Slide Kit 2

Peripheral Arterial DiseasePeripheral Arterial Disease

24.7%

3.8% 11.8%

29.9%

3.3%

7.4%

19.2%

Coexisting Vascular Diseases

CADCVD

PAD

Lancet. 1996;348:1329–39

Atherothrombosis is commonly found in more than one arterial bed.(CAPRIE study, n = 19,185)

CoexistentStroke

CoexistentPAD

CoexistentCAD

Co

exis

ten

t D

ise

ase

(%)

70

60

50

40

30

20

10

0

56

28

68

42

3226

CADPADCVD

Ness J. et al. J Am Geriatr Soc. 1999;47:1255-1256

CVD: Cerebrovascular Disease, CAD: Coronary Arterial Disease, PAD: Peripheral Arterial Disease

Long-Term observation of IC patients

Survival, myocardial infarction, surgical or percutaneous revascularization, and major amputation over 10 years of follow-up in patients initially presenting with intermittent claudication

Kenneth Ouriel. Lancet. 2001;358:1257-64

Time (years)

Pat

ien

ts (

%)

0 1 2 3 4 5 6 7 8 9 10

SurvivalMyocardial infarctionInterventionAmputation

100

80

60

40

20

0

Assumptions include a 6.8% annual risk of mortality, a 2.0% risk of myocardial infarction, a 1.0% risk of intervention, and a 0.4% risk of amputation.

Background

Diabetic MellitusHypertension

Hyperlipidemia

Level I Level II Level III Level IV

Symptoms by decrease of blood

flow

Decrease of function Ulcer and Necrosis

AsymptomaticNumbness Coldness

Raynaud’s phenomenon

IntermittentClaudication

Resting Pain

UlcerNecrosis

Patholophysiology of PAD

Peripheral arterial disease

Carotid artery (Brain)

Aorta (to body)

Superior mesenteric artery & celiac artery (Intestines)Renal artery (Kidneys)

Common iliac artery (Legs)

Ischemia:decreased oxygen-rich blood to an area, which can cause pain and dysfunction

Narrowed artery

Platelet

50% of diameter stenosis75% of area stenosis

60% of diameter stenosis 84% of area stenosis

Main arteries’ stenosis

Progress of stenosis ・ occlusion Occlusion

Major Symptoms of PAD

Rest pain Claudication

ColdnessAbnormal skin colorCold sensation in one or both legs/ hands

Pain in one or both legs on walking, primarily affecting the calves, that does not go away with continued walking and is relieved by rest

Occlusion of the lumen of 90% or more will likely produce pain even at rest .

Skin (of extremities) turns to a pale or purple color. Numbness sometimes appears together.

Erectile dysfunctionPeripheral Neuropathy

Other symptoms

Patients with PAD have a reduced functional capacity that limits their ability to perform daily activities.

PAD is often Asymptomatic

Newly diagnosis of PAD (n = 457) No (%)

Prior diagnosis of PAD(n = 366) No (%) p value

No pain 193 (48.3 %) 84 (25.8 %) < 0.001

Atypical 185 (46.3 %) 201 (61.7 %) < 0.001

Classic rose claudication 22 (5.5 %) 41 (12.6 %) < 0.001

ABPI (SD) 0.78 (0.16) 0.78 (0.23) < 0.001

Leg symptoms: PARTNERS

Vasc Med. 2001;6Suppl 1:9-12JAMA. 2001;286(11):1317-1324

• Rose claudication: exercise induced calf pain, not present at rest, which required stopping, and remitted in 10 minutes or less.

• Prevalence of PAD in primary care practice is high, yet physician awareness of the PAD diagnosis is relatively low. Underdiagnosis of PAD maybe a barrier to effective secondary prevention of the high ischemic cardiovascular risk associated with PAD.

PAD: ABPI ≤ 0.90

Risk factorsIntermittent claudication

with without Odds Ratio p value

Male sex (%) 56 42 1.7 0.0001

Mean age (y) 64 60 1.5 0.0001

High-normal blood pressure (%) 16 19 1.3 0.1302

Stage 1 hypertension (%) 29 28 1.5 0.4164

Stage 2 hypertension (%) 36 22 2.2 0.0001

Diabetes (%) 20 6 2.6 0.0001

Daily cigarette smoking rate 10 7 1.4 0.0001

Mean cholesterol (mg/dL) 248 239 1.2 0.0018

Preexisting CHD (%) 34 12 2.7 0.0001

Risk factors by intermittent claudication status

Statistics based on 26,316 person-examinations (381 with IC and 25,935 without IC).Stage 1 hypertension: systolic blood pressure 140-159 mmHg; diastolic blood pressure 90-99 mm Hg.Stage 2 hypertension: systolic blood pressure 160 mmHg; diastolic blood pressure 100 mm Hg. CHD: Coronary Heart Disease

Joanne M Murabito et al. Circulation. 1997;96:44-49

Risk Factors of intermittent claudication

Evaluation of PAD

Age 50–69 years and smoking or diabetesAge 70 yearsLeg pain with exertion Abnormal results on vascular examination of legCoronary, carotid, or renal arterial disease

Measure ankle-brachial index

Index 0.91 ~ 1.30 Index 0.90Index > 1.30

Pulse-volume recordingToe-pressure measurementDuplex ultrasonography

Measure ankle-brachialindex after treadmill test

Normal results:no peripheral

arterial diseaseAbnormal results

Normal postexerciseankle-brachial index:

no peripheralarterial disease

Decreasedpostexercise

ankle-brachial index

Evaluate other causesof leg symptoms

Peripheral arterial disease

Hiatt WR. N Engl J Med, 2001;344(21):1608-21

Symptomatic Outcome Measures

Classification of PAD:Fontaine’s Stages and Rutherford’s categories

Fontaine Rutherford

Stage Symptom Grade Category Clinical Description

I Asymptomatic 0 0 Asymptomatic

IIa Mild claudication I 1 Mild claudication

IIbModerate severe

claudication

I 2 Moderate claudication

I 3 Severe claudication

III Ischemic rest painII 4 Ischemic rest loss

III 5 Minor tissue loss

IV Ulceration or Gangrene III 6 Major tissue loss

J Vasc Surg. 2000;31(1 part 2):S38-S39Am J Cardiol. 2001;87(12A):3D-13D

Grade Category Clinical Description

0 0 Asymptomatic

I 1 Mild claudication

I 2 Moderate claudication

I 3 Severe claudication

II 4 Ischemic rest loss

III 5 Minor tissue loss

III 6 Major tissue loss

Objective Outcome Measures- ABPI (Ankle Brachial Pressure Index)

Left-armsystolic pressure

DPPT

Right-anklesystolic pressure

DPPT

Left-anklesystolic pressure

Interpretation of ABPI

> 1.30 Non compressible

0.91-1.30 Normal

0.41-0.90 Mild-to-moderate PAD

0.00-0.40 Severe PAD

Left ABI =

Higher left-ankle pressure

Higher arm pressure

Right ABI =Higher right-ankle pressure

Higher arm pressure

DT: Dorsalis Pedis, PT: Posterior Tibial Hiatt WR. N Engl J Med. 2001;344(21):1608-21

Doppler flowmeter

Pulse Wave Velocity (PWV)

PWV(cm/sec) =

Distance to be measured

Pulse Wave Transmit TimeDistance

Artery

A B

Time

Stiffness

PWVHigh

Low

Soft Hard

AsymptomaticGroup

(Gray Zone)Symptomatic

Group(Abnormal)

Normal

Increase of PWV shows constant increase for risks of coronary heart disease, stroke and cardiovascular disease.

Peripheral Vascular Disease

PVD Type Vessels involved

Peripheral atherosclerotic disease

Atherosclerotic Large and medium sized arteries

Burger’s disease Inflammatory and thrombotic Small and medium sized arteries and veins

Raynaud’s disease Vasospastic Arterioles

Acute arterial occlusion Hemolytic and thrombotic Arteries

Fibromuscular dysplasia

Hyperplastic, with or without thrombus formation

Small and medium sized arteries

Thrombophlebitis (Superficial phlebitis) Inflammatory and Thrombotic Superficial veins

Deep vein thrombosis Embolytic and thrombotic Deep veins

Varicose veins Structural defect Leg veins

• Inflammation and thrombus formation in the small and medium-sized arteries and in the superficial veins of the extremities

• More commonly in the legs than in the arms

• Cigarette smoking is highly associated

• More frequent incidence in men under age 40

• Intermittent claudication, superficial phlebitis

• Sensation of coldness, numbness, abnormal skin color, ulcerations, necrosis and gangrene in the tips of the fingers

Buerger's Disease

Overview

Manifestations

Treatment• Incurable/ slow progression

• Elimination of Smoking

• Prevention of local tissue damage from cold temperatures, trauma, fungal infections

• Vasospasm-induced ischemia of the arterioles in the fingers and toes, and occasionally of the nose and tongue

• Raynaud’s disease (primary): without underlying medical problem

• Raynaud’s phenomenon (secondary): with underlying medical problem

• Triphasic color reaction: Red white blue

• Pain, throbbing sensation and extreme coldness of hands

Raynaud's Disease / Phenomenon

Overview

Manifestations

Treatment• Protection from cold

• Mild sedative, prazosin, nifedipine, pentoxifylline

• Relaxation technique

• Cessation of smoking to prevent vasoconstriction

Intermittent Claudication

Intermittent claudicationWhen walking, pain occurs, but it is gone with resting

Maximal walking speed

Maximal walking distance

Peak VO2 (Oxygen consumption)

• Normal = 3 - 4 mph• PAD = 1 - 2 mph

• Normal = unlimited• PAD, 31% difficulty walking in home • PAD, 66% difficulty walking ½ block

• PAD, reduced 50%

Otsuka data set. WR Hiatt et al. J Appl Physiol. 1992;73:346-353

Differentiation from Neural Disorder

Neural disorder lumbar spinal canal stenosis is very similar with IC

Vascular (IC)

Pain when walking

Stiffness at foot when walking for 4~5 mins.

Neural(Lumbar Spinal Canal Stenosis)

Pain varied by the motion

Not dependent on the distance, irregularly occurs

監修：済生会福岡総合病院院長　岡留健一郎

Am J Cardiol. 2001;87 (suppl):3D-13D

What cause intermittent claudication?

Atherosclerosis in peripheral arteries of legs

Lactic acid and other metabolites washed away on rest

During exercise, oxygen demand increases

Muscles operate anaerobically

Produce lactic acid and other metabolites

Leg pain

Pathogenesis of Intermittent ClaudicationHemodynamic Abnormalities

Pathogenesis of Intermittent ClaudicationMetabolic and Neurological Abnormalities

Creager M, ed. Management of Peripheral Arterial DiseaseMedical, Surgical, and Interventional Aspects. 2000

Oxidative injury to

mitochondrial DNA

Accumulation of metabolic

intermediates

Increased mitochondrial

expression

Denervation and loss of mus

cle fibers

Reduced lower-

extremity perfusion

Intermittent Claudication

Decreased quality of life

Limit activities of daily livingLimit recreational activitiesPossible amputation(s) with progression of underlying PAD

Decreasedlife expectancy

PAD shortens life expectancy by 10 years

Increased mortality rate

3 fold increased risk of death from all causes and 6 fold increase in risk of cardiovascular related death in patients with large vessel PAD compared with age and gender-matched patients with same risk factors but without PAD

Consequences of IC/PAD

Natural history of IC/PAD• 75% experience symptom

stabilization or improvement.

• 15-20% require revascularization (angioplasty or bypass surgery)

• 2~4% require amputation

• Death is usually due to coexisting coronary artery or cerebrovasculardisease, not PAD

Am J Cardiol. 2001;87 (suppl):3D-13D

Follow-up (years)0 5 10 150

20

40

60

80

100

IC

Control

Su

rviv

al

(%)

日本脈管学会編：「下肢閉塞性動脈硬化症の診断・治療指針」、協和企画： p20,2000

Obstructive lesion %* Ischemia in

Aorta or iliac 30 %

Buttock

Hip

Thigh

Femoral or popliteal 80-90 %Thigh

Calf

Tibial or peroneal 40-50 %

Calf

Ankle

Foot

*Percent of IC patients who have an obstructive lesion in the site

Common iliac artery

Femoral artery

Popliteal artery

Anterior tibial artery

Posterior tibial artery

Dosalis pedis artery

Sites of Occlusion and Pain

Internal iliac arteryExternal iliac artery

Deep Femoral artery

Peroneal artery

Lower Limb Pulse Examination Point

平井都始子 他　 Medical Technology. 1997;25(5):460-461

Lower limb arteries

① Common iliac artery② Internal iliac artery③ External iliac artery ④ Deep femoral artery⑤ Superficial femoral artery⑥ Popliteal artery⑦ Anterior tibial artery⑧ Dorsalis pedis artery ⑨ Posterior tibial artery

①②

③

④

⑤

⑥

⑦

⑨

⑧

No4

No5

No3

No2

No1Femoral artery Femoral vein Popliteal artery

Dorsalis pedis artery

Posterior tibial artery

Characteristics of Common Ulcers

HL Moore and JV white. PAD Handbook, CRC Press, 2005

Arterial (Ischemic)

Main arteries

Venous stasis

Venous disease

Neurotropic (Diabetic)

Neuropathy

Venous Neutrophic

PAD, Burger’s Acute occlusion

Toes, foot MalleolarSole and pressure p

oints of foot

Severe Mild None

Irregular, pale base Irregular, pink base Often deep, infected

Origin

Cause

Location

Pain

Appearance

Diabetic foot ulcer

• The annual population-based incidence ranges from 1.0% to 4.1%1 and the prevalence ranges from 4% to 10%, which suggests that the lifetime incidence may be as high as 25%.2,3

• Diabetes underlies up to 8 of 10 nontraumatic amputations, of which 85% follow a foot ulcer.2

Epidemiology of diabetic foot ulcer

Pathophysiology of diabetic foot ulcer

• Peripheral Neuropathy• Excessive plantar pressure• Trauma, especially when

repetitive

• Atherosclerotic peripheral vascular disease

• Intrinsic wound-healing disturbance

• A higher rate of onychomycosis

Causative Factors Causative Factors Contributory Factors Contributory Factors

Diabetic Foot Ulcer JAMA. 2005;293:217-228

Improve functional

status

Preserve the limb

Prevent progression ofatherosclerosis

Reduce cardiac and

cerebrovascular mortality

To address the risk in cardiovascular events

To address limb symptoms

Clinical Treatment Goals of PAD

Reduce clinicalevents such as MI

and stroke

Decrease the need for

revascularization and amputation

Improve symptoms

Improve QOLImprove exercise

capacity

Cardiovascular Risk Modication

Effect of cardiovascular risk modification therapies on claudication symptoms

Treatment Claudication Symptoms

Lipid lowering drugs + improvement

Smoking Cessation +/- improvement

ACE Inhibitors No improvement

Antiplatelet Therapies No improvement

Diabetes Treatment No improvement

Hypertension Treatment Worsen

ACE: Angiotensin Converting EnzymeHiatt WR. Curr Drug Targets Cardiovasc Haematol Disord. 2004 Sep;4(3):227-31

Treatment that reduce cardiovascular risk generally do not improve claudication symptoms.

Treatment of PAD

Adjuvant therapy: Exercise, MedicationIntravascular treatment: Minimally invasive treatment using catheter or stentSurgical treatment: Bypass

Treatment of peripheral arterial disease

Fontaine classification

Exercise Medication

Risk factor Reduction

Intravascular treatment Medication

Surgical treatmentIntravascular treatment

Medication

監修／星野俊一　ほか：日常みられる下肢閉塞性動脈硬化症の診療ガイドブック , p23, キタメディア , 2002

Level I Level II Level III Level IV

Introduction of TASC

Number 1, Part 2:S93

VASCULAR

Management of Peripheral Arterial Disease (PAD)TransAtlantic Inter-Society Consensus (TASC)

TASC

SURGERY

J O U R N A L O FSUPPLEMENT TO

VOLUME 31 NUMBER 1 PART 2 JANUARY 2000

Mosby

Section A: IntroductionSection B: Intermittent Claudication

Section C: Acute Limb IschemiaSection D: Critical Limb Ischemia

Developed by theTASC Working Group

In order to ensure an appropriate management algorithms and to achieve the optimal outcome for PAD patients, a group of experts in managing these patients had formulated the TransAtlantic Inter-Society Consensus (TASC). The TASC Working Group consisted of 14 MD societies across United States & Europe who had formulated the TASC Guidelines in the management of PAD based in current evidence-based medicine.

J Vasc Surg. 2000;31(1 Part 2):S1-S296

• 107 Recommendations• 47 Critical Issues

Complete Management Algorithm

History and physical examinationAnkle-brachial pressure indexConfirmation PAD with intermittent claudication

Assess cardiovascular risk factors ＋ Assess disability symptom severity

Special investigations: ･ Hyper-coagulability scree

n ･ Homocysteine level ･ LP （ a ） ･ Other

･ Modify risk factors ･ Antiplatelet therapy

SF-36 ＝ medical outcomes Short Form 36 questionnaireWIQ ＝ Walking Impairment QuestionnairePVR ＝ Pulse Volume RecordingVWF ＝ Velocity Waveform AnalysisMRA ＝ Magnetic Resonance Angiography * disability as defined by the individual patient

Encourage supervised walking exercise program/ consider pharmacotherapy

Locate lesion using: ･ Segmental limb pressure ･ PVR or VWF ･ Duplex scanning ･ MRA

TransAtlantic Inter-Society Consensus : TASC

Mild symptoms-not disabled

Moderate symptoms-disabled

Severe symptoms-disabled

Continue Successful outcome unsuccessful

Continue noninvasive measures

Endovascular or surgical therapy

Treadmill and/or・ SF-36 questionnaire・ WIQ questionnaire

Initial evaluation ･ Hemoglobin ･ Serum creatinine ･ Smoking ･ Lipid profile ･ Hypertension ･ Diabetes

J Vasc Surg. 2000;31(1 Part 2):S1-S296

Potential Favorable Effects of Exercise Training

↑ Nitric oxide synthase

↑ Prostacyclin

↓ Free Radical

↑ Vascular Endothelial Growth Factor

↑ Muscle oxidative activity

↑ Muscle enzyme activity

↑ Muscle acylcarnitine homeostasis

↓ Blood viscosity ↑ RBC filterability

↓ RBC aggregation

Exercise Training

Improved endothelial function

Reduced Inflammation

Possible vascular angiogenesis

Improved muscle metabolism

Improved hemorheology

N Eng J Med. 2002;347(24):1941-1951

Risk Factor Modification (TASC)

Recommendation 22 Smoking cessation in peripheral arterial disease

Recommendation 23 Control of diabetes in peripheral arterial disease

Recommendation 24 Diabetic foot care in peripheral arterial disease

Recommendation 25 Lipid control in peripheral arterial disease

Recommendation 26 Control of hypertension in peripheral arterial disease

Recommendation 27 Hypercoagulable states in intermittent claudication

Recommendation 7 Hyperhomocysteinemia in peripheral arterial disease

J Vasc Surg. 2000;31(1 part 2):S1-S296

Pharmacotherapy (TASC) to address the marked increase risk in cardiovascular events

Antiplatelet in PADAll patients with peripheral arterial disease (whether symptomatic or asymptomatic) should be considered for treatment with low-dose Aspirin or other approved antiplatelet (unless contraindicated), to reduce the risk of cardiovascular morbidity and mortality.

J Vasc Surg. 2000;31(1 Part 2): S1-S296

Recommendation 28

Ticlopidine

Clopidogrel

• Ticlopidine has been shown to reduce the risk of stroke and fatal and nonfatal myocardial infarction by 29% compared with placebo.

J Intern Med. 1990;227:301-8

• In CAPRIE study, Clopidogrel showed an overall RRR 8.7% in the risk reduction compared to Aspirin among the total population of more than 3,000 patients in each group (P = 0.04).

• In the PAD subgroup, clopidogrel (as compared with aspirin) resulted in a 23.8% relative risk reduction of ischemic stroke, MI, or vascular death, although the 95% confidence interval was wide (8.9%-36%).

Lancet. 1996;227:301-308

Recommendation 30

Pharmacotherapy for symptoms of intermittent claudication

• Although some controlled clinical trials with Pentoxifylline, Naftidrofuryl, Buflomedil, and recently Cilostazol (Pletaal®), have shown statistically significant improvement in walking distance, the average benefit was small. Greater benefit, observed in minority of patients, may warrant a short course of therapy with continued use of such agents if sufficient benefit is observed.

• Recent clinical trials have shown a greater benefit of Cilostazol (Pletaal®), for both walking distance and quality of life, which may warrant more widespread use. However, currently there are insufficient data to recommend the routine use of pharmacotherapy in all patients with claudication.

Pentoxifylline, Naftidrofuryl, Buflomedil, Pletaal

J Vasc Surg. 2000;31(1 Part 2):S1-S296

Pharmacotherapy (TASC)-2000 Established Drugs with Proven but Small Benefit in Improving Claudication

• Aspirin: No studies have shown a benefit of Aspirin in the treatment of claudication, although there is one study that presented suggestive evidence that Aspirin slowed progression of atherosclerosis assessed by serial angiography.

• Ticlopidine: Ticlopidine may reduce the severity of claudication and the need for vascular surgery.

Balsano F. J Lab Clin Med. 1989;114:84-91, Eur J Vasc Endovasc Surg. 1995;10:69-76

Antiplatelet drugs (Aspirin/Ticlopidine)

Pharmacotherapy (TASC)-2000 Drugs With Minimal or No Benefit in Improving Claudication

J Vasc Surg. 2000;31(1 Part 2):S1-S296

Vasodilators• α blockers, papaverine, β2 agonist, calcium channel blocker, angiotensin

converting enzyme inhibitor

• Arteriolar vasodilators were the first class of agents used to treat claudication. These drugs have not been shown to have clinical efficacy in randomized, controlled trials.

BMJ. 1991;303:1100-1104, N Engl J Med. 1979;300:713-717, J Vasc Med Biol. 1993;4:23-28

Others• Ketanserin, Verapamil, Isovolemic hemodilytion, Amiophylline, Vitaime E, Defibrotide

Supplementation of patients with carnitine improves ischemic muscle metabolism. Carnitine, and an acyl form of carnitine (propionyl-l-carnitine), are drugs that have been shown to increase exercise performance and improve claudication symptoms in several clinical trials.

Carnitine

Pharmacotherapy (TASC)-2000 Incompletely Studied Drugs With Potential Benefit in Improving Claudication

J Vasc Surg. 2000;31(1 Part 2):S1-S296

ProstaglandinsCritical Issue 8: There is a need to investigate the possibly greater efficacy of prostanoids in patients with intermittent claudication, because most randomized, open or double-blind trials with intra arterial or intravenous prostanoids have been performed in patients with the last stage of critical limb ischemia. Predictors to select the most suitable patients for prostanoid treatment need to be determined.

Vascular endothelial growth factor (VEGF)

Early phase I and phase II trials are now in progress to determine whether this novel therapy has a clinical application in patients with claudication and severe leg ischemia.

Cilostazol (Pletaal®), 2005 (TASC)

Recommendation 16:

Pharmacotherapy for symptoms of intermittent claudication

A 3- to 6-month course of Pletaal should be first-line pharmacotherapy [B] for the relief of claudication symptoms, as evidence shows both an improvement in treadmill exercise performance and in quality of life [A]. Controlled data also support the efficacy of Naftidrofuryl [A] and only minimally support the efficacy of pentoxifylline [A].

Cilostazol (Pletaal®)

ProstaglandinsSeveral studies have been performed with oral Beraprost. While there was a positive trial in Europe, there have been two negative trials in the USA (Labs et al. 1999; Lievre et al. 2000; Mohler et al. 2003b). While intravenous administration of PGE1 may have modest benefits, the overall evidence does not support the use of this drug class for claudication (Reiter et al. 2004).

Publication: 2005Representative of AsiaProf.H. Shigematsu,Tokyo Univ.

Antithrombotic therapy in peripheral arterial occlusive disease:Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

ACCP: American College of Chest Physicians CHEST. 2004 Sep;126(3 Suppl):609S-626S

1. Aspirin

We recommend lifelong aspirin therapy, 75 to 325 mg/d, in comparison to no antiplatelet therapy in patients with clinically manifest coronary or cerebrovasculardisease (Grade 1A) and in those without clinically manifest coronary or cerebrovascular disease (Grade 1C).

2. Ticlopidine

We recommend clopidogrel over ticlopidine (Grade 1C).

3. Clopidogrel

We recommend clopidogrel in comparison to no antiplatelet therapy (Grade 1C), but suggest that aspirin be used instead of clopidogrel (Grade 2A).

Chronic Limb Ischemia (ACCP)

4. Cilostazol (Pletaal®)

• For patients with disabling intermittent claudication who do not respond to conservative measures (risk factor modification and exercise therapy) and who are not candidates for surgical or catheter-based intervention, we suggest Pletaal (Grade 2A). We suggest that clinicians not use Pletaal in those with less-disabling claudication (Grade 2A).

• Underlying values and preferences: The recommendation against Pletaal for those with less-disabling claudication places a relatively low value on small possible improvements in function in the absence of clear improvement in health-related quality of life.

Chronic Limb Ischemia (ACCP)

5. Pentoxifylline

We recommend against the use of pentoxifylline (Grade 1B).

6. Prostaglandins

For limb ischemia, we suggest clinicians not use prostaglandins (Grade 2B).

Underlying values and preferences: The recommendation places a low value on achieving small gains in walking distance in the absence of demonstrated improvement in quality of life. ACCP: American College of Chest Physicians

CHEST. 2004 Sep;126(3 Suppl):609S-626S

Pharmacotherapy (American Family Physician)

Drugs Dosage Comments

Aspirin 81-325 mg qdRecommended by the American College of chest Physicians for PAD, but the FDA found insufficient evidence to approve labeling for this indication

Clopidogrel 75 mg qdFewer side effects than aspirin in the CAPRIE trial, significantly less risk for TTP than ticlopidine

Pentoxifylline 400 mg tidMay have a small effect on walking ability, but insufficient data to support widespread use

Cilostazol

(Pletaal®) 100 mg bid

• Correct dosing is critical• Avoid in patients with heart failure• Reduce dosing to 50 mg twice per day in

patients taking calcium channel blockers• May cause loose stools and gastric upset

Ticlopidine 500 mg bid Extensive hemodynamic monitoring for risk of TTP

Am Fam Physician. 2004 Feb 1;69(3):525-32

Role of Pletaal in PAD

Drug of Choice for the treatment of PAD

Inhibition of thrombus formation

↓ Platelet aggregation

Vascular normalization

Endothelium protectionAntiproliferation on VSMC

Promote Angiogenesis

Lipid metabolism improvement

↓ TG ↑ HDL

↓ ApoB ↓ RLP ↑ DHA

Blood flow improvement

↑ Vasodilation (High femoral artery selectivity)

↑ RBC deformability

Improvement of Symptom

Risk factor Modification

+

Improving QOL among PAD or IC patientsAddressing the increase risk in cardiovascular eventsPrevention of Diabetic complication