in either leg when you walk?
How far can you walk?
How far do you walk without stopping?
What stops you when you are walking?
Have you had any poor or non-healing leg or foot
wounds?
Olson KWP, et al. J Vasc Nurs. 20042272-77.
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PAD Physical EvaluationDifferential Diagnosis
in Patients With Intermittent Claudication

• Calf
• Venous occlusion
• Chronic compartment syndrome
• Nerve root compression
• Bakers cyst
• Hip/thigh/buttock
• Hip arthritis
• Spinal cord compression
• Foot
• Arthritis
• Buerger disease

Adapted from Schmieder FA, et al. Am J Cardiol.
2001873D-13D.
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PAD Physical Examination
Additional examination by palpation and
auscultation to detect abnormal aortic aneurysm
or bruit
Gey DC, et al. Am Fam Physician. 200469525-532.
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Physical Examination Results

• CV RRR S1 and S2 with no murmurs or gallops
• Chest clear to A/P
• Abdomen rotund, but no pulsatile masses or
  distention
• Vascular no bruits upper extremity
  pulsesnormal limits
• Lower extremity pulses reveal normal femoral
  bilaterally
• Right popliteal, DP, and PT palpable
• Left shows decreased popliteal, DP, and PT
• Musculoskeletal no evidence of foot ulceration
  or dependent rubor
• Neurologic sensory function intact in upper and
  lower extremities

DP dorsalis pedis PT posterior tibial.
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How often do you perform ABIs for patients who
have a similar clinical profile?
?
KEY QUESTION

• 0-25
• 26-50
• 51-75
• 76-100
• Use your keypad to vote now!

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How often do you perform ABIs for patients who
have a similar clinical profile?

• 0-25
• 26-50
• 51-75
• 76-100

Use your keypad to vote now!
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PAD Diagnostic Critical Pathway
Clinical Evaluation History and Physical

• Referral to Vascular Lab
• Assessment of location/ severity is desired
• Patients with poorly compressible vessels
• Normal ABI where PAD suspicion is high

• Vascular Lab Evaluation
• Segmental pressures
• Pulse volume recordings
• Treadmill

PAD Diagnosis
PAD Diagnosis
Adapted from American Diabetes Association.
Diabetes Care. 2003263333-3341.
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PARTNERS Incorporating ABI Into Primary Care
After Clinicians Participated in PARTNERS
88
Clinicians thought it feasible to incorporate ABI
into daily practice
Mohler ER, et al. Vasc Med. 20049253-260.
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ABI Indications
American Diabetes Association. Diabetes Care.
200422181-189.
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Concept of ABI
Systolic blood pressure in the leg should be
approximately the same as that in the arm
Leg Pressure
Therefore, the ratio of systolic blood pressure
in the leg versus the arm should be approximately
1 or slightly higher
1
Arm Pressure
ABI is 95 sensitive and 99 specific for
angiographically diagnosed PAD
Adapted from Weitz JI, et al. Circulation.
1996943026-3049.
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ABI Video

• Vascular Disease Foundation

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ABI Video
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ABI Workshops

• CME/CEaccredited demonstrations available
• throughout the day

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ABI Results

• Diagnostic intervention
• Evaluate vascular status ABI results
• Right 1.00
• Left 0.56

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Treatment Rationale

• The lower the ABI, the greater the risk of
  cardiovascular events
• Patients with critical leg ischemiathe most
  severe clinical manifestation of PADwho have the
  lowest ABI values have an annual mortality of 25

Hiatt WR. N Engl J Med. 20013441608-1621.
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Patient Consultation

• You tell your patient he has
• PAD
• A serious disease
• The cause of his walking problem
• A marker for the systemic disease
  atherosclerosisand he is at risk for heart
  attack or stroke

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Appropriate management of this patient should be
to
?
DECISION POINT

• Treat symptoms
• Reduce CV risk
• Treat symptoms then address CV risk reduction
• Simultaneously treat symptoms and reduce CV risk
• Use your keypad to vote now!

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Appropriate management of this patient should be
to

• Treat symptoms
• Reduce CV risk
• Treat symptoms then address CV risk reduction
• Simultaneously treat symptoms and reduce CV risk

Use your keypad to vote now!
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PAD 2-Pronged Management Strategy
Patient Management Requires BOTH Approaches
Simultaneously

• Treatment of Symptoms
• Objective
• Reduce symptoms to increase mobility, exercise
  tolerance, functional capacity
• Exercise
• Pharmacology therapy (cilostazole)
• Selective use of interventional therapy

• Risk Reduction of Ischemic Events
• Objective
• Reduce risk of events causing morbidity and
  mortality
• Control risk factors
• Antiplatelet therapy (clopidogrel)

Kempczinski RF, et al. In Rutherford RB, ed.
Vascular Surgery. 1989 Clagett GP, et al. Chest.
1995108431S-443S McDermott MM, et al. Surg
Clin North Am. 199575581-591.
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Despite its prevalence and cardiovascular risk
implications, only 25 of patients with PAD are
undergoing treatment!
PAD Undertreated

• In a recent study of 1733 patients with known
  PAD
• 33 were taking a beta blocker
• 29 were taking an ACE inhibitor
• 31 were taking a statin
• Of those with diabetes, only 46 had an A1C of
  lt7

ACE angiotensin-converting enzyme. AHA. Heart
Disease and Stroke Statistics2008 Update.
www.americanheart.org Rehring TF, et al. J Vasc
Surg. 200541816-822.
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Management PlanRisk Reduction

• Appropriate management includes
• Smoking cessation
• Blood pressure control
• Antiplatelet therapy
• Exercise program
• Order lipid/metabolic profiles
• Follow-up in 1 month

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PAD Aggressive Risk Factor ModificationSmoking
Cessation
40
35
PlaceboNicotine replacement Bupropion Bupropion
andnicotine replacement
30
25
Percentage of Patients Abstaining
20
15
10
5
0
6 Months
12 Months

• Sustained-release bupropion alone or in
  combination with nicotine patch significantly
  improved long-term smoking cessation rates
  compared with either nicotine patch alone or
  placebo
• Abstinence rates were higher (not statistically
  significant) with combination therapy than with
  bupropion alone

Jorenby DE, et al. N Engl J Med. 1999340685-691.
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Meta-Analysis PAD Aggressive Risk Factor
ModificationSupervised Exercise
AMA has published a CPT code for supervised PAD
rehabilitation (93668)2

• Greatest improvement
• Sessions lasted gt30 min
• 3 sessions/week
• Walk to near-maximal pain
• gt6-month program

CPT current procedural terminology. 1. Gardner
AW, et al. JAMA. 1995274975-980 2. Kanjwal MK,
et al. JK Practitioner. 200411225-232.
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HOPE PAD Aggressive Risk Factor
ModificationAntihypertensive Therapy

• Benefit seen independent of anti-hypertensive
  effect

Relative Risk in Ramipril Group
HOPE Study Investigators. N Engl J Med.
2000342145-153.
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Which of the following would you recommend for
the pharmacologic management of his PAD?
?
DECISION POINT

• Aspirin
• Cilostazol
• Clopidogrel
• Pentoxifylline
• Use your keypad to vote now!

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Which of the following would you recommend for
the pharmacologic management of his PAD?

• Aspirin
• Cilostazol
• Clopidogrel
• Pentoxifylline

Use your keypad to vote now!
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PAD Antiplatelet and Vasodilator Therapy
ACCP American College of Chest Physicians ASA
aspirin CAPRIE Clopidogrel Versus Aspirin in
Patients at Risk of Ischemic Events CCB
calcium channel blocker CHF chronic heart
failure GI gastrointestinal TTP thrombotic
thrombocytopenic purpura. Adapted from Gey DC,
et al. Am Fam Physician. 200469525-532.
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CAPRIEClopidogrel Versus ASA MI, Ischemic
Stroke, or Vascular Death
16
8.7 Overall RRR (P .045)
ASA Clopidogrel
5.83
12
5.32
(N 19,185)
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Cumulative Event Rate ()
Subjects had a recent MI, recent ischemic stroke,
or symptomatic PAD
4
0
0
3
6
9
12
15
18
21
24
27
30
33
36
Months of Follow-up
Median follow-up 1.91 years
ITT analysis. ITT intention to treat RRR
relative risk reduction. CAPRIE Steering
Committee. Lancet. 19963481329-1339.
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CAPRIESafety Profile

• Although the risk of myelotoxicity with
  clopidogrel appears to be low, this possibility
  should be considered when a patient receiving
  clopidogrel has fever or another sign of
  infection.
• Patients with a history of ASA intolerance were
  excluded from CAPRIE.

• Data on file, Sanofi-Synthelabo Inc. PLAVIX
  Prescribing Information. sanofi-aventis/Bristol-M
  yers Squibb Company 2007.

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Tolerability Profile
CAPRIE
ASA-intolerant patients excluded 2.5 of
patients receiving clopidogrel. Data on file,
Sanofi-Synthelabo Inc. PLAVIX Prescribing
Information. Sanofi-aventis/Bristol-Myers Squibb
Company 2007.
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Laboratory Results
Scenario 2

• Lipid panel
• Total cholesterol 276 mg/dL
• LDL-C 170 mg/dL
• HDL-C 29 mg/dL
• Triglyceride 280 mg/dL
• A1C 9.2
• FPG 204 mg/dL
• BUN 19 mg/dL creatinine 1.2 g/dL

BUN blood urea nitrogen FPG fasting plasma
glucose HDL-C high-density lipoprotein
cholesterol LDL-C low-density lipoprotein
cholesterol.
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PAD Aggressive Risk Factor ModificationDiabetes
and Hyperlipidemia
Gey DC, et al. Am Fam Physician. 200469525-532
Hiatt WR. N Engl J Med. 20013441608-1621
Norgren L, et al. J Vasc Surg. 200745S5A-S67.
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Atherosclerosis Risk in Communities Study PAD
A1C and Diabetes
A1C levels 1st tertile lt5.9 2nd tertile
6.0-7.4 3rd tertile gt7.5
Log rank P value .0006
0.06
0.05
0.04
Probability of PAD-Related Hospitalizations
0.03
0.02
0.01
0
0
2
4
6
8
10
Years of Follow-up
Selvin E, et al. Diabetes Care. 200629877-882.
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Heart Protection Study PAD Aggressive Risk
Factor ModificationLipids
0.4
0.6
0.8
1.0
1.2
1.4
Simvastatin Better
Placebo Better
. HPS Collaborative Group. MRC/BHF. Lancet.
20023607-22.
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Laboratory Results
Scenario 3

• Lipid panel
• Total cholesterol 276 mg/dL
• LDL-C 170 mg/dL
• HDL-C 29 mg/dL
• Triglyceride 280 mg/dL
• A1C 9.2
• FPG 204 mg/dL
• BUN 32 mg/dL creatinine 2.4 g/dL

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Patient Consultation

• Discuss with the patient that his renal function
  is deteriorating
• Recommend renal consultation
• Urinary albumin excretion test ordered
• Consideration may be given to renal arteriogram
• To determine presence of renal artery stenosis
  leading to diminished renal blood flow

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PAD When to Refer

• Primary care team is not confident making the
  diagnosis or lacks resources to make such a
  diagnosis
• Patient has continued symptoms despite a
  reasonable trial and adherence to best medical
  therapy
• Patient has critical limb ischemia (rest pain,
  gangrene, or ulceration)

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PAD Diagnostic Critical Pathway
Clinical Evaluation History and Physical

• Referral to Vascular Lab
• Assessment of location/ severity is desired
• Patients with poorly compressible vessels
• Normal ABI where PAD suspicion is high

• Vascular Lab Evaluation
• Segmental pressures
• Pulse volume recordings
• Treadmill

PAD Diagnosis
PAD Diagnosis
Adapted from American Diabetes Association.
Diabetes Care. 2003263333-3341.
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Vascular Laboratory Results Segmental Pressures

• Segmental pressures can help localize lesion
• Considered abnormal when there is a
• gt20 mm Hg difference between adjacent
  segments within the same leg and between the
  original segment and the corresponding segment on
  the contralateral leg

Brachial Brachial artery
Upper thigh Proximal femoral
artery
Lower thigh Distal femoral artery
Calf DP, PT, and proximal arteries
Ankle PT or DP artery
Holland T. Ostomy Wound Manage. 20024838-40,
43-46, 48-49.
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Vascular Laboratory Test Pulse Volume Recordings
Provides Segmental Waveform Analysis,
a Qualitative
Assessment of Blood Flow
UpperThigh
LowerThigh
Calf
Ankle
Normal
Normal tracingincludes initial systolic peak
with a dicrotic wave on the down slope
PAD
Abnormal tracing characterized by a rounded
systolic peak that is lower, as well as the lack
of a dicrotic wave on the downslope
Data provided by Mark Creager, MD. Holland T.
Ostomy Wound Manage. 20024838-40, 43-46, 48-49.
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Treadmill Test Function Testing to Aid Diagnosis
Clinical Evaluation History and Physical
Suspect PAD
Atypical Symptoms for PAD
ABI
Normal ABI With Typical Symptoms of Claudication

• Treadmill Function Testing
• Patients with claudication will normally display
  a drop in ankle pressure after exercise
• May also be used to assess treatment efficacy and
  evaluate overall physical function

PAD Diagnosis
Adapted from American Diabetes Association.
Diabetes Care. 2003263333-3341.
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Positioning of Dilating Balloon

• Courtesy Michael R. Jaff, DO, Director, Vascular
  Center Massachusetts General Hospital, Boston,
  Mass.

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VIDEO Postprocedure Restoration Iliac Vessel
Lumen

• Courtesy Michael R. Jaff, DO
• Director, Vascular Center
• Massachusetts General Hospital
• Boston, Massachusetts

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Postprocedure Restoration Iliac Vessel
Lumen-VIDEO
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Q A
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PCE Takeaways
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PAD in Primary Care Underdiagnosed and
Undertreated

• Prevalence is high, yet clinician awareness of
  PAD diagnosis is relatively low
• ABI can identify PAD
• PAD is a reliable warning sign that a patient is
  at high risk for life-threatening cardiovascular
  and cerebrovascular events
• Aggressive lifestyle changes and drug therapy
  can save lives

Hirsch AT, et al. JAMA. 20012861317-1324.
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Will you use ABI testing to diagnose patients at
risk for PAD?
?
KEY QUESTION

• Extremely likely
• Very likely
• Somewhat likely
• Not likely
• Use your keypad to vote now!

75
Will you use ABI testing to diagnose patients at
risk for PAD?

• Extremely likely
• Very likely
• Somewhat likely
• Not likely

Use your keypad to vote now!
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BreakClinical Application Workshops
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2008
Symposia Series 1

• Sheraton Miami Mart Hotel
• Miami, Florida
• April 5, 2008

77
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