diffuse vascular disease (focus on peripheral arterial disease [pad])

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Diffuse Vascular Disease Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD]) (Focus on Peripheral Arterial Disease [PAD]) Case Study: Diane Leary Case Study: Diane Leary

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Case Study: Diane Leary. Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD]). Learning Objectives. At the end of this session, participants should be able to: Identify patients with peripheral arterial disease (PAD) - PowerPoint PPT Presentation

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Page 1: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Diffuse Vascular DiseaseDiffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])(Focus on Peripheral Arterial Disease [PAD])

Case Study: Diane LearyCase Study: Diane Leary

Page 2: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Learning ObjectivesLearning Objectives

At the end of this session, participants should be able to:

Identify patients with peripheral arterial disease (PAD)

Apply Canadian guidelines for the screening and management of PAD

Identify patients with diffuse vascular disease and implement strategies for the prevention of atherothrombotic events in these patients

Page 3: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Patient PresentationPatient Presentation

▪ Diane is a 65-year-old retired school teacher

▪ She complains of left calf pain when walking a couple of blocks; the pain goes away after she rests for 5 minutes

▪ No other complaints

Page 4: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

HistoryHistory

▪ NSTEMI 20 months ago

▪ Carotid bruit

▪ Hypertension

▪ Type 2 diabetes (diagnosed 5 years prior)

▪ Hyperlipidemia

▪ No family history of diabetes or cardiovascular disease

▪ Former smoker

NSTEMI: non-ST-elevation myocardial infarction

Page 5: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

MedicationsMedications

▪ ASA 81 mg/day

▪ Ramipril 10 mg/day

▪ Metformin 500 mg tid

▪ Atorvastatin 20 mg/day

▪ Metoprolol 25 mg bid

ASA: acetylsalicylic acid

Page 6: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Physical ExaminationPhysical Examination

▪ Height: 1.65 m

▪ Weight: 81.6 kg

▪ BMI: 29 kg/m2

▪ Waist circumference: 104 cm

▪ BP in-office: 128/72 mmHg

▪ Heart rate: 80 bpm

▪ Left femoral bruit

▪ Carotid bruit

▪ Bilateral reduced pedal pulsesBMI: body mass index; BP: blood pressure

Page 7: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Laboratory InvestigationsLaboratory Investigations

▪ FPG: 6.2 mmol/L

▪ A1C: 7.5%

▪ Lipids at desired values– TC < 5.2 mmol/L

– TG < 2.3 mmol/L

– HDL-C > 1.20 mmol/L (female)

– LDL-C < 2.0 mmol/L

– TC/HDL-C < 4.0

▪ Urine ACR: 1.9 mg/mmol

▪ Complete blood count within normal limits

▪ ECG normal

FPG: fasting plasma glucose; A1C: hemoglobin A1C; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; ACR: albumin-to-creatinine ratio; ECG: electrocardiogram

Page 8: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Question 1Question 1

What is your initial diagnosis?

Page 9: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Key PointsKey Points

▪ Patient presents with typical symptom of PAD (intermittent claudication) and has a number of risk factors for the disease

▪ Basic screening should include directed history and physical exam focusing on femoral bruits and pedal pulses

▪ Non-invasive evaluation should include an ABI

ABI: ankle-brachial index

Page 10: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Risk Factors for PADRisk Factors for PAD

Teo KK. Can J Cardiol. 2005;21(12):997–1006.

• Risk factors for PAD are similar to those for atherosclerosis in other beds and include:

• Smoking and diabetes are the most predictive for development of symptomatic claudication

Non-Modifiable Modifiable

▪ Age▪ Male sex▪ Family history

▪ Elevated lipid levels▪ Cigarette smoking▪ Hypertension▪ Sedentary lifestyle▪ Obesity▪ Diabetes

Page 11: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Varied Presentation of PADVaried Presentation of PAD

PAD can be silent or cause symptoms ranging PAD can be silent or cause symptoms ranging from pain to critical limb ischemiafrom pain to critical limb ischemia

Typical AtypicalIntermittent claudication: pain, ache, cramp, numbness, muscle fatigue in calves, thighs or buttocks; exacerbated by exercise and relieved by rest

Decreased walking ability: (speed or distance) for reasons other than classical symptoms of intermittent claudication

Critical limb ischemia: rest pain, ulcers, gangrene

Pain in other areas: e.g., general aching

McDermott MM et al. JAMA 2001;286:1599-1606.

Page 12: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

CVD

16.6%CAD

44.6%8.4%

1.2%4.7%

1.6%

PAD

4.7%

REACH RegistryREACH RegistryAtherothrombosis: Overlapping Manifestations of DiseaseAtherothrombosis: Overlapping Manifestations of Disease

The REACH Registry found overlapping manifestations of disease in patients with CAD, CVD, and PAD

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

18.3% of patients in the REACH Registry did not have manifestations of atherothrombosis, but were included based on risk factors

▪ 61% of PAD patients also had symptomatic disease in the coronary or cerebral circulation

▪ 40% of CVD patients also had symptomatic disease in the coronary or peripheral circulation

▪ 25% of CAD patients also had symptomatic disease in the cerebral or peripheral circulation

Bhatt DL, et al; for the REACH Registry Investigators. JAMA. 2006;295:180-189.

CAD: coronary artery disease; CVD: cerebrovascular disease; PAD: peripheral arterial disease

Page 13: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Increased Risk of PAD with DiabetesIncreased Risk of PAD with Diabetes

12.5

19.922.4

0

5

10

15

20

25

**

*

Normal glucosetolerance

Impaired glucosetolerance

Diabetes

Pre

vale

nce

of

PA

D (

%)

Impaired glucose tolerance was defined as oral glucose tolerance test value ≥140 mg/dL <200 mg/dL.* P≤0.05 vs. normal glucose tolerance.

Lee AJ, et al. Br J Haematol. 1999;105:648–654.

Page 14: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Question 2Question 2

What additional investigations would you perform?

Page 15: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Key Points: Diagnosis of PADKey Points: Diagnosis of PAD

History Edinburgh Questionnaire

Physical examination Bruit Peripheral pulses

Non-invasive tests ABI Arterial Duplex

Adapted from Roussin A, et al. Can J Cardiol. 2005;21(12):997–1006.

Page 16: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

CCS Guidelines: Diagnosis of PADCCS Guidelines: Diagnosis of PAD

Roussin A, et al. Can J Cardiol. 2005;21(12):997–1006.

Recommendation Grade

Taking a directed history for symptoms of PAD. A validated questionnaire, such as the Edinburgh Questionnaire, can help diagnose arterial claudication in patients suspected of suffering from PAD.

1A

Performing a directed examination focusing on physical findings that have been proven useful to detect PAD defined as an ABI<0.9.

1A

Ordering an ABI to help diagnose arterial claudication in patients suspected of claudication. An ABI below 0.9 is diagnostic PAD with values below 0.4 associated with severe disease.

1A

Ordering an ABI to diagnose PAD in asymptomatic patients with arterial bruits or diminished pulses.

1A

Page 17: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Edinburgh Questionnaire

Do you get a pain or discomfort in your leg(s) when you walk?• YES (If patient answers no, then stop here)

Does this pain ever begin when you are standing still or sitting?• NO

Do you get it when you walk uphill or hurry?• YES

Do you get it when you walk at an ordinary pace on level ground?• YES (Answer may also be ‘no’ depending on severity of claudication)

What happens to it if you stand still?• Pain usually disappears in 10 minutes or less (pain continuing for more than 10 minutes is not consistent with PAD)

Where do you get this pain or discomfort?• Patient marks calf and/or thigh and/or buttock

(A positive diagnosis of PAD requires the responses indicated in yellow for all questions)

Leng GC, et al. J Clin Epidemiol. 1992;45:1101–1109.

Page 18: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Measuring ABI

Adapted from Roussin A, et al. Can J Cardiol 2005;21(12):997-1006.

RIGHT ABI

LEFT ABI

INTERPRETATION OF ABI

Right-armsystolicpressure

Left-armsystolicpressure

Right-anklesystolic pressure

Left-anklesystolic pressure

DP

PT

DP

PT

>1.30

0.91-1.30

0.41-0.90

0.00-0.40

Noncompressible

Normal

Mild-to-moderate peripheral arterial disease

Severe peripheral arterial disease

Higher right-ankle pressure

Higher arm pressure

Higher left-ankle pressure

Higher arm pressure

Page 19: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Question 3Question 3

What if the patient’s pedal pulses were palpable and there were no bruits? Would this change your diagnosis?

Page 20: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Key PointKey Point

▪ Palpable pedal pulses and an absence of femoral bruits do not preclude PAD

Page 21: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

PAD Regardless of ClaudicationPAD Regardless of Claudication

• Value of physical examination relative to presence of PAD

McGee SR, et al. Arch Intern Med. 1998;158:1357–1364.

ITEM Sensitivity Specificity RR if present

Reduced pedal pulses 68% 95% 27

Femoral bruit 29% 95% 5.7

Slow venous filling 23% 95% 4.1

Cold skin 10% 98% 5.8

Abnormal colour 35% 87% 2.8

Trophic changes 46% 46% 1.5

Page 22: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Case EvolutionCase Evolution

▪ Based on your clinical examination, you diagnose Diane with PAD. You perform further investigations and find that she has an ABI of 0.65, which confirms your diagnosis.

Significance of ABI values ►

Page 23: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Question 4Question 4

How would you manage this patient’s:a) claudication?b) overall vascular risk?

Page 24: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Key Points: Key Points: Objectives of PAD TherapyObjectives of PAD Therapy

Prevent death and disability

Reduce risk of MI (PAD quadruples MI risk)

Reduce risk of stroke (PAD triples stroke risk)

Relieve symptoms

Improve QOL

Improve walking ability

Save limbs

Prevent major amputations

Avoid tissue loss QOL: quality of life

Page 25: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Survival Following Diagnosis of PAD Survival Following Diagnosis of PAD by Diabetes Statusby Diabetes Status

Migliaccio-Walle K, et al. Can J Diabetes. 2007;31(2):140-147.

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

10

20

30

40

50

60

70

80

90

100

Pro

po

rtio

n a

live

(%

)

Time (years)

Diabetes

No diabetes

Page 26: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

CCS Guidelines for PAD: CCS Guidelines for PAD: Risk Reduction StrategiesRisk Reduction Strategies

Anand SS, et al. Can J Cardiol. 2005;21(12):997–1006.

Non-pharmacologic Pharmacologic

• Exercise• Blood pressure control• Lipid control• Habits

- Smoking

• Antiplatelet therapy• Angiotensin converting enzyme

inhibitors (ACE-I)• Diabetes control• Hypertension control• Statin use

Page 27: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Risk Factor ManagementRisk Factor Management

Smoking cessation

Weight reduction

Regular physical activity

LDL-C < 2.0 mmol/L

Glycosylated hemoglobin < 6.0%

BP < 140/90 mmHg; < 130/80 mmHg in patients with diabetes

Platelet inhibition

Hiatt WR. N Engl J Med. 2001;344:1608-1621.

McPherson R, et al. Can J Cardiol. 2006;22:913-927.

CDA 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Available at http://www.diabetes.ca/cpg2003

2007 CHEP Recommendations. Available at www.hypertensions.ca

Page 28: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Medical therapies to reduce cardiovascular events in PAD

CCS Guidelines for PAD: CCS Guidelines for PAD: Pharmacologic ApproachPharmacologic Approach

Anand SS, et al. Can J Cardiol. 2005;21(12):997–1006.

CLASS OF AGENTS GRADE

Statins 1A

ACE inhibitors 1A

Oral hypoglycemics or insulin 2B

Antiplatelet 1A

Page 29: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

CCS Guidelines:CCS Guidelines:Antithrombotic TherapiesAntithrombotic Therapies

Anand SS, et al. Can J Cardiol. 2005;21(12):997–1006.

AGENTS RECOMMENDATION GRADE

ASA or Clopidogrel

Lifelong antiplatelet therapy with ASA (75 to 325 mg/day) or clopidogrel (75 mg/day) in patient with or without clinically manifest coronary or cerebrovascular disease.

1A

Ticlopidine ASA or clopidogrel recommended over ticlopidine. 1B

Cilostazol* Recommendation for patients with disabling intermittent claudication who do not respond to conservative measure (risk factor modification and exercise therapy) and who are not candidates for surgical or catheter-based intervention

1B

Pentoxifylline Pentoxifylline is not recommended 2B

Vitamin K Antagonists

Anticoagulant therapy is not recommended 2B

*Not available in Canada

Page 30: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Supervised Exercise in the Supervised Exercise in the Management of Symptomatic PADManagement of Symptomatic PAD

Exercise prescription is fundamental for all patients with claudication

Supervised programs have patients walk to the point of moderate pain, followed by rest and repeat exercise

Benefit is observed as early as 4 weeks and continues to improve for at least 1 year

Anand SS, Turpie AGG, et al. Can J Cardiol. 2005;21(12):997–1006.

Page 31: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Question 5Question 5

Could warfarin be added to antiplatelet therapy in patients with PAD?

Page 32: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

WAVE: WAVE: Warfarin Antiplatelet Vascular EvaluationWarfarin Antiplatelet Vascular Evaluation

COMBINATIONn=1080 (%)

ANTIPLATELETONLY

n=1081 (%)

RELATIVE RISK

(95% CI) P

MI, stroke, or CV death 12.2 13.3 0.92 (0.73 - 1.16)

0.48

MI, stroke, CV death, or severe CAD– or PAD-related ischemia

15.9 17.4 0.91 (0.74 - 1.12)

0.37

Ischemic stroke 2.2 3.5 0.64 (0.38 - 1.06)

0.09

Hemorrhagic stroke 1.3 0 15.2 (2.0 - 115.6)

0.001

Life-threatening bleeding 4.0 1.2 3.41 (1.84 - 6.35)

<0.001

Moderate bleeding 2.9 1.0 2.82 (1.43 - 5.58)

0.002

Minor bleeding 38.6 10.6 3.63 (3.01 - 4.38)

<0.001

WAVE Trial Investigators. N Engl J Med. 2007;357(3):217-27.

Page 33: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Question 6Question 6

Given this patient’s history of ACS and current diagnosis of PAD (ie, diffuse vascular disease), how long should she remain on the prescribed antiplatelet regimen?

Review pathophysiology & epidemiology of polyvascular disease and atherothrombosis ►

Page 34: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Key PointsKey Points

▪ High risk of CV death, MI, stroke or hospitalization in patients with diffuse vascular disease1

▪ Aggressive risk reduction strategies and dual antiplatelet therapy should be considered for these patients

▪ Currently no guideline recommendations on the optimal duration of antiplatelet therapy in patients with diffuse vascular disease; however, many experts would agree that this patient requires lifelong antiplatelet therapy

– CCS recommends lifelong antiplatelet therapy in PAD2

– CHARISMA showed that patients with a prior atherothrombotic event (MI, stroke or PAD) benefit from long-term dual antiplatelet therapy (median follow-up 27 months), but at the cost of an increased rate of bleeding3

1. Steg PG, et al.; for the REACH Registry Investigators. JAMA. 2007;297:1197-206. 2. Abramson BL, et al. Can J Cardiol. 2005;21(12):997–1006. 3. Bhatt DL, et al.; CHARISMA Investigators. J Am Coll Cardiol. 2007;49(19):1982-8.

CHARISMA: Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance

Page 35: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

REACHREACHMajor endpoints as a Function of Single vs Major endpoints as a Function of Single vs Multiple and Overlapping LocationsMultiple and Overlapping Locations

Single Arterial Bed Polyvascular Disease

Overall CAD alone

CVD alone

PAD alone Overall CAD + CVD +

PAD

CV Death 1.5 1.5 1.4 1.2 2.4 3.6

Non-fatal MI 1.2 1.4 0.5† 1.0 1.5 1.8

Non-fatal stroke 1.5 0.9 3.5† 0.6 3.1 4.0

CV death/MI/stroke 3.4 3.1 4.5† 2.3 6.0 7.4

CV death/MI/stroke/ hospitalization*

12.8 13.3 10.0† 18.2§ 22.0 26.9‡

Risk doubles with diffuse vascular disease

† P<0.001 (ref class: CAD alone)§ P<0.001 (ref class: PAD alone)‡ P<0.001 (ref class: CAD + CVD)

Steg PG, et al.; for the REACH Registry Investigators. JAMA. 2007;297:1197-206.

Page 36: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

CCS Guidelines:CCS Guidelines:Antithrombotic TherapiesAntithrombotic Therapies

Anand SS, et al. Can J Cardiol. 2005;21(12):997–1006.

Agents Recommendation Grade

ASA or Clopidogrel

Lifelong antiplatelet therapy with ASA (75 to 325 mg/day) or clopidogrel (75 mg/day) in patient with or without clinically manifest coronary or cerebrovascular disease.

1A

Ticlopidine ASA or clopidogrel recommended over ticlopidine. 1B

Cilostazol Recommendation for patients with disabling intermittent claudication who do not respond to conservative measure (risk factor modification and exercise therapy) and who are not candidates for surgical or catheter-based intervention

1B

Pentoxifylline Pentoxifylline is not recommended 2B

Vitamin K Antagonists

Anticoagulant therapy is not recommended 2B

Page 37: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

CAPRIE:CAPRIE:Clopidogrel vs. ASA in Multi-bed DiseaseClopidogrel vs. ASA in Multi-bed Disease

15

5

0

An

nua

l eve

nt r

ate

(%

)

Clopidogrel ASA

Events = ischemic stroke, MI or vascular death

CAPRIE Steering Committee. Lancet. 1996;348(9038):1329-39.

108.35%

10.74%

164 events 196 events

22.7%

Relative RiskReduction

Page 38: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

CHARISMA:CHARISMA:Primary Endpoint (MI/Stroke/CV Death) in Patients with Primary Endpoint (MI/Stroke/CV Death) in Patients with Previous MI, IS, or PADPrevious MI, IS, or PAD

RRR: 17.1 % [95% CI: 4.4%, 28.1%]P=0.01

Pri

mar

y o

utc

om

e ev

ent

rate

(%

)

0

2

4

6

8

10

Months since randomization

0 6 12 18 24 30

Clopidogrel + ASA7.3 %

Placebo + ASA8.8 %

N=9,478

““CAPRIE-like Cohort”CAPRIE-like Cohort”

Bhatt DL, et al.; CHARISMA Investigators. J Am Coll Cardiol. 2007;49(19):1982-1988.

Page 39: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

CHARISMA:CHARISMA:Primary and Secondary Safety EndpointsPrimary and Secondary Safety Endpoints

Endpoint, n (%)Clopidogrel +

ASA

(n=4735)

Placebo + ASA

(n=4743)

HR (95% CI)

P Value

Severe bleeding 79 (1.7) 71 (1.5) 1.114 (0.808–1.535) 0.509

Fatal bleeding 15 (0.3) 11 (0.2) 1.362 (0.626–2.966) 0.434

Primary intracranial hemorrhage 17 (0.4) 20 (0.4) 0.849 (0.445–1.621) 0.619

Moderate bleeding 97 (2.0) 61 (1.3) 1.597 (1.159–2.200) 0.004

Bhatt DL, et al.; CHARISMA Investigators. J Am Coll Cardiol. 2007;49(19):1982-1988.

Page 40: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

CHARISMA:CHARISMA:Timing of Severe or Moderate BleedingTiming of Severe or Moderate Bleeding

Placebo + ASA

Clopidogrel + ASA

Days Since Randomization

15 60 135 270 450 630 810

0.00008

0.00007

0.00006

0.00005

0.00004

0.00003

0.00002

0.00001

0

Haz

ard

Fu

nct

ion

/d

Bhatt DL, et al.; CHARISMA Investigators. J Am Coll Cardiol. 2007;49(19):1982-1988.

Page 41: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Take-Home MessagesTake-Home Messages

▪ Patients with PAD are at increased risk of diffuse vascular disease (ie, CAD and CVD)

▪ Screen for PAD through history (Edinburgh Questionnaire) and physical examination (femoral bruits and pedal pulses)

▪ Definitive diagnosis of PAD requires an ABI < 0.9

▪ Aggressive risk factor management should be considered for patients with diffuse vascular disease

▪ Long-term dual antiplatelet therapy can also be considered in selected cases but it is important to weigh the benefits against the higher risk of bleeding

Page 42: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

HYPERLINKSHYPERLINKS

Page 43: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Significance of ABI ValuesSignificance of ABI Values

Page 44: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

GetABI: GetABI: Mortality (All-cause) by ABI CategoryMortality (All-cause) by ABI Category

Diehm C. Presented at ESC Congress. Vienna, Austria. September 4, 2007.

> 1.1

0.9 – 1.1

0.7 – 0.9

0.5 – 0.7

< 0.5

Page 45: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

*Mean participant follow-up 8.3 years

Strong Association Between Decreased Strong Association Between Decreased ABI & Increased Risk for Vascular DeathABI & Increased Risk for Vascular Death

Baseline ABI*

Per

cen

t (%

)

0

20

40

60

<0.60 (n=25)

50

30

10

0.60-<0.70 (n

=21)

0.70-<0.80 (n

=40)

0.80-<0.90 (n

=130)

0.90-<1.0 (n

=195)

1.0-<1.10 (n

=980)

All-cause mortality

Vascular disease mortality

Resnick HE, et al. Circulation. 2004;109:733-739.RETURN

Page 46: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Pathophysiology, Epidemiology & BurdenPathophysiology, Epidemiology & Burdenof Atherothrombosisof Atherothrombosis

Page 47: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Pathophysiology of AtherothrombosisPathophysiology of Atherothrombosis

1. Munger MA et al. J Am Pharm Assoc. 2004;44(suppl 1):s5-s13.2. Libby P et al. Circulation. 2005;111:3481-3488.

AtherosclerosisAtherosclerosis +

Atherosclerosis leads to any number of four possible types of thrombus formation

InflammationAccumulationof lipids

Normalartery

Smooth muscle cell progression,

plaque progression

Thrombus FormationThrombus Formation

Rupture of Fibrous Cap

Erosion of Endothelium

Erosion of Calcium Nodule

Intraplaque Hemorrhage

Page 48: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

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

Atherothrombosis Can Manifest in Atherothrombosis Can Manifest in Multiple Vascular BedsMultiple Vascular Beds

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

Munger MA et al. J Am Pharm Assoc. 2004;44(suppl 1):s5-s13.

Page 49: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Cerebrovascular disease (CVD)

Peripheral Arterial Disease (PAD)

Coronary artery disease (CAD)

9%14%

13%

5%

Atherothrombosis: Disease Overlap

Patients with > 1 manifestation = 41%

Aronow WS, Ahn C. Am J Cardiol. 1994;74:64-65.

Page 50: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Epidemiology of Atherothrombotic Epidemiology of Atherothrombotic Manifestations in CanadaManifestations in Canada

Stroke1.0%1

Stroke1.0%1

MI2.7% (men)2

1.5% (women)2

MI2.7% (men)2

1.5% (women)2

PAD3.0%

(10.5 million†4

in North America)

PAD3.0%

(10.5 million†4

in North America)

Patients with a Patients with a history of history of

atherothrombosis atherothrombosis are most likely to are most likely to die of a recurrent die of a recurrent atherothrombotic atherothrombotic

eventevent5,6,75,6,7

Patients with a Patients with a history of history of

atherothrombosis atherothrombosis are most likely to are most likely to die of a recurrent die of a recurrent atherothrombotic atherothrombotic

eventevent5,6,75,6,7

Prevalence(Patients with

disease history)

Prevalence(Patients with

disease history)MortalityMortality

MI=myocardial infarction; PAD=peripheral arterial disease.†PAD patients in North America (USA and Canada): symptomatic (37.5%) and asymptomatic (62.5%).

1. Heart and Stroke Foundation of Canada. 5. Hardie K, et al. Stroke. 2003;34:1842-1846.2. Manuel DG, et al. Can J Cardiol. 2003;19:997-1004. 6. Taneja AK, et al. Eur Heart J. 2004;25:2013-2018.3. Ouriel K. Lancet. 2001;358:1257-1264. 7. Hirsch AT, et al. J Am Coll Cardiol. 2006;47:1239-1312.4. Weitz JI, et al. Circulation. 1996;94:3026-3049.

Stroke 40,000 – 50,0001

Stroke 40,000 – 50,0001

MI75,0001

MI75,0001

PADVariable depending

on population3

PADVariable depending

on population3

Incidences per yearIncidences per year

Page 51: Diffuse Vascular Disease (Focus on Peripheral Arterial Disease [PAD])

Patients with Previous Atherothrombotic Patients with Previous Atherothrombotic Events are at Increased Risk of Further EventsEvents are at Increased Risk of Further Events

Increased risk versus general population

MI Stroke

Ischemic stroke 2-3x(includes angina and sudden death*)1

9x2

MI 5-7x(includes death)3

3-4x(includes TIA)1

PAD 4x(includes only fatal MIand other CHD death†)4

2-3x(includes TIA)2

* Sudden death defined as death documented within one hour and attributed to coronary heart disease (CHD).† Includes only fatal MI and other CHD death; does not include non-fatal MI.

1. Kannel WB. J Cardiovasc Risk.1994;1:333–339.; 2. Wilterdink JL, et al. Arch Neurol. 1992;49:857–863. 3. Adult Treatment Panel II. Circulation. 1994;89:1333–1363. 4. Criqui MH, et al. N Engl J Med. 1992;326:381–386.

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Framingham Heart Study:Framingham Heart Study:Atherothrombosis Reduces Life ExpectancyAtherothrombosis Reduces Life Expectancy

0

5

10

15

20

Healthy History of MI History of CVA

In the FHS, healthy individuals aged 60 years who did not have atherothrombosis were expected to live a further 20 years to the age of 80 Comparatively, patients with a history of MI lived 9.2 fewer years Those with a history of CVA lived 12 fewer years

In the FHS, healthy individuals aged 60 years who did not have atherothrombosis were expected to live a further 20 years to the age of 80 Comparatively, patients with a history of MI lived 9.2 fewer years Those with a history of CVA lived 12 fewer years

9.2Feweryears

12Feweryears

Lif

e E

xpec

tan

cy (

Yea

rs) 2020

MI=myocardial infarction; CVA=cerebrovascular accident.Adapted from Bakhai A. Pharmacoeconomics. 2004;22(suppl 4):11-18.

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Atherothrombosis as a Cause of DeathAtherothrombosis as a Cause of Death

4.9%6.5%

9.1%

12.5%

19.1%

22.3%

0

5

10

15

20

25

Mo

rta

lity

(%

)

Athero-thrombosis

InfectiousDisease

Cancer Injuries PulmonaryDisease

AIDS

According to the World Health Organization in 2004 atherothrombosis was the leading cause of death worldwide—more than AIDS and cancer

According to the World Health Organization in 2004 atherothrombosis was the leading cause of death worldwide—more than AIDS and cancer

Bakhai A. Pharmacoeconomics. 2004;22(suppl 4):11-18.

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Economic Burden of AtherothrombosisEconomic Burden of Atherothrombosis

0

100

200

300

400

500

Cardiovascular Disease Cancer HIV

Indirect Costs

Direct Costs

The annual cost of CVD in 2006 was estimated to be higher than HIV and cancer in 2004

The annual cost of CVD in 2006 was estimated to be higher than HIV and cancer in 2004

$403.1 billion

Es

tim

ate

d C

os

t (i

n b

illi

on

s)

American Heart Association. Heart Disease and Stroke Statistics—2006 Update. 2006.

$190 billion

$28.9 billion

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