1. Advances in the Medical Management of Peripheral Arterial Disease
Warner P. Bundens, MD, MS
Associate Clinical Professor of Surgery
Associate Clinical Professor of Family and Preventive Medicine
School of Medicine
University of California, San Diego
La Jolla, California

2. ? Key Question How many of your patients with CV risk do
you test for peripheral arterial disease?
0%-24%
25%-50%
51%-75%
76%-100%
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3. Faculty Disclosure
Dr Bundens: grants/research support: sanofi-aventis Group.

4. 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.

5. Peripheral Arterial Disease: What Is It?
PAD
PAOD
PAOD = peripheral arterial obstructive disease.

6. What Is It?
Lesions
Obstructed Lumen
Plaque

7. Who Gets It? PAD: Risk Factors Age Uncommon: <50 years old
10% overall
20% with history of smoking or diabetes
>70 years old
20%
NOTE – Lots of people have it.

8. Who Gets It? PAD: Risk Factors Age Diabetes 4× Smoking 3.5×
Past or present
Hypertension 2×
Hyperlipidemia 0.1×

9. How Do You Diagnose It?
PAD Symptoms
May be asymptomatic
Claudication

10. A Reproducible and Consistent Symptom
Claudication
A Reproducible and
Consistent Symptom

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

12. Claudication

13. Claudication
Muscular pain brought on by activity (walking) that is relieved by stopping that activity
Does not occur at rest
Is not brought on by standing

14. 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

15. How Do You Diagnose It? PAD Symptoms May be asymptomatic Claudication
Ischemic rest pain

16. Ischemic Rest Pain Distal foot Worse at night
Decreased by lowering foot

17. How Do You Diagnose It? PAD Symptoms May be asymptomatic Claudication
Ischemic rest pain
Tissue loss, nonhealing lesions, gangrene

18. Arterial Ulcer/Gangrene

19. Nocturnal Leg/Foot Cramps
Not Arterial
Nocturnal Leg/Foot Cramps

20. PAD: Physical Findings
Pulses
Pallor
Dependent rubor
Thick nails
Hairlessness
Tissue loss/ulcer/gangrene

21. PAD: Physical Findings
Poor Sensitivity and Specificity
for Mild-to-Moderate PAD

22. PAD: An Objective Test
Flow vs Pressure

23. Ohm’s Law Electrical: E = I·R Voltage Drop = Current × Resistance
Fluids: P = F·R
Pressure Drop = Flow × Resistance

24. Ohm’s Law

25. Office Measurement of the Ankle-Brachial Index (ABI)
Supine
Patient
Right arm pressure
Left arm pressure
Office Measurement of the ABI
The ankle–brachial index (or ABI) is the ratio of systolic blood pressure in the ankle to systolic blood pressure in the arm. This measurement tool permits clinicians to both objectively detect PAD and assess its severity. The ABI is a simple, inexpensive, and reliable indicator of limb perfusion, and can be done in the office. It requires a 5-7 MHz Doppler ultrasound probe rather than a stethoscope to ensure accuracy and facilitate measurement of the ankle blood pressure.
ABI measurements should be performed during the examination of any patient who is considered to be at risk for PAD or who complains of exertional leg pain. The measurement is made by using the Doppler device to identify appropriate arteries. Using a standard BP cuff, the systolic pressure is taken in both ankles at the dorsalis pedis (DP) and posterior tibial (PT) arteries and at the brachial arteries in both arms.
Pressure:
Posterior tibial
Anterior tibial
Pressure:
Posterior tibial Anterior tibial

26. Ankle Pressure
Patient Must Be Supine
Posterior Tibial Anterior Tibial

27. Ankle Systolic Pressure Brachial Artery Systolic Pressure
The ABI
Ankle Systolic Pressure
Brachial Artery Systolic Pressure
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
Understanding the ABI
The ABI is considered the “gold standard” for determining the presence of PAD and assessing its severity. It is determined by dividing the higher of the two systolic blood pressures at each ankle by the higher of the two systolic blood pressures in each arm. The ankle pressures may be obtained over either the dorsalis pedis or the posterior tibial artery.
The ABI boasts a 95% sensitivity and 99% specificity for diagnosing PAD. Indeed, the Doppler ankle systolic pressure has been shown to correlate closely with direct intraarterial recordings. For this reason, the ABI is considered the most useful noninvasive test available for epidemiologic studies of PAD. It should be remembered, however, that the ABI assesses PAD, not intermittent claudication.

28. The ABI Right Arm 150 mm Hg Right AT 68 Right PT 75 Left Arm 143
Left AT
Left PT
Right ABI = 75/150 = 0.50
Left ABI = 120/150 = 0.80
AT = anterior tibial; PT = posterior tibial.

29. What Do the Numbers Mean?
ABI
Typical values
Normal =
Claudication =
Rest pain = <0.4
Tissue loss = <0.3

30. ? ABI <0.90 95% Sensitive and 99% Specific for PAD
TASC Working Group. J Vasc Surg. 2000;31(1 suppl):S1-S296.

31. ABI: Occasional “Gray” Areas
Most of these people have PAD
ABI >1.0
Most of these people do not have PAD

32. ABI Workshops
Demonstrations available throughout the day

33. Further Noninvasive Testing
Segmental pressures
Doppler waveforms
Exercise test

34. Lower Extremity Arterial Exam
Further Testing
Lower Extremity Arterial Exam

35. Relative 5-Year Mortality Rates
PAD Is a Bad Disease
Relative 5-Year Mortality Rates
*American Cancer Society. Cancer Facts and Figures, 2000.
Criqui MH et al. N Engl J Med. 1992;326:

36. WHY ?

37. ? Key Question Without intervention, what percentage of
PAD patients will have an MI or stroke in
the next 5 years?
10%
25%
50%
75%
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MI = myocardial infarction.

38. Clinical Outcomes in Patients With PAD
PAD Patient
Asymptomatic
50%
Intermittent claudication
40%
Critical leg ischemia
10%
Cardiovascular
morbidity/mortality
PAD outcomes
(5-year outcomes)
Clinical Outcomes in Patients with PAD
Although PAD follows the same course in patients with vascular disease as it does in the general population, the percentage of affected individuals is higher. As noted here, half of all affected patients >55 years old are asymptomatic, whereas 40% experience intermittent claudication and 10% have critical leg ischemia. Five years after diagnosis, nearly three quarters of all claudicants remain symptomatically stable. A much smaller percentage (16%) experience worsening symptoms, and in 11% the situation deteriorates to the point where bypass surgery or amputation is needed.
While PAD itself is not generally life-threatening, there is a high associated morbidity and mortality from CVD and cerebrovascular disease. Five years after diagnosis, 20% of affected persons will have had a nonfatal stroke or MI and another 20% to 30% will have died from such events.
Stable claudication 73%
Worsening claudication 16%
Leg bypass surgery 7%
Major amputation 4%
Nonfatal events
(MI/stroke)
20%
Mortality 30%
Adapted from Weitz Jl. Circulation. 1996;94:

39. PAD and All-Cause Mortality*
1.00
Normal subjects Asymptomatic LV-PAD† Symptomatic LV-PAD† Severe symptomatic LV-PAD†
0.75
Survival
0.50
0.25
0.00 2 4 6 8 10 12
Year
*Kaplan-Meier survival curves based on mortality from all causes.
†Large-vessel PAD
Adapted from Criqui MH et al. N Engl J Med. 1992;326:

40. Diagnosis Treatment 2 Problems Cardiovascular Leg Symptoms Risk
Claudication
Rest Pain
Tissue Loss

41. Cardiovascular Risk Treatment 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
Hirsch A et al. J Am Coll Cardiol, 2006;47:

42. Antiplatelet Medications
Aspirin

43. ? Key Question What is the proper daily dose of aspirin
for cardiovascular risk reduction?
75 mg
81 mg
300 mg
325 mg
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44. Antiplatelet Medications
Aspirin 81 mg/d

45. Aspirin Dosage Antiplatelet Medications Aspirin Dose No. Trials OR (%)mg mg mg
<75 mg
Any aspirin
0.5
1.0
1.5
2.0
Antiplatelet Better
Antiplatelet Worse
OR = odds ratio.
Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86.

46. Aspirin Dosage: Risk of Major Bleeding
Antiplatelet Medications
Aspirin Dosage: Risk of Major Bleeding
Clopidogrel
+ Aspirin
Placebo
+ Aspirin
Aspirin Dose
<100 mg % %
mg % %
>200 mg % %
CURE Trial. Circulation. 2003;108:

47. Antiplatelet Medications
Aspirin
81 mg
Clopidogrel
75 mg

48. CAPRIE Clopidogrel vs ASA: MI, Ischemic Stroke, or Vascular Death16
8.7%
Overall RRR
(P = .045)*
Clopidogrel
ASA
5.83% 12
5.32%
(N = 19,185) 8
Cumulative Event Rate (%)
Subjects had a recent MI, recent ischemic stroke, or symptomatic PAD 4
The primary outcome analysis in CAPRIE was based on the composite end point of MI, ischemic stroke, or vascular death among all randomized patients (intent-to-treat analysis). Only the first occurrence of these outcomes was counted. The total number of patients randomized was 9,599 for clopidogrel bisulfate and 9,586 for aspirin.[1]
Results from the CAPRIE trial demonstrated that clopidogrel had a lower event rate per year compared with aspirin, 5.32% vs 5.83%, respectively, which resulted in an overall risk reduction of 8.7%[1] (P=0.045)[2] vs aspirin. An on-treatment analysis of the primary event cluster showed a relative risk reduction of 9.4%[1] (P=0.046).[3]
Although the statistical significance favoring clopidogrel bisulfate (Plavix®) over aspirin was marginal (P=0.045, based on overall incidence of primary outcome events: 9.78% for clopidogrel vs 10.64% for aspirin), and represents the result of a single trial that has not been replicated, the comparator drug, aspirin, is itself effective (vs placebo) in reducing cardiovascular events in patients with recent MI or stroke. Thus, the difference between clopidogrel and placebo, although not measured directly, is substantial.[2]
The cumulative risk curves separated early and continued to diverge during the 3-year follow-up period.[1]
CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:
Plavix® (clopidogrel bisulfate) Prescribing Information. Sanofi-Synthelabo Inc.
Data on file, Sanofi-Synthelabo Inc. 3 6 9 12 15 18 21 24 27 30 33 36
Months of Follow-up
Median follow-up = 1.91 years
*ITT analysis
ASA= aspirin; CAPRIE = Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events;
RRR = relative risk reduction.
CAPRIE Steering Committee. Lancet. 1996;348:

49. Subgroup Analysis CAPRIE No. Patients Patient with stroke 6431
Patient with MI 6302
Patient with PAD 6452
All patients 19,185
CAPRIE=clopidogrel vs. ASA in patients at risk of ischemic events. Subgroup analysis.
75 mg clopidogrel vs. 325 ASA. Entry –recent MI, stroke, or PAD. Endpoint MI, stroke, or other vascular death.
-40
-30
-20
-10 10 20 30 40
ASA Better
Clopidogrel Better
Risk Reduction (%)
CAPRIE Steering Committee. Lancet. 1996;348:

50. Leg Problems Asymptomatic No specific treatment Claudication
PAD Treatment
Leg Problems
Asymptomatic
No specific treatment
Claudication
Do nothing

51. Clinical Outcomes in Patients With PAD
PAD Patient
Asymptomatic
50%
Intermittent claudication
40%
Critical leg ischemia
10%
PAD outcomes
Cardiovascular
morbidity/mortality
(5-year outcomes)
Clinical Outcomes in Patients with PAD
Although PAD follows the same course in patients with vascular disease as it does in the general population, the percentage of affected individuals is higher. As noted here, half of all affected patients >55 years old are asymptomatic, whereas 40% experience intermittent claudication and 10% have critical leg ischemia. Five years after diagnosis, nearly three quarters of all claudicants remain symptomatically stable. A much smaller percentage (16%) experience worsening symptoms, and in 11% the situation deteriorates to the point where bypass surgery or amputation is needed.
While PAD itself is not generally life-threatening, there is a high associated morbidity and mortality from CVD and cerebrovascular disease. Five years after diagnosis, 20% of affected persons will have had a nonfatal stroke or MI and another 20% to 30% will have died from such events.
Nonfatal events
(MI/stroke)
20%
Mortality 30%
Stable claudication 73%
Worsening claudication 16%
Leg bypass surgery 7%
Major amputation 4%
Adapted from Weitz Jl. Circulation. 1996;94:

52. Leg Problems Asymptomatic Claudication Do nothing Walking program
PAD Treatment
Leg Problems
Asymptomatic
Claudication
Do nothing
Walking program
Best are supervised
Few programs available
Rarely reimbursable by insurance
Most patients must do their own

53. Walking Program Regular At least 5×/week Length 40-60 min/d
Claudication Treatment
Walking Program
Regular
At least 5×/week
Length
40-60 min/d
Typical results
Doubling of walking distance each year
Excuses
Pain, hills, cold, heat, rain, etc.

54. Walking Program Additional benefits Good for Heart Lungs Weight loss
Claudication Treatment
Walking Program
Additional benefits
Good for
Heart
Lungs
Weight loss
Muscles
See your neighborhood
See new areas
Their dog will love it (if they have one)

55. Walking Program Avoid negative walking programs Disability parking
Claudication Treatment
Walking Program
Avoid negative walking programs
Disability parking
Wheelchairs
Motorized carts

56. The Best Treatment, But Requires the Patient’s Commitment
Claudication Treatment
Walking Program
The Best Treatment, But Requires the Patient’s Commitment

57. Leg Problems Asymptomatic Claudication Walking program
PAD Treatment
Leg Problems
Asymptomatic
Claudication
Walking program
Drugs: pentoxifylline; cilostazol

58. Cilostazol PAD Treatment 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

59. Leg Problems PAD Treatment Asymptomatic Claudication Walking program
Drugs: pentoxifylline; cilostazol
Invasive: angioplasty/stenting; surgery

60. My Approach/Recommendations
Claudication
Walking program
Drug(s): cilostazol
Invasive: angioplasty/stenting; surgery

61. Leg Problems Asymptomatic Claudication Ischemic rest pain Refer
PAD Treatment
Leg Problems
Asymptomatic
Claudication
Ischemic rest pain
Refer
Nonhealing wounds/ulcers/tissue loss

62. Critical Limb Ischemia
PAD Treatment
Critical Limb Ischemia
These patients need revascularization
Angioplasty/stenting
Surgery
If revascularization is not possible
May need amputation

63. Case Study

64. 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

65. Patient Case Study Medical history Not on any medications
Once told his blood pressure was “a little high”
Doesn’t know his cholesterol or diabetes status
Has only sought medical care for acute problems in the past
Smoking history
Smokes 1-2 packs/d × 35 years

66. Patient Case Study Positive physical findings
Right arm systolic blood pressure: 160 mm Hg
Left arm systolic blood pressure: 152 mm Hg
Left carotid bruit
Absent right popliteal, PT, dorsalis pedis pulses
Right PT pressure: 80 mm Hg
Right AT pressure: 66 mm Hg
Left PT pressure: 135 mm Hg
Left AT pressure:140 mm Hg
AT = anterior tibial; PT = posterior tibial.

67. 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

68. ? Decision Point What etiology might account for unilateral
claudication?
Vascular disease limited to one leg
Bilateral vascular disease worse in one leg causing symptoms to appear earlier in one leg than another
Peripheral neuropathy due to diabetes
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69. 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

70. ? Decision Point What test(s) would you consider now?
Lipid, glucose, repeat ABI
Lipid, glucose, segmental pressures
Lipid, glucose, carotid duplex, and repeat blood pressure
Segmental pressures
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71. Patient Case Study He needs further evaluation
Repeat blood pressure checks
Blood tests: lipid panel, glucose
Carotid duplex
He needs treatment for his cardiovascular risks

72. Patient Case Study Treatment for his cardiovascular risks
Stop smoking: teach him how or refer
Probable blood pressure control
Lipids?
Diabetes?
Antiplatelet therapy

73. 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

74. Patient Case Study You describe the treatment options Walking program
Drug(s): cilostazol
Invasive: angioplasty/stenting; surgery

75. Q & A

76. PCE Takeaways

77. 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

78. ? Key Question Will you use ABI testing to diagnose patients
at risk for PAD?
Not likely
Somewhat likely
Very likely
Extremely likely
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