Mehul Bhatt, MD
Interventional Cardiology / Vascular Medicine
Athens Heart Center
Two Major Goals in Treating Patients With PAD
morbidity and mortality
Limb outcomes outcomes
Improved ability to walk • Decrease in morbidity from
non-fatal MI and stroke
Increase in peak walking
distance • Decrease in cardiovascular
mortality from fatal MI and
Improvement in quality-of-
Prevention of progression to
critical limb ischemia and
Treatment of critical limb
ischemia and amputation
Effect of Smoking Cessation on Survival
133 Patients observed after bypass graft or lumbar sympathectomy
Cumulative Survival (%)
20 Tobacco abstinence
Continued tobacco use
0 1 2 3 4 5
Faulkner KW, et al. Med J Aust. 1983;1:217-219.
Heart Protection Study:
Vascular Event by Prior Disease
Incidence of events
Statin Control Risk vs Control
Existing disease (n=10,269) (n=10,267) Statin Placebo
Previous MI 23.5 29.4
Other CHD 18.9 24.2
No prior CHD or CBV
PAD 24.7 30.5 (P<.0001)
Diabetes 13.8 18.6
All patients 19.8 25.2
0.4 0.6 0.8 1.0 1.2 1.4
CBD=cerebrovascular disease; CHD=congestive heart disease. Reprinted with permission from Heart Protection
Study Collaborative Group. Lancet. 2002;360:7-22 from Elsevier.
Considerations for the Treatment of Hypertension in
Blood pressure lowering is indicated to reduce
the risk of stroke, MI, CHF, CRF, and death.
Only major reductions in perfusion pressure
may worsen claudication (21 mm Hg decrease
in SBP resulted in a 9% decrease in absolute
Individuals with PAD should receive
hypertension treatment according to current
national guidelines (e.g., JNC-7).
CRF=chronic renal failure; CHF=congestive heart failure.
- Blockers Are Not
Contraindicated in PAD
In a meta analysis of 11 randomized
controlled trials beta-blocker therapy did
not worsen claudication in patients with
Beta blockers had no significant effect on
pain-free walking distance compared with
placebo in pooled analysis.
Radack K. Arch Intern Med. 1991;151:1769.
Antithrombotic Trialists’ Collaboration (ATC):
Meta-Analysis of Vascular Events in Antiplatelet Trials in Patients With PAD
Category APT CTRL Reduction (%)
Intermittent 6.4% 7.9% 23±9
Peripheral artery 5.4% 6.5% 22±16
Peripheral 2.5% 3.6% 29±35
All high-risk patients
0.0 0.5 1.0 1.5 2.0
Data from 197 randomized trials comparing an antiplatelet agent (APT; aspirin, clopidogrel,
dipyridamole, or a glycoprotein IIb/IIIa antagonist) vs control or another antiplatelet agent.
Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86.
Risk Reduction of Clopidogrel vs. Aspirin in
Patients With Atherosclerotic Vascular Disease
Aspirin favored Clopidogrel favored
-30 -20 -10 0 10 20 30 40
Reprinted with permission from CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.
Exercise Therapy (Supervised)
Frequency: 3–5 supervised sessions/week
Duration: 35–50 minutes of exercise/session
Type of exercise: treadmill or track walking
to near-maximal claudication pain
Length: 6 months
Results: 100%–150% improvement in maximal
walking distance and associated improvement
Stewart KJ et al. N Eng J Med. 2002;347:1941-1951.
Effects of Exercise Training
Meta-analysis of 21 Studies
180 * Exercise Training
Change in Treadmill Walking
* P < 0.05
Onset of Maximal
Claudication Pain Claudication Pain
Gardner AW, Poehlman ET. JAMA. 1995;274:975-980.
Cilostazol vs. Pentoxifylline:
Relative Efficacy to Improve Walking Distance in Claudication
Cilostazol 100 mg 2 times/day (n=227)
Pentoxifylline 400 mg 3 times/day (n=232)
Percentage Change From
Baseline MWD (mean)
Placebo (n=239) *
0 4 8 12 16 20 24
MWD=maximal walking distance.
*P<0.001 vs pentoxifylline.
Reprinted from Dawson DL, et al. Am J Med. 2000;109:523-530 with permission from Elsevier.
Contraindications to Cilostazol Use
Cilostazol and several of its metabolites are inhibitors
of phosphodiesterase III. Several drugs with this
pharmacologic effect have caused decreased survival
compared with placebo in patients with Class III-IV
CHF. PLETAL® is contraindicated in patients with CHF
of any severity.
“CHF of any severity” (systolic dysfunction)
Any known or suspected hypersensitivity to any of its
CHF=congestive heart failure.
Pletal® (cilostazol) Package Insert. Rockville, Md: Otsuka America Pharmaceutical, Inc; 1999.