Peripheral Arterial Disease

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Peripheral Arterial Disease

• Physicians Awareness Program

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(No Transcript)
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Objectives

• Increase the awareness of physicians (general
  practitioners, internists, cardiologists, and
  vascular surgeons) in Saudi Arabia about PAD
• Educate physicians about the importance of risk
  reduction therapies, in order to close the care,
  knowledge and action gaps.

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Agenda

• Part I Overview of Disease
• Atherothrombosis
• Epidemiology
• Management
• Part II Guidelines
• CV Risk Factor Reduction
• ( AHA/ACC, TASC II)

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Part I Overview of Disease
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What is Atherosclerosis?

• Clogging, narrowing, and hardening of large and
  medium-sized arteries

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What are the risk factors for Atherosclerosis?
Non-Modifiable Risk Factors Male gender
Advanced age Family history
Modifiable Risk Factors Major
Smoking Hypertension Diabetes
Hyperlipidemia
Minor Homocystenemia Obesity
Hypercoaguable state Physical inactivity
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Pathophysiology of Atherothrombosis
Thrombus Formation
Atherosclerosis

Rupture of Fibrous Cap
Erosion of Endothelium
Erosion of Calcium Nodule
Intraplaque Hemorrhage
Atherosclerosis leads to any number of four
possible types of thrombus formation

• Munger MA et al. J Am Pharm Assoc. 200444(suppl
  1)S5-S13.
• Libby P et al. Circulation. 20051113481-3488.

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Clinical Spectrum of Atherosclerosis

• Cerebrovascular disease
• Coronary artery disease
• Renal artery Diseases
• Visceral arterial disease
• Peripheral arterial disease
• Intermittent claudication
• Critical limb ischemia

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Atherothrombosis
Can Manifest in Multiple
Vascular Beds

• Atherothrombosis is a process that includes the
  following clinical consequences
• Ischemic stroke, MI, and PAD

• Patients with atherothrombosis have thrombus
  formations that can manifest in multiple vascular
  beds throughout the body

Munger MA et al. J Am Pharm Assoc. 200444(suppl
1)S5-S13.
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Atherothrombosis as a Cause of DeathBurden of
the disease
According to the World Health Organization in
2004 atherothrombosis was the leading cause of
death worldwidemore than AIDS and cancer
combined1,2
Mortality ()
Athero-thrombosis
InfectiousDisease
Cancer
Injuries
PulmonaryDisease
AIDS

• Only includes ischemic heart disease and
  cerebrovascular disease.
• Bakhai A. Pharmacoeconomics. 200422(suppl
  4)11-18.
• World Health Organization Report 2004. Available
  at http//www.who.org. Accessed January 29, 2007.

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Lets Talk about PAD
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How do patients with PAD present?
Symptomatic

• Intermittent claudication

• Critical Limb Ischemia
• Pain at rest
• Tissue loss
• Gangrene

Asymptomatic
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How do patients with PAD present?
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How do patients with PAD present?
Symptomatic 10
Asymptomatic 90
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Ankle Brachial Index
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Calculating the Ankle-Brachial Index
Right leg ABI
Left leg ABI
ABI Interpretation 0.90 is diagnostic of
peripheral arterial disease
Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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Role of ABI in PAD

• Confirms the diagnosis of PAD
• Detects significant PAD in (sedentary)
  asymptomatic patients
• Used in the differential diagnosis of leg
  symptoms to identify a vascular etiology
• Identifies patients with reduced limb function
  (inability to walk defined distances or at usual
  walking speed)
• Provides key information on long-term prognosis
• A 36-fold increased risk of CV mortality with an
  ABI lt0.90
• Provides further risk stratification
• A lower ABI indicating worse prognosis
• A Framingham risk score between 1020
• Highly associated with coronary and cerebral
  artery disease

Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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Epidemiology of PAD
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Prevalence of PAD
US Data
European Data
Saudi Data
Diehm2 Age 65
PARTNERS5 Age gt70, or between 5069 with history
of diabetes or smoking
San Diego4 Mean Age66
NHANES3 Age 70
NHANES3 Age gt40
Rotterdam1 Age gt55
Pilot Study6 Age gt45

• Prevalence was estimated using different methods
• Meijer WT et al. Arterioscler Thromb Vasc Biol.
  199818185-192.
• Diehm C et al. Atherosclerosis. 200417295-105.
• 3. Selvin E et al. NHANES. Circulation.
  2004110738-743.
• 4. Criqui MH et al. Circulation. 198571510-515.
• 5. Hirsch AT et al. JAMA. 20012861317-1324.

6. Alshaekh et al. SMJ. 200728412-414
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Why it is important to recognize patients
with PAD?
PAD is a marker of systemic atherosclerosis
Patients with either symptomatic or
asymptomatic PAD generally have widespread
arterial disease
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Peripheral Arterial Disease Prevalence of
Polyvascular disease
The REACH Registry found overlapping
manifestations of disease in patients with CAD,
CVD, and PAD
18.3 of patients in the REACH Registry did not
have manifestations of atherothrombosis, but
were included based on risk factors
sanofi-aventis and Bristol-Myers Squibb provide
funding for the REACH Registry. The REACH
Registry includes patients with conditions for
which clopidogrel may not be indicated. Bhatt DL
et al. JAMA. 2006295180-189.
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Long term Risk of MI Stroke
PAD places individuals at high short term risk
of MI, Stroke Death
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Survival of Patients With PAD
Life expectancy reduced 10 years in patients
with PAD Mortality rate 25 at 5 years 50
at 10 years 75 at 15 years
CLIcritical limb ischemia. ICintermittent
claudication. Norgren L et al. Eur J Vasc
Endovasc Surg. 200733(suppl 1)S1-S75.
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Natural History

• Annual risk
• - Mortality 6.8
• - MI 2.0
• - Intervention 1.0
• - Amputation 0.4

Ouriel K, Lancet 2001 358 1257-64.
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Major Adverse Cardiac Events in Symptomatic
Patients With CAD, CVD, or PAD at 1 Year
REACH Registry
Patients with PAD experienced high CV mortality
of Patients
sanofi-aventis and Bristol-Myers Squibb provide
funding for the REACH Registry. The REACH
Registry includes patients with conditions for
which clopidogrel may not be indicated. Rates
adjusted for age and risk factors. Steg G. Oral
presentation at American College of Cardiology.
2006. Available at http//acc06online.acc.org/ses
sions.aspx?date12. Accessed January 28, 2007.
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Major End Points as a Function of Single vs
Multiple and Overlapping Locations
REACH Registry
Risk doubles with polyvascular disease
Single Arterial Bed
Polyvascular Disease
CAD CVD PAD
CAD alone
Overall
PAD alone
Overall
CVD alone
1.2
1.5
1.5
2.4
1.4
CV death
3.6
1.5
1.0
0.5()
1.4
1.2
Non-fatal MI
1.8
3.1
0.6
3.5()
0.9
1.5
Non-fatal stroke
4.0
6.0
2.3
4.5()
3.1
3.4
CV death / MI/ stroke
7.4
22.0
18.2()
10.0()
13.3
12.8
CV death / MI/ stroke/ hospitalization
26.9()
Plt0.001 (ref class CAD alone) Plt0.001 (ref
class CAD CVD) Plt0.001 (ref class PAD alone)
sanofi-aventis and Bristol-Myers Squibb
provide funding for the REACH Registry. The
REACH Registry includes patients with conditions
for which clopidogrel may not be
indicated. TIA, unstable angina, other ischemic
arterial event including worsening of peripheral
arterial disease. Steg G. Oral presentation at
American College of Cardiology. 2006. Available
at http//acc06online.acc.org/sessions.aspx?date
12. Accessed January 28, 2007.
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Relationship Between ABI and Fatal and Non-fatal
CV events
The lower the ABI the higher the 5-year risk of a
cardiovascular event
Mehler PS et al. Circulation. 2003107753-756.
Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75
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All Cause Mortality as a Function of Baseline ABI
There appears to be an inverse correlation
between mortality and ABI

• PAD patients with an ABI 0.90 are at increased
  risk for cardiovascular events and all cause
  mortality as ABI decreases
• Patients with an ABI gt1.40 have underlying
  diseases, such as diabetes, renal insufficiency
  or other diseases that cause vascular
  calcification, or the tibial vessels at the ankle
  to become non-compressible

Resnick HE et al. Circulation. 2004109733e739. N
orgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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Management of PAD
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What are the Goals of treating patients with PAD?
Relief symptoms
Improve quality of life
Limb salvage
Prolong survival
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Strategies in treating patients with PAD
Improve Lower Limb Circulation
Risk Factors Modification
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Strategies in treating patients with PAD

• Improve Lower Limb Circulation
• Conservative (Exercise Program)
• Intervention ( Revascularization)
• - Angioplasty /- Stenting
• - Surgical Bypass

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Strategies in treating patients with PAD

• Risk Factors Modification
• Diet and weight control
• Exercise
• Antiplatlets
• Hypertension control
• Diabetes control
• Lipid control
• Smoking Cessation

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Part II Guidelines for Risk Factors Modification
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AHA/ACC
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AHA/ACC format
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Weight Management
Goal Body mass index 18.5 to 24.9 kg/m² Waist
circumference men lt40 inches
women lt 35 inches
Encourage weight reduction/maintenance Balance
of physical activity, caloric intake, and formal
behavioral programs
Adapted from ACC/AHA Guidelines for the
Management of Patients With Peripheral Arterial
Disease. J Am Coll Cardiol. 2006.
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Physical Activity
Goal 30 minutes, 7 days per week (minimum 5
days/week)
Moderate-intensity aerobic activity Medically
supervised programs for high risk
Adapted from ACC/AHA Guidelines for the
Management of Patients With Peripheral Arterial
Disease. J Am Coll Cardiol. 2006.
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Smoking
Goal Complete Cessation
Ask about smoking Advise to quit Counseling Refera
l to special program Pharmacotherapy
Adapted from ACC/AHA Guidelines for the
Management of Patients With Peripheral Arterial
Disease. J Am Coll Cardiol. 2006.
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Pharmacologic Risk Reduction Strategies
ASA and other anti-platelet agents
Hypertension Control
Lipid Control
Diabetes Control
Angiotensin Converting Enzyme Inhibitors (ACE-I)
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Antiplatelet Therapy

• The Antithrombotic Trialists Collaboration
  involved 42 trials and 9716 patients with
  peripheral arterial disease.
• 23 reduction for adverse cardiovascular events,
  including myocardial infarction, stroke, or
  vascular death

Antiplatelet therapy is indicated to reduce the
risk of myocardial infarction, stroke, or
vascular death in individuals with
atherosclerotic lower extremity PAD.
Adapted from ACC/AHA Guidelines for the
Management of Patients With Peripheral Arterial
Disease. J Am Coll Cardiol. 2006.
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Efficacy of Clopidogrel vs Aspirin in MI,
Ischemic Stroke, or Vascular Death (N19,185)1
CAPRIE
Median Follow-up1.91 years
8.7
Aspirin
Overall Relative RiskReduction2
16
Clopidogrel
12
Aspirin
Cumulative Event Rate ()
P0.0452
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Clopidogrel
Study subjects had either recent MI, recent
ischemic stroke, or established peripheral
arterial disease.
4
0
0
3
6
9
12
15
18
21
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Months of Follow-Up

• ITT analysis.
• CAPRIE Steering Committee. Lancet.
  19963481329-1339.
• Clopidogrel Prescribing Information.

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Outcomes by Subgroup Analysis
CAPRIE
Aspirin Better
Clopidogrel Better
CAPRIE primary combined end point (myocardial
infarction, ischemic stroke, vascular death) RRR
8.7 (P0.045) for patients with PAD,
post-myocardial infarction, post-ischemic stroke.
CAPRIE subgroup analysis for PAD patients the
secondary end point, myocardial infarction, was
reduced by 23.8 (RRR). Since the CAPRIE Trial
was not powered to evaluate the efficacy of
individual sub-groups, it is not clear whether
the differences in RRR across qualifying
conditions are real or a result of chance.
CAPRIE Steering Committee. Lancet.
19963481329-1339.
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Antihypertensive Therapy
Antihypertensive therapy should be administered
to hypertensive patients with lower extremity PAD
to a goal of less than 140/90 mmHg
(non-diabetics) or less than 130/80 mm/Hg
(diabetics and individuals with chronic renal
disease) to reduce the risk of myocardial
infarction, stroke, congestive heart failure, and
cardiovascular death.
Adapted from ACC/AHA Guidelines for the
Management of Patients With Peripheral Arterial
Disease. J Am Coll Cardiol. 2006.
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Lipid Lowering Therapy

• Cholesterol Treatment Trialists Coolaborators
  Meta-analysis data from 90 056 participants in 14
  randomized trials of statins
• 21 reduction for adverse cardiovascular events,
  including myocardial infarction, stroke, or
  vascular death
• (Lancet 2005 3661267-78)

Treatment with an HMG coenzyme-A reductase
inhibitor (statin) medication is indicated for
all patients with peripheral arterial disease to
achieve a target LDL cholesterol of less than 100
mg/dl.
Adapted from ACC/AHA Guidelines for the
Management of Patients With Peripheral Arterial
Disease. J Am Coll Cardiol. 2006.
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Diabetes Therapies
Treatment of diabetes in individuals with lower
extremity PAD by administration of glucose
control therapies to reduce the hemoglobin A1C to
less than 7 can be effective to reduce
microvascular complications and potentially
improve cardiovascular outcomes.
Adapted from ACC/AHA Guidelines for the
Management of Patients With Peripheral Arterial
Disease. J Am Coll Cardiol. 2006.
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ACE inhibitors

• The HOPE study involved 9297 AS patients.
• 25 reduction for adverse cardiovascular events,
  including myocardial infarction, stroke, or
  vascular death

ACE inhibitors is indicated to reduce the risk
of myocardial infarction, stroke, or vascular
death in individuals with atherosclerotic lower
extremity PAD.
B
Adapted from ACC/AHA Guidelines for the
Management of Patients With Peripheral Arterial
Disease. J Am Coll Cardiol. 2006.
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TASC II
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Goals of TASC II

• Update and expand the consensus statement from
  2000
• Maintain focus on peripheral arterial disease
• Make the document accessible to a wider audience
• Including primary care physicians
• Reduce the length of the document
• Inclusion of Europe, North America, Asia, Africa,
  Australia

Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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TASC II Participating Societies

• American College of Cardiology
• American Diabetes Association
• American Podiatric Medical Association
• Canadian Society for Vascular Surgeons
• Cardiovascular and Interventional Radiology
  Society of Europe
• CoCaLis collaboration
• European Society for Vascular Surgery
• International Diabetes Federation

• International Union of Angiology
• Interventional Radiology Society of Australasia
• Japanese College of Angiology
• Society for Cardiovascular Angiography and
  Intervention
• Society for Vascular Surgery
• Society of Interventional Radiology
• Society for Vascular Medicine Biology
• Vascular Society of Southern Africa

Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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TASC Grade Definition
TASC II
Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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PAD Patients Are at Increased Risk for CV
Ischemic Events
PAD Patients 50 Years and Older Initial
Presentation
The majority of PAD patients remain highly
underdiagnosed
Symptomatic 40 of Patients
Asymptomatic 60 of Patients
5-year Outcomes
Limb Morbidity 7080Stable claudication
1020Worsening claudication 510Critical
limb ischemia
Mortality 101575 from CV causes
CV Morbidity 20Nonfatal CV event (MI or
stroke)
Up to 35 of PAD patients will have an MI/stroke
or die in the next 5 years
Excluding patients with an initial presentation
of critical limb ischemia. Adapted from Hirsch
AT et al. Available at www.acc.org. Accessed
January 26, 2007. Adapted from Norgren L et al.
Eur J Vasc Endovasc Surg. 200733(suppl
1)S1-S75.
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History and Physical Examination in Patients
With Suspected PAD
Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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TASC II Guidelines Ankle Brachial Index (ABI)
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Ankle-Brachial Index (ABI)
TASC II

• The primary non-invasive screening test for PAD
  is the ankle-brachial index
• The American Diabetes Association recommends a
  screening with an ABI every 5 years in patients
  with diabetes
• The ABI should become a routine measurement in
  the primary care practice of medicine

Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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Ankle-Brachial Index (ABI)- Screening
Recommendations
TASC II
Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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ABI for Assessing Systemic Risk
TASC II
Cardiovascular 10-year risk score
Highgt20
Lowlt10
Moderate2010
ABI
Secondary prevention
0.90
gt0.90
Primary prevention

• Evaluate the patient for symptoms of PAD
• Manage claudicationand CLI if present

Primary preventionNo antiplatelet therapy LDL
(low density lipoprotein) lt130 mg/dL appropriate
blood pressure (lt140/90 mmHg and lt130/80 mmHg in
diabetes/renal insufficiency). Secondary
preventionPrescribe antiplatelet therapy LDL
lt100 mg/dL (lt70 mg/dL in very high risk)
appropriate blood pressure (lt140/90 mmHg and
lt130/80 mmHg in diabetes/renal insufficiency). No
rgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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TASC-II Guidelines for Risk Reduction
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TASC Guidelines Recommend CV Risk Reduction and
Symptom Relief
Evidence Basis for Selected Treatment
Recommendations
To improve symptoms and increase walking
distance. Norgren L et al. Eur J Vasc Endovasc
Surg. 200733(suppl 1)S1-S75
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Antiplatelet Therapy
Norgren L et al. Eur J Vasc Endovasc Surg.
200733(suppl 1)S1-S75.
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So, Lets wrap-up
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Who should be screened for PAD?
Age gt 45 years
Patients with Atherosclerotic risk factors
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What is the best way to screen?
ABI
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Summary of the Evidence
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Summary of the Evidence
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Take home message

• PAD is a marker for systemic atherosclerosis
• PAD is associated with increased risk of
  cardiovascular mortality and morbidity
• Majority of patients with PAD are asymptomatic
• Individuals with atherosclerotic risk factors
  should be screened for PAD (ABI measurement)
• Proven risk reduction therapy should be
  prescribed for patients with PAD

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Thank You