Transcript Slide 1

Advances in the
Medical Management of
Peripheral Arterial Disease
Joshua A. Beckman, MD
Assistant Professor of Medicine
Harvard Medical School
Brigham and Women’s Hospital
Boston, Massachusetts
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 Beckman: consultant, speakers bureau:
Bristol-Myers Squibb Company, 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.
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
 PAD is caused by atherosclerotic occlusion
of the arteries to the legs
 Common, but often overlooked
 Exact prevalence is unknown
 PAD may be asymptomatic or present with
atypical symptoms
 Approximately 8-12 million Americans have PAD
 Associated with significant morbidity and mortality
resulting from MI, stroke, death
MI = myocardial infarction.
American Heart Association. Heart Disease and Stroke Statistics—2005 Update. 2005; Hiatt WR.
N Engl J Med. 2001;344:1608-1621.
PAD: Scope of the Problem
Prevalence (millions)
16
PAD affects
14
8-12 million
12
Americans,
second only to CHD*
8-12
10
13
Proportionately, for
every 4 patients seen
with CHD*, clinicians
might expect to see
approximately 3
patients with PAD
8
6
4
2
5.4
0
Stroke
PAD
CHD*
*Includes MI and angina pectoris.
CHD = coronary heart disease.
American Heart Association. Heart Disease and Stroke Statistics—2005 Update. 2005.
PAD: Prevalence Increases With Age
Patients With PAD (%)
60
Rotterdam Study (ABI <.9)
San Diego Study (PAD by noninvasive tests)
50
40
30
20
10
0
55-59
60-64
65-69
70-74
Age Group (y)
75-79
80-84
85-89
ABI = ankle-brachial index.
Creager M, ed. Management of Peripheral Arterial Disease. Medical, Surgical and Interventional
Aspects. 2000.
REACH—Scope of the Problem:
Cerebro- and Cardiovascular Disease
63% of PAD patients
had polyvascular* disease
N = 7013
Cerebrovascular
Coronary
artery
14.2%
39.4%
Polyvascular
disease
Peripheral
artery
*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.
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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PAD: Increased Risk of Mortality
Relative Risk of Death
(95% CI)
10.0
8.0
6.0
6.6
(2.9-14.9)
4.0
2.0
3.1
(1.9-4.9)
0.0
All-Cause
Mortality
Death From Coronary
Heart Disease
Cause of Death
*ABI ≤0.8.
Adapted from Criqui MH et al. N Engl J Med. 1992;326:381-386.
Patients with
large-vessel PAD*
are at ~6× the risk
of dying from
CHD compared
with patients
without PAD
HOPE
PAD: Increased Risk of Mortality
Clinical PAD
SubPAD ABI <0.6
SubPAD ABI 0.6-  0.9
No-PAD & ABI >0.9
Kaplan-Meier Rates
0.25
0.20
PAD doubled mortality rate
(17.5% vs 8.5%) after mean
follow-up of 4.5 years
0.15
0.10
0.05
P <.0001
0
0
500
1000
Days of Follow-up
HOPE = Heart Outcomes Prevention Evaluation.
Ostergren J et al. Eur Heart J. 2004;25:17-24.
1500
2000
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.
PAD: Prevalence in the
Primary Care Office Setting
NHANES1
4.3%
Age >40
San
Diego2
The prevalence
of PAD in primary
care clinics
was almost 30%
in high-risk patients
11.7%
Mean age = 66
NHANES1
14.5%
Age ≥70
Rotterdam4
19.1%
Age >55
Diehm3
19.8%
Age ≥65
PARTNERS5
29%
Age >70, or between 50-69 with history of diabetes or smoking
0%
5%
10%
15%
20%
25%
30%
35%
NHANES = National Health and Nutrition Examination Survey. PARTNERS = PAD Awareness, Risk, and Treatment
New 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.
PARTNERS
Detecting PAD With Symptoms
The authors concluded that
up to 90%*
90%
did not have
classic
intermittent
claudication
symptoms
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
*In patients with ABI ≤0.9.
Hirsch AT et al. JAMA. 2001;286:1317-1324
PAD: Symptoms
Patients With PAD
Symptomatic PAD
Asymptomatic PAD
~40%
Typical Symptoms
(Intermittent Claudication)
~10%
Exercise calf pain
Not present at rest
Relieved within 10
minutes by rest
Atypical Symptoms
~50%
Occlusion may develop
slowly, allowing collateral
circulation to develop
American Heart Association. Heart Disease and Stroke Statistics—2005 Update. 2005;
Criqui MH et al. Vasc Med. 1996;1:65-71.
PAD: Diagnostic Critical Pathway
Clinical Evaluation:
History and Physical
ABI Available
PAD
Diagnosis
Caveats for Referral to
Vascular Lab
 Assessment of location/
severity is desired
 Patients with poorly
compressible vessels
 Normal ABI where PAD
suspicion is high
ABI Not Available
Vascular Lab Evaluation
 Segmental pressures
 Pulse volume recordings
 Treadmill
PAD
Diagnosis
Adapted from American Diabetes Association. Diabetes Care. 2003:26;3333-3341.
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*
◄Lesser risk
Greater risk ►
Diabetes
4.05
Smoking
2.55
Hypertension
Patients with
diabetes are at a
4x higher risk
of developing
symptomatic PAD
versus the general
population
1.51
Total cholesterol (10 mg/dL)
1.10
0
*PAD diagnosis based on ABI <0.90.
Newman AB et al. Circulation. 1993;88:837-845.
1
2
3
4
5
Age >40 years
6
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
Additional examination by palpation and auscultation to detect
abnormal aortic aneurysm or bruit
Gey DC et al. Am Fam Physician. 2004;69:525-532.
Concept of ABI
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
Leg Pressure
÷
Arm Pressure
ABI is 95% sensitive and 99% specific for
angiographically diagnosed PAD
Adapted from Weitz JI et al. Circulation. 1996;94:3026-3049.
≈1
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
=
Right Leg ABI
Left Leg ABI
Higher right ankle
pressure
(DP or PT pulse)
Higher left ankle
pressure
(DP or PT pulse)
Higher arm pressure
(either arm)
=
Higher arm pressure
(either arm)
ABI Interpretation
≤0.90 is diagnostic of PAD
Hiatt WR. N Engl J Med. 2001;344:1608-1621.
ABI Workshops
 Demonstrations available throughout the day
PARTNERS
Incorporating ABI Into Primary Care
After Clinicians Participated in PARTNERS:
88%
358%
300%
Weekly Increase in
ABI Use in Office
Monthly Increase in
ABI Use in Office
Mohler, ER et al. Vasc Med. 2004; 9:253-260.
Clinicians thought it
feasible to
incorporate ABI into
daily practice
PAD: Diagnostic Critical Pathway
Clinical Evaluation:
History and Physical
ABI Available
PAD
Diagnosis
Caveats for Referral to
Vascular Lab
 Assessment of location/
severity is desired
 Patients with poorly
compressible vessels
 Normal ABI where PAD
suspicion is high
ABI Not Available
Vascular Lab Evaluation
 Segmental pressures
 Pulse volume recordings
 Treadmill
PAD
Diagnosis
Adapted from American Diabetes Association. Diabetes Care. 2003;26:3333-3341.
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
Holland T. Ostomy Wound Manage. 2002;48:38-40,43-46,48-49.
Vascular Laboratory Test:
Pulse Volume Recordings
Provides Segmental Waveform Analysis,
A Qualitative Assessment of Blood Flow
Upper
Thigh
Lower
Thigh
Calf
Ankle
Normal tracing
Normal
includes initial
systolic peak with
a dicrotic wave on
the down slope
Abnormal tracing
PAD
Data provided by Mark Creager, MD.
Holland T. Ostomy Wound Manage. 2002;48:38-40,43-46,48-49.
characterized by a
rounded systolic peak
that is lower, as well as
the lack of a dicrotic
wave on the downslope
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. 2003;26:3333-3341.
Key Question
The goals of therapy for PAD are:
1. Relieve exertional symptoms
2. Improve walking capability
3. Improve quality of life
4. Relieve ischemic pain at rest
5. Heal ischemic ulceration
6. Prevent limb loss
7. All of the above
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PAD: Treatment Goals
 For patients with claudication
 Relieve
exertional symptoms
 Improve walking capability
 Improve quality of life
 For patients with critical leg ischemia
 Same as above, and
Relieve ischemic pain at rest
Heal ischemic ulceration
Prevent limb loss
Hiatt WR. N Engl J Med. 2001;344:1608-1621.
PAD: Aggressive Risk Factor
Modification Essential—1
Smoking
Cessation
Goal: Abstinence
↓ Severity of claudication
(probably)
Slows progression to critical leg
ischemia
↓ MI risk, vascular deaths
Exercise
↑ Peak walking time
Goal: As
frequently and as
long as possible
↑ Peak oxygen consumption
↑ Pain-free walking time
↑ Quality of life
↑ Routine daily activities
Pharmacotherapy
(NRT, nortriptyline,
clonidine, bupropion)
+ counseling
Therapeutic exercise
training
NRT = nicotine replacement therapy.
Gey DC et al. Am Fam Physician. 2004;69:525-532; Hiatt WR. N Engl J Med. 2001;344:1608-1621;
Stewart KJ et al. N Engl J Med. 2002;347:1941-1951.
Percentage of Patients
Abstaining
PAD: Aggressive Risk Factor Modification
Essential—Smoking Cessation
40
35
Placebo
Nicotine replacement
Buproprion
Bupropion and
nicotine replacement
30
25
20
15
10
5
0
6 months
12 months
Jorenby DE et al. N Engl J Med. 1999;340:685-691.
Meta-Analysis
Supervised Exercise Essential to Improve
Intermittent Claudication Symptoms
Percentage Increase
179%
122%
Distance to Maximal
Claudication Pain
Distance to Onset of
Claudication Pain
At 6 months
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
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.
PAD: Aggressive Risk Factor Modification
Essential—2
Treat Hyperlipidemia
Goal:
LDL <100 mg/dL
Treat Hypertension
Goal:
<140/90 mm Hg
<130/80 mm Hg (diabetes
or renal insufficiency)
Control Diabetes
Goal:
A1C <7% or as close to
normal (<6%) as
possible
↓ Serum cholesterol
↑ Endothelial function
↓ Disease progression
Modifies other atherosclerotic risks
Statins
Niacins
Data support aggressive treatment;
impact on PAD outcomes unclear
ACE inhibitors
Beta-blockers
can be used
↓ 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
Type of major vascular event
Coronary events
Nonfatal MI
Coronary death
Subtotal: major coronary
events
Strokes
Nonfatal strokes
Fatal strokes
SimvastatinAllocated
(10269)
PlaceboAllocated
(10267)
357 (3.5%)
587 (5.7%)
574 (5.6%)
707 (6.9%)
898 (8.7%)
1212 (11.8%)
366 (3.6%)
96 (0.9%)
499 (4.9%)
119 (1.2%)
Subtotal: any strokes
444 (4.3%)
585 (5.7%)
Revascularization
Coronary
Noncoronary
Subtotal: any revascularization
513 (5.0%)
450 (4.4%)
939 (9.1%)
725 (7.1%)
532 (5.2%)
1205 (11.7%)
2033 (19.8%)
2585 (25.2%)
Any Major Vascular Event
0.4
Event Rate Ratio (95% CI)
0.73 (0.67-0.79)
P <.0001
0.75 (0.66-0.86)
P <.0001
0.76 (0.70-0.83)
P <.0001
0.76 (0.72-0.81)
P <.0001
0.6
0.8
Simvastatin Better
HPS = Heart Protection Study.
HPS Collaborative Group. MRC/BHF. Lancet. 2002;360:1329-1239.
1.0
1.2
1.4
Placebo Better
HOPE
PAD: Aggressive Risk Factor Modification
Essential—Antihypertensive Therapy
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
0.8
1.0
1.2
Relative Risk in Ramipril Group
HOPE Study Investigators. N Engl J Med. 2000;342:145-153.
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.
CAPRIE
Clopidogrel Versus ASA: MI,
Ischemic Stroke, or Vascular Death
Cumulative Event Rate (%)
16
Clopidogrel
ASA
12
8.7%
Overall RRR
(P = .045)*
5.83%
5.32%
(N = 19,185)
8
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: RRR = relative risk reduction.
CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.
CAPRIE
Safety Profile
% 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
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.
PLAVIX Prescribing Information.
Data on file, Sanofi-Synthelabo Inc.
CAPRIE
Tolerability Profile*
% Patients
Abdominal pain
Purpura (bruising)
Dyspepsia
Diarrhea
Rash
Pruritis
Discontinuation due to adverse GI events
Gastritis
*ASA-intolerant patients excluded.
PLAVIX Prescribing Information.
Data on file, Sanofi-Synthelabo Inc.
Clopidogrel
(75 mg/d)
5.6
5.3
5.2
4.5
4.2
3.3
3.2
0.8
ASA*
(325 mg/d)
7.1
3.7
6.1
3.4
3.5
1.6
4.0
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 examination
 Height:
5'9″
 Weight: 190 lb
 BMI: 28.1 kg/m2
 Waist circumference: 40″
 BP: 168/110 mm Hg
 Pulse: 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 panel
 Total
cholesterol: 346 mg/dL
 LDL: 170 mg/dL
 HDL: 29 mg/dL
 Triglyceride: 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 = 1.00
Left = 0.56
 Appropriate management includes:
 Control BP
 Manage dyslipidemia and diabetes
 Initiate antiplatelet therapy
 Smoking cessation
 Exercise program
 Follow-up in 1 month
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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