1. Medical Management of Claudication: Just Walk it Off!!
Amjad AlMahameed, MD
Director, Vascular Medicine Research
Associate Staff, Section of Vascular Medicine
Department of Cardiovascular Medicine
Cleveland Clinic Foundation

2. Objectives Recognize the magnitude of PAD as a public health problem
Review best management strategies
Reflect on future prospects

3. Natural History of Intermittent Claudication
Population > 55 y/o
Intermittent Claudication (5%)
Cardiovascular
Cause
75%
Nonfatal CV Event
MI/Stroke/other
20%
5 year
Mortality
30%
Other Cardiovascular
Morbidity/Mortality
Peripheral Vascular Outcomes
Stable
Claudication
50-75%
Worsening
Claudication
17-25%
Lower Ext
Bypass 7%
Major
Amputation 4%
Serious, but “not so bad overall”….
Adapted from Weitz JI et al, Circulation 1996, 94:3026 and TASC Working Group J Vasc Surg 2000;31:(suppl 1) S1-296

4. PAD Survival* as a Factor of Clinical Severity
100
Normal Subjects 75
Asymptomatic LV-PAD†
Survival (% of patients) 50
Symptomatic LV-PAD†
Criqui et al conducted a study to evaluate the mortality rate from all cardiovascular diseases and coronary heart disease in patients with large-vessel peripheral arterial disease. In the initial screening of 565 patients, 67 patients (11.9%) with PAD were identified by noninvasive testing (measurement of segmental blood pressure and determination of flow velocity by Doppler ultrasound). These patients were then followed prospectively for 10 years.
Results revealed a 15-fold increase in rates of mortality due to cardiovascular disease and coronary heart disease among patients with PAD that was both severe and symptomatic. The survival curves for patients with PAD demonstrate a poor prognosis for these patients. Although there appears to be a direct relationship between severity of disease and reduction in survival, even asymptomatic patients have lower survival rates compared with healthy subjects. After 10 years, about half of asymptomatic patients survive, whereas only 25% of severely symptomatic patients survive.
Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326: 25
Severe Symptomatic LV-PAD† 2 4 6 8 10 12
Year
*Kaplan-Meier survival curves based on mortality from all causes. †Large-vessel PAD. Criqui MH et al. N Engl J Med. 1992;326:

5. The diagnosis of established atherosclerosis in a patient, or identifying that a patient is high risk for atherosclerosis is an: EVENT
event

6. for revascularization
Treatment Goals in PAD
Improve Functional
Status
Save the Limb
Prevent
Atherosclerosis
Progression
Reduce Cardiac
& Cerebrovascular
Morbidity/Mortality
Improve symptoms
Improve QOL
Improve exercise
capacity
Decrease the need
for revascularization
Systemic Therapy
“Ongoing research”
Record nonfatal
events (MI/CVA)
Weitz JI et al. Circulation 1996; 94: 3026

7. Smoking Cessation Strategies Repeated advice Nicotine replacement Rx
Benefits
Repeated advice
Nicotine replacement Rx
+/- Bupropion
Behavioral therapy: smoking cessation classes and support groups
Cessation leads to a reduction in 10 year mortality from 54% to 18%
Rest pain developed in 0% of quitters compared 16% of continued smokers at seven years

8. CAPRIE: Clopidogrel in Diabetes38 25 21
21.5% 9 20
17.7%
Clopidogrel
17.7%
15.6%
Aspirin 15
Annual
event
rate (%)
12.7%
11.8%
Events* prevented/ patients
over Aspirin 10
This figure illustrates that both patients with and without diabetes received a greater benefit with clopidogrel than with Aspirin.1
1. Bhatt D, Marso S, Hirsch A, Ringleb P, Hacke W, Topol E. Amplified benefit of clopidogrel versus aspirin in patients with diabetes mellitus. Am J Cardiol;90: 5
Nondiabetic
All diabetic
patients
Insulin-treated
* Events=vascular death, MI, stroke, or re-hospitalization for ischemia or bleeding.
Bhatt DL, et al. Am J Cardiol. 2002;90:

9. Statin Therapy Strategies Benefits of Statin Rx
All pts should be on a statin to achieve a 25% reduction in cholesterol
Additional treatment may be needed if HDL is low or TG are high
Remember that HDL and TG (+/- usCRP) are becoming therapeutic targets
RR=0.81(0.72 to 0.87) for major vascular events (MI, CVA, or revascularization)
Improved leg functioning, pain-free walking distance, and community-based physical activity independent of cholesterol level

10. Intensive BP therapy in PAD
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
1.10
1.20 10 20 30 40 50 
Odds of MI, Stroke, or Vascular Death 
Moderate Rx
Intensive Rx            
Baseline ABI

11. Relative Risk in Ramipril Group
ACE-I: HOPE Study
No. of Patients
Incidence of Composite Outcome in Placebo Group
PAD
4051
22.0
No PAD
5246
14.3
0.6
0.8
1.0
1.2
Relative Risk in Ramipril Group
HOPE Study Investigators N Eng J Med, 2000, 342:143

12. Increasing Walking Distance

13. Treatment of IC with Exercise Program
Meta Analysis # 1
49 publications, > 600 pts
Statistically significant increase in:
- Initial claudication distance:
139 meters
- Absolute claudication distance: 176 meters
Meta analysis # 2:
33 publications
Statistically significant increase in:
- Initial claudication distance:
179% from / m
to / m
- Absolute claudication distance:
122% (from /
m to / m)
CONCLUSIONS--The optimal exercise program for improving claudication pain distances in patients with peripheral arterial disease uses intermittent walking to near-maximal pain during a program of at least 6 months. Such a program should be part of the standard medical care for patients with intermittent claudication.
JAMA Sep 27;274(12):
Archives of Intern Med 1999, 159: 337

14. Relative Efficacy of Hospital vs
Relative Efficacy of Hospital vs. Home-Based Exercise Training (Regensteiner Angiology, 1997, 48:291)
Improvement in:
Supervised (N = 10)
Unsupervised (N = 10)
Peak walking time
137% 5%
Pin free walking time
26%
150%
Peak O2 consumption
19% 9%
Physical functioning
38%
16%
Walking distance
77%
42% (P<0.05)
Functional status evaluated by Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study SF-20 questionnaire (MOS).

17. Indications for Angiography in patients with PAD
Rest pain
Non-healing ulcers
Lifestyle-limiting claudication