Advances in theMedical Management of
Peripheral Arterial DiseaseWalter A. Tan, MD, MS
Associate Professor of Medicine
Clinical Associate Professor of Surgery
Director of Stroke Interventions
The Brody School of Medicine
East Carolina University
Greenville, North Carolina
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 Tan: speakers bureau, honoraria: Bristol-Myers Squibb Company, sanofi-aventis Group.
Experimental application of devices and off-label use of drugs may be discussed in this presentation.
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.
Key Question
How common is PAD?
1. 1-4 million Americans
2. 4-8 million Americans
3. 8-12 million Americans
4. 12-16 million Americans
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PAD: Scope of the Problem
Stroke PAD CHD*0
2
4
6
8
10
12
14
Pre
vale
nce
(m
illi
on
s)
16
5.4
138-12
PAD affects 8-12 million Americans,
second only to CHD*
Proportionately, for every 4 patients seen with CHD*, clinicians might expect to see
approximately 3 patients with PAD
*Includes MI and angina pectoris.CHD = coronary heart disease. American Heart Association. Heart Disease and Stroke Statistics—2005 Update. 2005.
REACH—Scope of the Problem:Cerebro- and Cardiovascular Disease
*PAD patients with polyvascular disease had concomitant symptomatic cerebrovascular disease and/or CVD. REACH = REduction of Atherothrombosis for Continued Health.
Bhatt DL et al. American College of Cardiology Scientific Session. March 8, 2005.
Coronary artery
Peripheral artery
39.4%
14.2%
9.5%
Polyvascular disease
63% of PAD patients had polyvascular* disease
N = 7013
Cerebro-vascular
Atherosclerosis: Rust in Old Pipes
PAD: Prevalence Increases With Age
ABI = ankle-brachial index.Creager M, ed. Management of Peripheral Arterial Disease. Medical, Surgical and Interventional Aspects. 2000.
Rotterdam Study (ABI <.9) San Diego Study (PAD by noninvasive tests)
Age Group (y)
Pat
ien
ts W
ith
PA
D (
%)
0
10
20
30
40
50
60
55-59 60-64 65-69 70-74 75-79 80-84 85-89
Key Question
PAD increases the risk of CHD death by approximately:
1. 1×-2×
2. 3×-4×
3. 5×-6×
4. 6×-7×
5. 7×-8×
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Cause of Death
PAD: Increased Risk of Mortality
0.0
2.0
4.0
6.0
8.0
10.0
All-Cause Mortality
Death From Coronary Heart Disease
Rel
ativ
e R
isk
of
Dea
th
(95%
CI)
3.1(1.9-4.9)
6.6(2.9-14.9)
Patients with large-vessel PAD*
are at ~6× the risk of dying from
CHD comparedwith patients without PAD
*ABI ≤0.8.Adapted from Criqui MH et al. N Engl J Med. 1992;326:381-386.
HOPEPAD: Increased Risk of Mortality
HOPE = Heart Outcomes Prevention Evaluation.Ostergren J et al. Eur Heart J. 2004;25:17-24.
PAD doubled mortality rate (17.5% vs 8.5%) after mean follow-up of 4.5 years
0.25
0.20
0.15
0.10
0.05
0
0 500 1000 1500 2000
P <.0001Kap
lan
-Mei
er R
ates
Days of Follow-up
Clinical PADSubPAD ABI <0.6SubPAD ABI 0.6- 0.9No-PAD & ABI >0.9
CAD: Prevalence
Age (y) No PAD (%)Asymptomatic
PAD (%)Symptomatic
PAD (%)
40-49 5.9 15.0 20.0
50-59 15.7 33.3 34.8
60-69 28.7 46.3 50.9
≥70 34.1 52.5 52.5
Total 19.8 43.3 43.5
Hooi JD et al. Scand J Prim Health Care. 1998;16:177-182.
PAD in Primary Care: Underdiagnosed
Prevalence is high, yet clinician awareness of PAD diagnosis is relatively low
Simple ABI measurement identifies many patients with previously unrecognized PAD
Atherosclerosis risk factors are prevalent in patients with PAD Received less intensive treatment for lipid disorders
and hypertension Prescribed antiplatelet therapy less frequently
than patients with CVD
Hirsch AT et al. JAMA. 2001;286:1317-1324.
NHANES = National Health and Nutrition Examination Survey. PARTNERS = PAD Awareness, Risk, and TreatmentNew Resources for Survival program. 1. Selvin E, Erlinger TP. NHANES. Circulation. 2004;110:738-743; 2. Criqui MH et al. Circulation. 1985;71:510-515;3. Meijer WT et al. Arterioscler Thromb Vasc Biol. 1998;18:185-192; 4. Diehm C et al. Atherosclerosis. 2004;172:95-105; 5. Hirsch AT et al. JAMA. 2001;286:1317-1324.
PAD: Prevalence in the Primary Care Office Setting
29%
19.8%
19.1%
14.5%
11.7%
4.3%
0% 5% 10% 15% 20% 25% 30% 35%
The prevalence of PAD in primary
care clinics was almost
in high-risk patients
PARTNERS5
Age >70, or between 50-69 with history of diabetes or smoking
San Diego2 Mean age = 66
Diehm3 Age ≥65
Rotterdam4 Age >55
NHANES1 Age ≥70
NHANES1
Age >40
30%
The authors concluded that up to 90%*
of patients with PAD would be missed if healthcare
providers relied solely on the classic symptoms of intermittent claudication
Healthcare providers should also routinely inquire about
atypical symptoms
90% did not have
classic intermittent claudication symptoms
PARTNERS
Detecting PAD With Symptoms
*In patients with ABI ≤0.9.Hirsch AT et al. JAMA. 2001;286:1317-1324
PAD: Symptoms
American Heart Association. Heart Disease and Stroke Statistics—2005 Update. 2005;Criqui MH et al. Vasc Med. 1996;1:65-71.
Typical Symptoms(Intermittent Claudication)
~10%Exercise calf painNot present at restRelieved within 10
minutes by rest
Atypical Symptoms~50%
Occlusion may develop slowly, allowing collateral
circulation to develop
Asymptomatic PAD~40%
Patients With PAD
Symptomatic PAD
Adapted from American Diabetes Association. Diabetes Care. 2003:26;3333-3341.
PAD: Diagnostic Critical Pathway
PAD Diagnosis
Vascular Lab Evaluation Segmental pressures Pulse volume recordings Treadmill
ABI Not AvailableABI Available
PAD Diagnosis
Referral to Vascular Lab Assessment of location/
severity is desired Patients with poorly
compressible vessels Normal ABI where PAD
suspicion is high
Clinical Evaluation:History and Physical
Key Question
The most common risk factor for PAD is:
1. Diabetes
2. Smoking
3. Hypertension
4. Total cholesterol level
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PAD: Common Risk Factors*
*PAD diagnosis based on ABI <0.90.Newman AB et al. Circulation. 1993;88:837-845.
◄Lesser risk
0 1 2 3 4 5 6
1.10
1.51
2.55
Total cholesterol (10 mg/dL)
Hypertension
Diabetes
Smoking
Greater risk ►
Patients with diabetes are at a 4x higher risk of developing
symptomatic PAD versus the general
population
4.05
Age >40 years
PAD: Physical Examination
Perform With Patient’s Pants/Shoes Off
Examine Limb And Compare With the Opposite Limb
Absent/diminished femoral or pedal pulses—especially after exercising the limb
Arterial bruits
Hair loss
Poor nail growth (brittle nails)
Dry, scaly, atrophic skin
Dependent rubor
Pallor with leg elevation after 1 minute at 60º (normal color should return in 10-15 seconds; >40 seconds indicates severe ischemia)
Ischemic tissue ulceration (punched-out, painful, little bleeding), gangrene
Gey DC et al. Am Fam Physician. 2004;69:525-532.
Additional examination by palpation and auscultation to detect abnormal aortic aneurysm or bruit
Concept of ABI
Adapted from Weitz JI et al. Circulation. 1996;94:3026-3049.
÷ ≈ 1
ABI is 95% sensitive and 99% specific for angiographically diagnosed PAD
Systolic BP in the leg should be approximately the same as that in the arm
Therefore, the ratio of systolic BP in the leg versus the arm should be approximately 1 or slightly higher
Arm Pressure
Leg Pressure
Measuring ABI
Gather equipment needed Position patient Measure the brachial BP Position the cuff above the ankle Measure pressure in the DP artery Measure pressure in the PT artery Repeat the process in opposite leg
DP = dorsalis pedis; PT = posterior tibial.American Diabetes Association. Diabetes Care. 2003;26:3333-3341; Dormandy JA et al. J Vasc Surg. 2000;31:S1-S296.
Calculating ABI
Higher right ankle pressure
(DP or PT pulse)
Higher arm pressure (either arm)
=
Right Leg ABI Left Leg ABI
Higher left ankle pressure
(DP or PT pulse)
Higher arm pressure (either arm)
=
ABI Interpretation≤0.90 is diagnostic of PAD
Hiatt WR. N Engl J Med. 2001;344:1608-1621.
ABI and Mortality
Adapted from: Resnick HE. Circulation. 2004;109:733-739.
Baseline ABI
0
10
20
30
40
50
60
70
Per
cen
t (%
)
All-cause mortality
CVD mortality
<0.60
(n=25)
0.60 - <0.70
(n=21)
0.70 - <0.80
(n=40)
0.80 - <0.90
(n=130)
0.90 - <1.0
(n=195) 1.0 - < 1.1
(n=980)1.40 -
<.1.5
(n=136) 1.5
(n=89) Incom-
pressible(n=179)
/ /
ABI Workshops
Demonstrations available throughout the day
PARTNERS Incorporating ABI Into Primary Care
Weekly Increase in ABI Use in Office
358%
Monthly Increase inABI Use in Office
300%
88%
Mohler, ER et al. Vasc Med. 2004; 9:253-260.
Clinicians thought it feasible to
incorporate ABI into daily practice
Clinicians thought it feasible to
incorporate ABI into daily practice
After Clinicians Participated in PARTNERS:
Adapted from American Diabetes Association. Diabetes Care. 2003;26:3333-3341.
PAD: Diagnostic Critical Pathway
PAD Diagnosis
Vascular Lab Evaluation Segmental pressures Pulse volume recordings Treadmill
ABI Not AvailableABI Available
PAD Diagnosis
Referral to Vascular Lab Assessment of location/
severity is desired Patients with poorly
compressible vessels Normal ABI where PAD
suspicion is high
Clinical Evaluation:History and Physical
Holland T. Ostomy Wound Manage. 2002;48:38-49.
Vascular Laboratory Results: Segmental Pressures
• Segmental pressures can help localize lesion
• Considered abnormal when there is a
>20 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
Provides Segmental Waveform Analysis, A Qualitative Assessment of Blood Flow
Data provided by Mark Creager, MD.Holland T. Ostomy Wound Manage. 2002;48:38-40,43-46,48-49.
Normal
PAD
Normal tracingincludes initial systolic peak with a dicrotic wave on the down slope
Vascular Laboratory Test: Pulse Volume Recordings
UpperThigh
LowerThigh Calf Ankle
Abnormal tracing characterized by a rounded systolic peak that is lower, as well as the lack of a dicrotic wave on the downslope
Duplex ultrasound for lesion physiology
Adapted from American Diabetes Association. Diabetes Care. 2003;26:3333-3341.
Atypical Symptoms
for PAD
PAD Diagnosis
Treadmill Test: Function Testing to Aid Diagnosis
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
Normal ABI with typical symptoms of claudication
ABI
Suspect PAD
Clinical Evaluation: History and Physical
Noninvasive Imaging Options
Key Question
The goals of therapy for PAD are:1. Relieve exertional symptoms2. Improve walking capability3. Improve quality of life4. Relieve ischemic pain at rest5. Heal ischemic ulceration6. Prevent limb loss7. All of the above
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PAD: Treatment Goals
For patients with claudicationRelieve exertional symptoms Improve walking capability Improve quality of life
For patients with critical leg ischemiaSame as above, and
Relieve ischemic pain at restHeal ischemic ulcerationPrevent limb loss
Hiatt WR. N Engl J Med. 2001;344:1608-1621.
PAD: Aggressive Risk Factor Modification Essential—Smoking Cessation
Jorenby DE et al. N Engl J Med. 1999;340:685-691.
PlaceboNicotine replacementBuproprionBupropion andnicotine replacement
40
35
30
25
20
15
10
5
0Per
cen
tag
e o
f P
atie
nts
A
bst
ain
ing
6 months 12 months
CPT = current procedural terminology.1. Gardner AW et al. JAMA. 1995;274:975-980; 2. Kanjwal MK et al. JK–Practitioner. 2004;11:225-232.
Distance to Maximal Claudication Pain
Distance to Onset of Claudication Pain
At 6 months
122% 179%
Per
cen
tag
e In
crea
seMeta-Analysis Supervised Exercise Essential to Improve Intermittent Claudication Symptoms
AMA has published a CPT code for supervised PAD rehabilitation (93668)2
Greatest improvement: • Sessions lasted >30 min• 3 sessions/wk• Walk to near-maximal pain• >6-month program
PAD: Aggressive Risk Factor Modification Essential—2
Treat Hyperlipidemia
Goal:
LDL <100 mg/dL
↓ Serum cholesterol↑ Endothelial function↓ Disease progressionModifies other atherosclerotic risks
StatinsNiacins
Treat Hypertension
Goal:
<140/90 mm Hg
<130/80 mm Hg (diabetes or renal insufficiency)
Data support aggressive treatment; impact on PAD outcomes unclear
ACE inhibitorsBeta-blockerscan be used
Control Diabetes
Goal:
A1C <7% or as close to normal (<6%) as possible
↓ CVD and MI rates; trend for PAD outcomes ↓ Limb infection, amputation↓ Microvascular complication risk
Diet, exercise, pharmacotherapy
A1C = glycosylated hemoglobin.Gey DC et al. Am Fam Physician. 2004;69:525-532; Hiatt WR. N Engl J Med. 2001;344:1608-1621; Norgren L et al. J Vasc Surg. 2007;45:S5A-S67.
HPS PAD: Aggressive Risk Factor Modification Essential—Lipids
HPS = Heart Protection Study.HPS Collaborative Group. MRC/BHF. Lancet. 2002;360:7-22.
Type of major vascular event
Simvastatin-Allocated(10269)
Placebo-Allocated(10267)
Event Rate Ratio (95% CI)
Coronary events
0.73 (0.67-0.79)P <.0001
0.75 (0.66-0.86)P <.0001
0.76 (0.70-0.83)P <.00010.76 (0.72-0.81)P <.0001
Nonfatal MI 357 (3.5%) 574 (5.6%)
Coronary death 587 (5.7%) 707 (6.9%)Subtotal: major coronary events 898 (8.7%) 1212 (11.8%)
Strokes
Nonfatal strokes 366 (3.6%) 499 (4.9%)
Fatal strokes 96 (0.9%) 119 (1.2%)
Subtotal: any strokes 444 (4.3%) 585 (5.7%)
Revascularization
Coronary 513 (5.0%) 725 (7.1%)
Noncoronary 450 (4.4%) 532 (5.2%)
Subtotal: any revascularization 939 (9.1%) 1205 (11.7%)
Any Major Vascular Event 2033 (19.8%) 2585 (25.2%)
0.4 0.6 0.8 1.0 1.2 1.4Simvastatin Better Placebo Better
HOPE PAD: Aggressive Risk Factor Modification Essential—Antihypertensive Therapy
HOPE Study Investigators. N Engl J Med. 2000;342:145-153.
No. of Patients
Incidence of Composite Outcome in
Placebo Group
Overall 9297 17.8
PAD 4046 22.0
No PAD 5251 14.3
0.6
Relative Risk in Ramipril Group
0.8 1.0 1.2
PAD: Antiplatelet and Vasodilator Therapy
ASA 81-325 mg/d PO Recommended by ACCP; not FDA-approved
Clopidogrel 75 mg/d PO
Fewer side effects than ASA in CAPRIE trial; significantly less TTP risk than ticlopidine
Pentoxifylline 1.2 g/d PO
Some effect on walking ability; insufficient data to support widespread use
Cilostazol 100 mg BID PO
Correct dosage critical; avoid in patients with CHF; reduce dose in patients taking CCBs; GI side effects
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. 2004;69:525-532.
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 analysis: RRR = relative risk reduction.CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.
CAPRIEClopidogrel Versus ASA: MI, Ischemic Stroke, or Vascular Death
CAPRIE
Safety Profile
•Patients with a history of ASA intolerance were excluded from CAPRIE. PLAVIX Prescribing Information. Data on file, Sanofi-Synthelabo Inc.
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
Clopidogrel
(n = 9599)
ASA* (n =
9586)
GI hemorrhage 2.0 2.7
Hospitalization due to GI hemorrhage
0.7 1.1
GI ulcers 0.7 1.2
Intracranial hemorrhage 0.4 0.5
Severe neutropenia 0.04 0.02
Tolerability Profile*
*ASA-intolerant patients excluded.PLAVIX Prescribing Information. Data on file, Sanofi-Synthelabo Inc.
CAPRIE
% Patients
Clopidogrel (75 mg/d)
ASA*
(325 mg/d)
Abdominal pain 5.6 7.1
Purpura (bruising) 5.3 3.7
Dyspepsia 5.2 6.1
Diarrhea 4.5 3.4
Rash 4.2 3.5
Pruritus 3.3 1.6
Discontinuation due to adverse GI events 3.2 4.0
Gastritis 0.8 1.3
PAD: When to Refer
Primary care team is not confident making the diagnosis or lacks resources required 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)
Case Study
Patient Case Study
58-year-old Latino male History of diabetes and hypertension
Treated episodically at local clinic No current medications
Has taken antihypertensive and oral hypoglycemic agents in the past
Patient Case Study
Physical examinationHeight: 5'9″Weight: 190 lbBMI: 28.1 kg/m2
Waist circumference: 40″BP: 168/110 mm HgPulse: 72 bpm
BMI = body mass index.
Presenting Symptoms
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 labs and diagnostic studies
Admits that he has never been on medication for more than 3 months at a time Has no health benefits and works as a construction worker
Does not drink alcohol but smokes 1 pack/day x 30 years Complains of fatigue and inability to maintain his current
productivity at the work site
Laboratory Results
Lipid panelTotal cholesterol: 346 mg/dLLDL: 170 mg/dLHDL: 29 mg/dLTriglyceride: 280 mg/dL
A1C: 9.2% BUN and creatinine: 19/1.4 mg/dL
BUN = blood urea nitrogen; HDL = high-density lipoprotein; LDL = low-density lipoprotein.
Physical Examination
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 pulses—normal 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
Decision Point
What is this patient’s risk category?
1. High
2. Moderately high
3. Moderate
4. Either moderate or moderately high
5. Low
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Therapeutic Considerations
Diagnostic intervention Evaluate vascular status ABI results
Right = 1.00Left = 0.56
Appropriate management includes: Control BP Manage dyslipidemia and diabetes Initiate antiplatelet therapy Smoking cessation Exercise program Follow-up in 1 month
Q & A
PCE Takeaways
PCE: PAD Takeaways
PAD is underrecognized and undertreated ABI can identify PAD Aggressive lifestyle changes and drug therapy
can save lives
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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