The Peripheral Artery Disease Guideline:

Evidence-Based Management of Patients With PAD Core Curriculum Slide Set

A Collaborative Product Co-Developed by: American College of Cardiology; American Heart Association; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung and Blood Institute; Peripheral Artery Disease Coalition; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society for Vascular Nursing; Society for Vascular Medicine and Biology; Society for Vascular Surgery; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation.

The Peripheral Artery Disease Task to be Accomplished Is Encompassed in the Title:

ACC/AHA Guidelines for the Management of Patients With Peripheral Artery Disease:

A Collaborative Report from the

American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine and Biology, and the ACC/AHA Task Force on Practice Guidelines. Also endorsed by the: American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and The Vascular Disease Foundation.

Supported by an educational grant from Bristol-Myers Squibb and Sanofi Pharmaceuticals Partnership.

Bristol-Myers Squibb and Sanofi Pharmaceuticals Partnership were not involved in the development of this slide set and in no way influenced its contents.

Contributors

The PAD Guidelines Implementation Task Force Slide Set Co-Editors

Mark A. Creager, MD, & Alan T. Hirsch, MD

Alan T. Hirsch, Co-Chair Vascular Medicine/Cardiology Carolyn Robinson, NP, Co-Chair, Vascular Nursing

Thomas A. Biggs, MD Frank C. Brosius, III, MD Mark A. Creager, MD James B. Froehlich, MD, MPH William R. Hiatt, MD Karen Lui, RN, MS Timothy Murphy, MD Jeffrey W. Olin, DO

Harvey M. Wiener, DO, Co-Chair, Interventional Radiology John White, MD, Co-Chair, Vascular Surgery

Arthur L. Riba, MD Kerry J. Stewart, EdD Diane Treat-Jacobson, RN, PhD Rose Marie Robertson, MD Mark Sanz, MD Peter Sheehan, MD H. Eser Tolunay, PhD Christopher White, MD

Special Thanks to

The PAD Guidelines Writing Committee Members Alan T. Hirsch, MD, FACC, FAHA, Chair Ziv J. Haskal, MD, FAHA, FSIR, Co-Chair, Norman R. Hertzer, MD, FACS, Co-Chair

Curtis W. Bakal, MD, MPH, FAHA Mark A. Creager, MD, FACC, FAHA Jonathan L. Halperin, MD, FACC, FAHA Loren F. Hiratzka, MD, FACC, FAHA, FACS William R.C. Murphy, MD, FACC, FACS Jeffrey W. Olin, DO, FACC Jules B. Puschett, MD, FAHA Kenneth A. Rosenfield, MD, FACC David Sacks, MD, FACR, FSIR James C. Stanley, MD, FACS, FACR, FSIR Lloyd M. Taylor, Jr., MD, FACS Christopher J. White, MD, FACC, FAHA, FSCAI John White, MD, FACS Rodney A. White, MD, FACS

Applying Classification of Recommendations and Level of Evidence

Class I

Benefit >>> Risk

Procedure/ Treatment

SHOULD

be performed/ administered

Class IIa

Benefit >> Risk Additional studies with focused objectives needed

IT IS REASONABLE

to perform procedure/administer treatment

Class IIb Class III

Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful

Procedure/Treatment

MAY BE CONSIDERED

Risk ≥ Benefit No additional studies needed

Procedure/Treatment should

NOT

be performed/administered

SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

should is recommended is indicated is useful/effective/ beneficial is reasonable can be useful/effective/ beneficial is probably recommended or indicated may/might be considered may/might be reasonable usefulness/effectiveness is unknown /unclear/uncertain or not well established is not recommended is not indicated should not is not useful/effective/beneficial may be harmful

Applying Classification of Recommendations and Level of Evidence

Class I Class IIa Class IIb Class III

Benefit >>> Risk Benefit >> Risk Additional studies with focused objectives needed

Procedure/ Treatment

SHOULD

be performed/ administered

IT IS REASONABLE

to perform procedure/administer treatment

Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Risk ≥ Benefit No additional studies needed

Procedure/Treatment

MAY BE CONSIDERED

Procedure/Treatment should

NOT

be performed/administered

SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

Level A Multiple (3-5) population risk strata evaluated

General consistency of direction and magnitude of effect

Level B

Limited (2-3) population risk strata evaluated

Level C

Very limited (1-2) population risk strata evaluated

Why a PAD Guideline?

• • • • • To enhance the quality of patient care Increasing recognition of the importance of atherosclerotic lower extremity PAD: – High prevalence – High cardiovascular risk – Poor quality of life Improved ability to detect and treat renal artery disease Improved ability to detect and treat abdominal aortic aneurysm The evidence base has become increasingly robust, so that a data-driven care guideline is now possible

PAD Guideline:

The Target Audiences Are Diverse

• Primary care clinicians – – – Family practice Internal medicine PA, NP, nurse clinicians • Cardiovascular/vascular medicine, vascular surgical, & interventional radiology trainees • Vascular specialists

This is not intended to be a procedural guideline; it is intended to provide a guide to optimal lifelong PAD care.

PAD Epidemiology

Prevalence of PAD

NHANES 1 Aged >40 years San Diego 2 Mean age 66 years 4.3% NHANES 1 Aged 70 years Rotterdam 3 Aged >55 years 11.7% 14.5% Diehm 4 Aged 65 years PARTNERS 5 Aged >70 years, or 50–69 years with a history diabetes or smoking

0% 5% 10% 15%

19.1%

20%

19.8%

25%

In a primary care population defined by age and common risk factors, the prevalence of PAD was approximately one in three patients 29%

30% 35%

NHANES=National Health and Nutrition Examination Study; PARTNERS=PAD Awareness, Risk, and Treatment: New Resources for Survival [program].

1. Selvin E, Erlinger TP.

Circulation

. 2004;110:738-743.

2. Criqui MH, et al.

Circulation

. 1985;71:510-515.

3. Diehm C, et al.

Atherosclerosis

. 2004;172:95-105. 4. Meijer WT, et al.

Arterioscler Thromb Vasc Biol

. 1998;18:185-192. 5. Hirsch AT, et al.

JAMA

. 2001;286:1317-1324.

Prevalence of PAD Increases With Age

Rotterdam Study (ABI <0.9) 1 60 50 40 30 20 10 0 55-59 60-64 65-69 San Diego Study (PAD by noninvasive tests) 2 70-74 Age (years) 75-79 80-84 85-89

ABI=ankle-brachial index 1. Meijer WT, et al.

Arterioscler Thromb Vasc Biol

. 1998;18:185-192. 2. Criqui MH, et al.

Circulation

. 1985;71:510-515.

18 16 2 0 6 4 14 12 10 8 <70

Gender Differences in the Prevalence of PAD

6880 Consecutive Patients (61% Female) in 344 Primary Care Offices Women Men 70–74 75–79 Age (years) 80–84 >85

Adapted from Diehm C.

Atherosclerosis

. 2004;172:95-105 with permission from Elsevier.

10 9 8 7 6 5 4 3 2 1 0

Ethnicity and PAD:

The San Diego Population Study

NHW Black Hispanic Asian

NHW = Non-hispanic white.

Reprinted with permission from Criqui, et al.

Circulation.

2005:112:2703-07.

Diabetes Increases the Risk of PAD

25 20 15 10 5 0 12.5

19.9* Normal Glucose Tolerance Impaired Glucose Tolerance

Impaired glucose tolerance was defined as oral glucose tolerance test value ≥140 mg/dL but <200 mg/dL.

*P

 .05 vs. normal glucose tolerance. Reprinted with permission from Lee AJ, et al.

Br J Haematol.

1999;105:648-654. www.blackwell-synergy.com

22.4* Diabetes

CRP as Predictor of Incident PAD

0.2

0.17

0.13

0.1

0.1

0.0

None

CRP = C-reactive protein; hs-CRP = high-sensitivity C-reactive protein

Intermittent Claudication Peripheral Artery Surgery

Ridker, et al.

Circulation.

1998;97:425-28.

Risk Factors for PAD

Reduced Increased

Smoking Diabetes Hypertension Hypercholesterolemia Hyperhomocysteinemia C-Reactive Protein Relative Risk 0 1 2 3 4 5 6 Hirsch AT, et al.

J Am Coll Cardiol.

2006;47:e1-e192.

PARTNERS: Prevalence of PAD and Other CVD in Primary Care Practices

29% of Patients in a Target Population Were Diagnosed With PAD Using An Office-Based ABI ABI=ankle-brachial index; CVD=cardiovascular disease.

29% 44% 56%

Patients diagnosed with PAD PAD only PAD and CVD Hirsch, AT et al.

JAMA

. 2001;286:1317-24.

Individuals “At Risk” for Lower Extremity PAD

Based on the epidemiologic evidence base, an “at risk” population for PAD can be objectively defined by:

• • • • • • Age less than 50 years with diabetes, and one additional risk factor (e.g., smoking, dyslipidemia, hypertension, or hyperhomocysteinemia) Age 50 to 69 years and history of smoking or diabetes Age 70 years and older Leg symptoms with exertion (suggestive of claudication) or ischemic rest pain Abnormal lower extremity pulse examination Known atherosclerotic coronary, carotid, or renal artery disease

PAD Prognosis

The Natural History of PAD

• Individuals with PAD are at increased risk for cardiovascular ischemic events due to concomitant CAD (fatal and non-fatal MI) and cerebrovascular disease (fatal and non-fatal stroke).

• Cardiovascular events are more frequent than ischemic limb events in any lower extremity PAD cohort, regardless of the clinical presentation.

Natural History of Atherosclerotic Lower Extremity PAD

PAD Population (50 years and older) Initial clinical presentation Asymptomatic PAD 20%-50% Atypical leg pain 40%-50% Claudication 10%-35% Critical limb ischemia 1%-2% 1-year outcomes Progressive functional impairment Alive w/ 2 limbs 50% 5-year outcomes

(to next slide)

Amputation 25% CV mortality 25% Reprinted with permission from Hirsch AT, et al.

Circulation.

2006;113:e463-654.

Natural History of Atherosclerotic Lower Extremity PAD

For each of these PAD clinical syndromes Asymptomatic PAD 20%-50% Claudication 10%-35% 5-year outcomes Atypical leg pain 40%-50% Limb morbidity CV morbidity & mortality Stable claudication 70%-80% Worsening claudication 10%-20% Critical limb ischemia 1%-2% Amputation (see CLI data) Nonfatal CV event (MI or stroke) 20% Mortality 15%-30% CV causes 75% Non-CV causes 25% CLI=critical limb ischemia; CV=cardiovascular; MI=myocardial infarction Reprinted with permission from Hirsch AT, et al.

Circulation.

2006;113:e463-654.

Contemporary PAD

Rates of Myocardial Infarction and Death

3649 subjects (average age 64 years) followed up for 7.2 years

Hooi JD, et al.

J Clin Epid.

2004;57:294 –300.

Long-Term Survival in Patients With PAD

100 75 50 25 Normal subjects Asymptomatic PAD Symptomatic PAD Severe symptomatic PAD 0 2 4 6

Year

8 10 12

Criqui MH et al.

N Engl J Med.

1992;326:381 386. Copyright © 1992 Massachusetts Medical Society. All rights reserved.

Relative Risk of Death in Patients With PAD

10 2 0 8 6 4 3.1

(1.9–4.9) 5.9

(3.0–6.6) 6.6

(2.9–14.9) All Causes CVD

Cause of Death

CHD

CI=confidence interval; CHD=coronary heart disease; CVD=cardiovascular disease.

Criqui MH, et al.

N Engl J Med.

1992;326:381-386.

10-Year Natural History in Patients With Intermittent Claudication

100 80 60 40 20 0 0 Survival MI Intervention Amputation 1 2 3 4 5 6

Time (years)

7 8 9 10

Ouriel K.

Lancet.

2001;358;1257-1264.

Association Between ABI and All-Cause Mortality*

80 70 60 50 40 30 20 10 0

Risk increases at ABI values below 1.0 and above 1.3

N=5748 <0.61

(n=156) 0.61-0.70

(n=141) 0.71-0.80

(n=186) 0.81-0.90

(n=310) 0.91-1.00

(n=709) 1.01-1.10

(n=1750) 1.11-1.20

(n=1578) 1.21-1.30

(n=696) 1.31-1.40

(n=156)

Baseline ABI

>1.40

(n=66)

Age range=mid- to late-50s; ABI=ankle-brachial index; *Median duration of follow-up was 11.1 (0.1

–12) years.

Adapted from O’Hare AM et al.

Circulation

. 2006;113:388-393.

Cardiovascular Risk Increases With Decreases in Ankle-Brachial Index

4 3 2

Framingham “High Risk” = 20% at 10 years Every patient with PAD is at “very high risk”

5-year risk: 19% 3.8% 5-year risk: 10% 2% 1 1.4% 0 >1.1

1.1–1.01 1.0–0.91 0.9–0.71

ABI

PAD

<0.7

Leng GC, et al.

Brit Med J.

1996;313:1440-44.

*Fatal or nonfatal MI. ABI=ankle-brachial index; CHD=chronic heart failure

Baseline Physical Activity and Mortality in Persons With PAD

10 P = 0.02

P-trend = 0.003

P = 0.07

8 6 4 2 0 P = 0.61

1st Quartile 2nd Quartile 3rd Quartile Physical Activity Quartile 4th Quartile Reprinted with permission from Garg P K, et al.

Circulation.

2006;114:242-248.

Mortality According to ABI and Diabetes:

Strong Heart Study

n=4393 80 70 60 50 40 30 20 10 0 Nondiabetic IFG Diabetic <0.90

0.91 to 1.40 >1.4

Ankle-Brachial Index Reprinted with permission from Resnick, H. E. et al.

Circulation.

2004;109:733-739.

ABI=ankle-brachial index

;

IFG=impaired fasting glucose.

Critical Limb Ischemia (CLI)

Fate of Patients With CLI After Initial Treatment Summary of 6-month outcomes from 19 studies Alive with amputation 35% Dead 20% Alive without amputation 45% Critical limb ischemia is defined as ischemic rest pain, nonhealing wounds, or gangrene.

Dormandy JA, Rutherford RB.

J Vasc Surg

. 2000;31:S1-S296.