Primary Care Today
Download
1 / 95

Primary Care Today - PowerPoint PPT Presentation


  • 115 Views
  • Uploaded on

Primary Care Today Educational Conference and Medical Exposition Toronto, Ontario / May 8-10, 2008. Adapted from a presentation by: Alan D. Bell, MD, MCFP Humber River Regional Hospital Toronto, Ontario.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Primary Care Today' - adolfo


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

Primary Care Today

Educational Conference and Medical ExpositionToronto, Ontario / May 8-10, 2008

Adapted from a presentation by:

Alan D. Bell, MD, MCFP

Humber River Regional Hospital

Toronto, Ontario


The Optimal Management of Diffuse Vascular Disease: Clinical Implications of the Landmark REACH Registry


Program rationale
Program Rationale

Atherothrombosis remains the leading cause of death worldwide accounting for 47% of North American Mortality

In Canada there is one stroke every 10 minutes and 1 heart attack every 7 minutes

Need for Canadian primary care physicians to learn more about the management of patients with diffuse vascular disease

Suboptimal Risk Factor Management in C/V disease

42% of high risk atherothrombotic patients in REACH were not on evidence based risk reduction “triple therapy”

58% of Canadian high risk hypertensives NOT at goal BP in REACH were on fewer than 3 drugs


Learning objectives
Learning Objectives

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

  • Understand the epidemiology and burden of atherothrombosis

  • Understand the importance of registries and discuss the clinical implications of the REACH Registry

  • Describe the consequences of PAD and apply Canadian guidelines for the management of PAD

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

REACH: Reduction of Atherothrombosis for Continued Health; PAD: peripheral arterial disease


Question 1
Question 1

Which of the following are typical characteristics a Registry?

Registries examine the effects of a specific intervention

Registries usually have more exclusion criteria compared to randomized trials

Registries tell us about “real world” characteristics and outcomes

Registry results are less reliable than randomized trial results

All of the above


What is a registry
What is a Registry?

  • Organized system that collects data for scientific, clinical, or policy purposes

  • Complements RCTs by determining real-world outcomes

  • Generally do not:

    • Have restrictive inclusion or exclusion criteria

    • Specify what therapy the health care provider must adhere to

  • Often used to evaluate outcomes for diverse purposes:

    • Natural history of a disease

    • Real-world effectiveness of therapies, etc.

RCTs: randomized controlled trials


Example of a registry framingham heart study
Example of a Registry:Framingham Heart Study

  • Started in 1948

  • Objective:identify the common factors or characteristics that contribute to cardiovascular disease

  • 5209 men and women, ages 30-62, from Framingham, Massachusetts

  • Examinations every 2 years

  • Over 50 years of follow-up

NHLBI. Framingham Heart Study. Available at: www.nhlbi.nih.gov/about/framingham Accessed January 22, 2008.


Framingham heart study atherothrombosis reduces life expectancy
Framingham Heart Study:Atherothrombosis Reduces Life Expectancy

  • 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

20

12

Feweryears

Life Expectancy (Years)

CVA: cerebrovascular accident

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



Cardiovascular event rates in 68 000 outpatients with atherothrombosis registry results

Cardiovascular Event Ratesin >68,000 Outpatients with AtherothrombosisRegistry Results


Reach purpose
REACH: Purpose

  • Describe the characteristics and management of patients at high risk of atherothrombosis with and without symptomatic manifestations in any vascular bed

  • Assess long-term risk of atherothrombotic events

  • Compare outcomes

  • Assess the amount of “cross-risk”

  • Assess the impact of “diffuse vascular disease”

  • Define predictors of risk

Adapted from Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Inclusion criteria

At least

of four

criteria

At least

atherothrombotic

risk factors

Inclusion Criteria

  • Documented cerebrovascular diseaseIschemic stroke orTIA

  • Documentedcoronary diseaseAngina, MI, angioplasty/stent/bypass

  • Documented historicalor current intermittentclaudication associatedwith ABI* <0.9

  • Male ³65 yearsor female ³70 years

  • Current smoking>15 cigarettes/day

  • Type I or II diabetes

  • Hypercholesterolemia

  • Diabetic nephropathy

  • Hypertension

  • ABI <0.9 in eitherleg at rest

  • Asymptomatic carotidstenosis ³70%

  • Presence of at leastone carotid plaque

Must include

Signed

Written

Informed

Consent

Patients aged

≥45 years

1

3

*ABI: Ankle Brachial Index

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Reach registry 67 000 patients from 5 473 sites in 44 countries

1,976

REACH Registry: >67,000 Patients from 5,473 Sites* in 44 Countries

5,656

17,886

27,746

5,048

5,903

846

North America

1,931

Latin America

Western Europe

2,872

Eastern Europe

Middle East

*up to 15 patients/site (up to 20 in the US)

Asia (incl. Japan)

Australia

Adapted from Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


REACH Registry Timeline

Dec 2003 to

June 2004

June 2007 to June 2008

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


What does reach add to our current understanding of atherothrombosis
What Does REACH Add to Our Current Understanding of Atherothrombosis?

  • Global registry

  • Stable outpatients

  • Large number of primary-care patients

  • Includes multiple risk factor andmanifest vascular disease patients in all 3 vascular beds

  • 4 years of follow-up

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Baseline data

Published 11 Atherothrombosis?th Jan 2006: Bhatt DL, et al, for the REACH Registry Investigators.

JAMA 2006;295(2):180-9.

Baseline Data


Reach significant proportion of the symptomatic population has diffuse vascular disease
REACH: Atherothrombosis?Significant Proportion of the Symptomatic Population has Diffuse Vascular Disease*

Prevalence of disease in arterial beds (% of total)

Single arterial bed: 65.9%

CAD Alone

44.6

CVD Alone

16.6

PAD Alone

4.7

Diffuse vascular disease: 15.9%

CAD: coronary artery disease

PAD: peripheral arterial disease

CVD: cerebrovascular disease

CAD + CVD

8.4

CAD + PAD

4.7

CVD + PAD

1.2

CAD + CVD + PAD

1.6

Multiple risk factors: 18.3%

0

10

20

30

40

50

60

70

Patients (%)

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Reach patient characteristics at baseline
REACH: Patient Characteristics at Baseline Atherothrombosis?

% of population

Symptomatic(n=55,499)

Total

(n=67,888)

Multiple RF only

(n=12,389)

Mean age (SD) yr

68.5 (10.1)

68.4 (10.1)

69.0 (9.8)

Men

63.7

66.9

49.5

Diabetes

44.3

37.5

74.9

Hypertension

81.8

80.0

90.3

Hypercholesterolemia

72.4

70.2

82.2

Overweight (BMI 25 to < 30)

39.8

40.9

35.0

Obesity (BMI ≥ 30)

30.2

27.4

42.4

Former smoker

41.6

44.6

28.4

Current smoker

15.3

14.4

19.2

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Physician profile

Physician profile Atherothrombosis?

Follow-up available (%) N=63,129

General practice (N=24,441)

36.7

74.7

Internist (N=22,244)

32.8

12.3

Cardiologist (N=9,390)

14.0

9.7

Angiologist (N=771)

1.1

Vascular surgeon (N=1,480)

2.2

Neurologist (N=6,353)

9.4

3.2

Endocrinologist (N=1,987)

3.0

Other (N=533)

0.8

Physician Profile


Reach risk factors are consistently found across all disease subpopulations
REACH: Atherothrombosis?Risk Factors are Consistently Found Across All Disease Subpopulations*

Risk factor prevalence, by subpopulation (%)

100

CAD population

83.3

CVD population

81

80.3

77.0

80

PAD population

66.7

58.2

60

Patients (%)

44.2

38.3

37.4

40

29.9

23.8

24.5

23.7

20

14.3

13.0

0

Treated

Treated hyper-

Treated diabetes

Obesity(BMI ≥ 30)

Current smoker

hypertension

cholesterolemia

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Diffuse vascular disease
Diffuse Vascular Disease Atherothrombosis?

  • How often do patients have manifest disease in more than one vascular bed?


25% of the 40,258 patients with CAD also have atherothrombotic disease in other arterial territories

(%s are of total population)

Multiple risk factors only population

Patients with CAD = 59.3% of the REACH Registry population

CAD

44.6%

8.4%

CVD

1.6%

4.7%

CAD=coronary artery disease

PAD=peripheral arterial disease

CVD=cerebrovascular disease

PAD

  • Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


40% of the 18,843 patients with CVD also have atherothrombotic disease in other arterial territoriesatherothrombotic disease in other arterial territories

(%s are of total population)

Multiple risk factors only population

Patients with CVD = 27.8% of the REACH Registry population

CAD

8.4%

CVD

1.6%

16.6%

1.2%

CAD=coronary artery disease

PAD=peripheral arterial disease

CVD=cerebrovascular disease

PAD

  • Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


60% of the 8,273 patients with PAD also have atherothrombotic disease in other arterial territoriesatherothrombotic disease in other arterial territories

(%s are of total population)

Multiple risk factors only population

CAD

Patients with PAD = 12.2% of the total REACH Registry population

CVD

1.6%

4.7%

1.2%

CAD=coronary artery disease

PAD=peripheral arterial disease

CVD=cerebrovascular disease

PAD

4.7%

  • Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


1-Year Outcomes atherothrombotic disease in other arterial territories


Reach 1 year event curves for cv death mi stroke combined endpoints
REACH: atherothrombotic disease in other arterial territories1-year Event Curves for CV Death, MI, Stroke & Combined Endpoints

4.24% of these stable patients had an event within 1 year

5.0

n=64,977

4.5

Non-fatal stroke

Non-fatal MI infarction

4.0

CV death/MI/stroke

CV death

3.5

3.0

42% 10 year risk

Event distribution function (%)

2.5

2.0

1.5

1.0

0.5

0.0

0

1

2

3

4

5

6

7

8

9

10

11

12

Time in months

Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.


Reach 1 year cv event rates symptomatic vs multiple risk factor only
REACH atherothrombotic disease in other arterial territories1-year CV Event Rates: Symptomatic vs Multiple Risk Factor Only

% of population

Symptomatic(n=53,390)

Total

(n=64,977)

Multiple RF only

(n=11,766)

Death all cause

2.6

2.8

1.5

CV death

1.7

1.8

0.8

Non-fatal MI

1.1

1.2

0.8

Non-fatal stroke

1.7

1.9

0.8

CV death/MI/stroke

4.2

4.7

2.2

CV death/MI/stroke/ hospitalization for atherothrombotic events*

12.8

14.4

5.3

*Such as TIA, unstable angina, worsening of PAD; adjusted for age and gender

Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.


1 year cardiovascular event rates as function of number of symptomatic disease locations
1-year cardiovascular event rates as function of number of symptomatic disease locations*

All p values <0.001

*Pts with ³3 risk factors but no symptoms are counted as 0, even in the presence of asymptomatic carotid plaque or reduced ABI**TIA, unstable angina, other ischemic arterial event including worsening of peripheral arterial disease


Other outcomes leading to hospitalization since baseline
Other outcomes leading symptomatic disease locations*to hospitalization since baseline

Total

(N=63,129)

Symptomatic (N=51,685)

CAD

(N=37,542)

CVD

(N=17,451)

PAD

(N=7,674)

Multiple RF only

(N=11,444)

Unstable angina

4.2

4.9

6.3

3.4

4.5

1.1

TIA

1.4

1.5

1.2

3.2

1.8

0.6

Other ischemic arterial event (including worsening of PAD)

1.3

1.5

1.5

1.5

4.1

0.5

Chronic heart failure

3.1

3.4

4.2

3.2

4.1

1.4

Bleeding (leading to hospitalization and transfusion)

0.8

0.9

0.9

0.9

1.3

0.5


Major adverse event rates at one year as a function of age total population
Major adverse event rates at one year as a function of symptomatic disease locations*age: total population

Rates adjusted for risk factors


Geographical variation of 1 year cardiovascular event rates

North America (N=25,302) symptomatic disease locations*

Latin America

(N=1,718)

Western Europe

(N=16,487)

Eastern Europe

(N=5,579)

Middle East

(N=818)

Asia (N=5,559)

Australia (N=2,822)

Japan (N=4,844)

CV death

1.4

1.8

1.5

2.2

2.4

1.5

1.5

0.7

Non-fatal MI

1.3

0.9

1.1

1.2

2.2

0.8

1.0

0.8

Non-fatal stroke

1.1

2.5

1.5

3.5

2.1

2.3

1.0

1.6

CV death/MI/ stroke

3.7

4.9

3.7

6.8

6.3

4.5

3.2

3.0

CV death/MI/ stroke/ hospitalization for atherothrombotic events*

11.4

13.6

14.2

21.6

18.0

10.0

11.3

6.3

Geographical Variation of 1-year Cardiovascular Event Rates

*TIA, unstable angina, other ischemic arterial event including worsening of peripheral arterial disease


Undertreatment of risk factors at study entry
Undertreatment of Risk Factors at Study Entry symptomatic disease locations*

Bhatt DL, et al. JAMA 2006;295(2):180-9.


Take home messages
Take-Home Messages symptomatic disease locations*

  • 1-year REACH results reveal:

    • High rate of CV death, MI, and stroke (4.24%) in this “stable” outpatient population

    • Similar risk factor profiles regardless of vascular bed involved

    • Significant proportion of symptomatic patients with diffuse vascular disease

  • Rates increase markedly with the number of symptomatic disease locations (CV death/MI/stroke)

    • 1.5% (risk factors only)

    • 7.1% (triple location)


Atherothrombosis
Atherothrombosis symptomatic disease locations*


Atherothrombosis h as multiple manifestations
Atherothrombosis symptomatic disease locations*has Multiple Manifestations

Ischemic stroke

Transient ischemic attack (TIA)

Myocardial infarction

(MI)

  • Angina:

  • Stable

  • Unstable

  • Peripheral arterial disease (PAD):

  • Intermittent claudication

Rest pain

Gangrene

Necrosis

Adapted from Drouet L. Cerebrovasc Dis 2002;13(suppl 1):1–6.


Atherothrombosis a generalized and progressive disease
Atherothrombosis: symptomatic disease locations*A Generalized and Progressive Disease

Atherosclerosis

Unstable angina

MI

Ischemic stroke/TIA

Critical leg ischemia

Intermittent

claudication

CV death

ACS

Thrombosis

Stable angina/Intermittent claudication

Adapted from Libby P. Circulation 2001;104(3):365-372.


What types of lesions cause mi
What Types of Lesions Cause MI? symptomatic disease locations*

Coronary stenosis severity prior to MI

100

100

14%

80

80

18%

60

60

68%

Coronary Events (%)

40

40

20

20

0

0

Ambrose1988

Little1988

Nobuyoshi1991

Giroud1992

All 4studies

<50%

50%-70%

>70%

Falk E et al. Circulation 1995;92:657-71.


Pathology: Plaque Fissuring symptomatic disease locations*


Vascular disease is a leading cause of death worldwide

AIDS symptomatic disease locations*

5.1

Pulmonary disease

6

Injuries

9.1

Cancer

12.6

Infectious disease

17.8

Vascular Disease* is a Leading Cause of Death Worldwide†

Leading Causes Of Death, Worldwide

(% of all deaths)

Vascular disease*

28.7

0

5

10

15

20

25

30

Mortality (%)

*Ischemic heart disease, cerebrovascular disease, inflammatory heart disease and hypertensive heart disease

†Worldwide defined as Member States by World Health Organization (WHO) Region (Africa, Americas, Eastern Mediterranean, European, South-East Asia and Western Pacific)

AIDS: acquired immune deficiency syndrome

WHO. 2002. Available at: www.who.int/whr/2002/en/whr02_en.pdf


Atherothrombosis: Epidemiology symptomatic disease locations*

Epidemiology of Atherothrombotic Manifestations in Canada


Peripheral arterial disease and the canadian pad guidelines
Peripheral Arterial Disease symptomatic disease locations*and theCanadian PAD Guidelines


Question 2
Question 2 symptomatic disease locations*

How common is peripheral arterial disease (PAD) in your practice?

I hardly ever see it – It’s a specialist disease

I have a few patient’s, but it’s much less common than coronary disease

Since I’ve been screening for it I can’t believe how common it is!

I don’t know, because I have no way to test for it

I don’t look for it because none of my patients ever died of a “leg attack”


PAD: Epidemiology symptomatic disease locations*

  • Often asymptomatic, under-diagnosed, under-recognized, and under-treated

  • 16% of North America and Europe has PAD, corresponding to 27 million people

  • Of these, 16.5 million are asymptomatic

Gupta A. In: Abramson BL, et al. Can J Cardiol 2005;21(12):997-1006.


CCS Guidelines: Diagnosis of PAD symptomatic disease locations*

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


Edinburgh questionnaire
Edinburgh Questionnaire symptomatic disease locations*

  • Do you get a pain or discomfort in you leg(s) when you walk?

    • YES

  • 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

  • What happens to it if you stand still?

    • Pain usually disappears in 10 minutes or less

  • Where do you get this pain or discomfort?

    • Patient marks calf and/or thigh and/or buttock

91.3% Sensitive 99.3% specific

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


Measuring abi

Right-arm symptomatic disease locations*

systolic

pressure

Left-arm

systolic

pressure

INTERPRETATION OF ABI

>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

DP

PT

DP

PT

Left-ankle

systolic pressure

Right-ankle

systolic pressure

Measuring ABI

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


Question 3
Question 3 symptomatic disease locations*

Which of the following are TRUE regarding symptomatic PAD?

30% will suffer a fatal vascular event within 5 years

Ankle / Brachial Index (ABI) is sensitive and specific enough to make the diagnosis of PAD

Severity of disease and mortality may be predicted by ABI

Exercise programs can improve claudication symptoms

All of the above


Consequences of pad may be local and systemic
Consequences of PAD may be symptomatic disease locations*Local and Systemic

  • Local consequences in the leg include:

    • Intermittent claudication

    • Tissue loss including sepsis and major amputations

  • PAD is a marker of disease in other vascular beds

    • Fatal and non-fatal cerebral and coronary vascular events

REACH: Reduction of Atherothrombosis for Continued Health


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

* Sudden death defined as death documented within 1 hour and attributed to coronary heart disease (CHD).

† Includes only fatal MI and other coronary heart disease (CHD) death; does not include non-fatal MI.

1. Kannel WB. J Cardiovasc Risk1994;1(4):333–339.; 2. Wilterdink JL, et al. Arch Neurol 1992;49(8):857–863. 3. Adult Treatment Panel II. Circulation 1994;89(3):1333–1363. 4. Criqui MH, et al. N Engl J Med 1992;326(6):381–386.


Consequences of pad
Consequences of PAD Increased Risk of Further Events

5-year natural history of intermittent claudication

Population > 55 years of age

Intermittent claudication 5%

5-year peripheral vascular outcomes

Other cardiovascular outcomes

Major amputation

<4%

Surgery or tissue loss

>25%

Worsening claudication

~16%

Stable claudication

~50%

5-year mortality

30%

5-year non-fatal atherothrombotic events (MI, stroke, etc.)

20%

Adapted from Weitz JI, et al. Circulation 1996;94(11):3026-3049.


Risk of death is increased in patients with both asymptomatic and symptomatic pad
Risk of Death is Increased in Patients with Both Asymptomatic and Symptomatic PAD

100

Survival (% of patients)

75

50

25

Symptomatic PAD†

Normal subjects*

Asymptomatic PAD†

Severe symptomatic PAD†

0

4

8

10

0

2

6

12

Year

* Kaplan-Meier survival curves based on mortality from all causes.

† Large-vessel PAD.

Criqui MH, et al. N Engl J Med 1992;326(6):381-386.


Getabi mortality all cause by abi category

> 1.1 Asymptomatic and Symptomatic PAD

0.9 – 1.1

0.7 – 0.9

0.5 – 0.7

< 0.5

GetABI: Mortality (All-cause) by ABI Category

Proportion alive

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


Pad a major health burden
PAD: A Major Health Burden Asymptomatic and Symptomatic PAD

  • Patients with symptomatic PAD have a

  • 5-year mortality rate of 28%

    • compared with 15% for breast cancer

    • and 18% for Hodgkin’s disease1

  • Patients with PAD are 6 X more likely to die within 10 years than those without PAD1

Criqui MH, et al. N Eng J Med 1992;326(6):381-386.

Gupta A. In: Abramson BL, et al. Can J Cardiol 2005;21(12):997-1006.


Pad a major health burden1
PAD: A Major Health Burden Asymptomatic and Symptomatic PAD

  • Patients with PAD are 6 X more likely to die within 10 years than those without PAD1

  • Patients with PAD often have decreased quality of life because of pain during walking and limitations in mobility2

Criqui MH, et al. N Eng J Med 1992;326(6):381-386.

Belch JJ, et al. Arch Int Med 2003;163(8):884-892.


Question 4
Question 4 Asymptomatic and Symptomatic PAD

What are the most powerful risk factor(s) for development of PAD?

Risk factors for PAD are similar to those in all vascular beds

Smoking is more predictive for PAD than the other traditional risk factors

Diabetes is more predictive for PAD than the other traditional risk factors

All of the above


Risk Factors for PAD Asymptomatic and Symptomatic PAD

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

  • Age

  • Family history

  • Male sex

  • Cigarette smoking

  • Diabetes

  • Elevated lipid levels

  • Hypertension

  • Obesity

  • Sedentary lifestyle

Teo KK. In: Abramson BL, et al. Can J Cardiol 2005;21(12):997-1006.


Reach risk factors are consistently found across all disease subpopulations1

100 Asymptomatic and Symptomatic PAD

CAD population

83.3

CVD population

81

80.3

77.0

80

PAD population

66.7

58.2

60

44.2

Patients (%)

38.3

37.4

40

29.9

23.8

24.5

23.7

20

14.3

13.0

0

Treated

Treated hyper-

Treated diabetes

Obesity(BMI ≥ 30)

Current smoker

hypertension

cholesterolemia

REACH: Risk Factors are Consistently Found Across All Disease Subpopulations*

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Take home messages1
Take-Home Messages Asymptomatic and Symptomatic PAD

  • Atherothrombosis is a generalized and progressive disease

  • Acute vascular events are the result of sudden plaque rupture

  • PAD is associated with significant morbidity and mortality due to local and systemic complications

  • Currently, PAD is under-diagnosed and under-treated

  • Cigarette smoking and diabetes are the strongest risk factors for PAD


Hyperlinks to patient vignettes

Vignette 3: John Asymptomatic and Symptomatic PAD

63-year-old government employee with recently

diagnosed PAD

Vignette 2: Todd

58-year-old retired executive with PAD who experienced

a MI 6 months ago ( i.e., diffuse vascular disease)

Vignette 1: Louise

56-year-old female who experienced a mild ischemic stroke

6 months ago and has since made a full recovery

Hyperlinks to Patient Vignettes


Patient vignette louise
Patient Vignette: Louise Asymptomatic and Symptomatic PAD

  • Louise is a 56-year-old office manager

  • 6 months ago she experienced a mild ischemic stroke

  • She has since made a full recovery with no residual signs/symptoms

  • Her current medications include anti-platelet therapy, an ACE inhibitor and a statin

  • Louise comes to your office today for a routine visit and tells you that she would like to return to work


Question 5
Question 5 Asymptomatic and Symptomatic PAD

Which of the following in NOT appropriate Anti-platelet therapy for Louise?

ER Dipyrdamole 200 mg plus ASA 25 mg BID

ECASA 81 mg plus clopidogrel 75 mg OD

ECASA 81 - 325 mg OD alone

Clopidogrel 75 mg OD alone

None of the above, all are reasonable


Match results

18 Asymptomatic and Symptomatic PAD

12

6

0

MATCH: Results

Cumulative Event Rate

(Ischemic Stroke, MI, Vascular Death,

Rehospitalization due to Ischemic Event)

Placebo

6.4% RRR

1.03% ARR

P=0.244

ASA

Cumulative event rate (%)

On-Treatment Analysis: 9.6% RRR, 1.6% ARR, p=0.10

0

1

3

6

12

18

Months of follow-up

* All patients received clopidogrel background therapy

Diener HC, et al. Lancet. 2004; 364:331-337.


Esps 2 risk reduction for stroke or death
ESPS 2: Asymptomatic and Symptomatic PADRisk Reduction for Stroke or Death

P<0.001

P=0.006

P<0.05

P<0.05

Stroke relative risk reduction (%)

n = 6602 within 3 months of stroke or TIA

2 years of follow-up

ER DP = extended release dipyridamole

Diener HC, et al. J Neurol Sci. 1996;143:1-13.


Antithrombotic trialists collaboration
Antithrombotic Trialists’ Collaboration Asymptomatic and Symptomatic PAD

ASA dose

500 – 1500 mg daily

160 – 325 mg daily

75 – 150 mg daily

< 75 mg daily

Any ASA dose

% odds reduction*

75-150 mg ASA daily is at least as effective as higher daily ASA doses which carry higher risk of GI bleeding

23% + 2

(P<0.0001)

0.0

0.5

1.0

1.5

Control better

ASA better

*Vascular events = MI, stroke or vascular death

Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86.


CAPRIE: Asymptomatic and Symptomatic PADClopidogrel vs ASA in Patients with Previous Acute Events

Outcome = IS, MI, vascular death

  • Patients with previous acute events

14.9%

  • Entire CAPRIE sample

8.7%

Outcome = IS, MI, rehospitalization for angina/ claudication/peripheral ischemia/TIA/MI

12.0%

  • Patients with previous acute events

  • Entire CAPRIE sample

9.0%

30

20

0

10

20

40

10

Clopidogrel better

ASA better

CAPRIE: Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events

Ringleb PA, et al. Stroke. 2004;35:528-532.


2006 AHA/ASA Guidelines: Asymptomatic and Symptomatic PADPrevention of Stroke in Patients with Ischemic Stroke or TIA

Antithrombotic Therapy for Non-Cardioembolic Stroke or TIA

Sacco RL, et al. Stroke. 2006;37:577–617.


Question 6
Question 6 Asymptomatic and Symptomatic PAD

With regard to her future vascular risk:

Her greatest risk of death in the next 12 months is recurrent stroke

There is a high probability that she has atherothrombotic disease in the coronary and peripheral circulation

Long term she is more likely to die from recurrent stroke than cardiac disease

All of the above

None of the above


Reach overlapping manifestations of disease
REACH: Asymptomatic and Symptomatic PADOverlapping Manifestations of Disease

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

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Long term cause of stroke mortality risk at 5 years
Long-Term Cause of Stroke Asymptomatic and Symptomatic PADMortality Risk at 5 Years

  • Cause of death

    • First stroke

    • Recurrent stroke

    • Cardiovascular disease

    • Nonvascular disease

    • Unknown

100

90

80

70

60

%

50

40

30

20

10

0

< 30d

30d–6m

6m–1yr

1-3yr

3-5yr

Time since first-ever stroke

Hankey GJ, et al. Stroke 2000;31(9):2080-2086.


Question 7 suppose louise also experienced an acute coronary syndrome within the past year
Question 7 - Asymptomatic and Symptomatic PADSuppose Louise also experienced an Acute Coronary Syndrome within the past year.

How would this impact her risk for subsequent atherothrombotic events?

She remains at equally high risk regardless of the presence of diffuse vascular disease

Her risk reduction strategies should remain unchanged

She would benefit from dual anti-platelet therapy with ASA 81 mg plus clopidogrel 75 mg

More aggressive lipid and blood pressure targets should be applied

All of the above


Cure primary endpoint mi stroke cv death n 12 562
CURE Primary Endpoint: Asymptomatic and Symptomatic PADMI/Stroke/CV Death (n=12,562*)

0.14

Placebo + ASA†

20%

Relative

Risk Reduction

p=0.00009

0.12

0.10

Clopidogrel + ASA†

0.08

Cumulative Hazard Rate

0.06

The primary outcome occurred in 9.3% of patients in the clopidogrel + ASA group and 11.4% in the placebo + ASA group

0.04

0.02

0.00

9

0

6

12

3

Months of Follow-up

CURE: Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events

* Study subjects had ACS (Acute Coronary Syndrome - UA/non–Q-wave MI).

†Other standard therapies were used as appropriate.

CURE Trial Investigators. N Engl J Med 2001;345(7):494-502.


Cure major bleeding by asa dose
CURE: Asymptomatic and Symptomatic PADMajor Bleeding by ASA Dose

6.0

5.0

Placebo*

4.9

4.0

Clopidogrel*

4.0

3.5

Bleeding rate (%)

3.0

2.6

2.3

2.0

2.0

1.0

0.0

<100 mg

> 200 mg

100-200 mg

ASA dose 75-325 mg

*In addition to standard therapy (including ASA).

CURE Trial Investigators. N Engl J Med 2001;345(7):494-502.


REACH: 1-year CV Event Rates as a Function of the Number of Symptomatic Disease Locations

P<0.001

Risk sharply increases with

diffuse vascular disease

CV death/MI/stroke/hospitalization (%)

*

Number of disease locations

*Multiple risk factor group

Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.


HOPE: Risk Reduction with ACE Inhibition Symptomatic Disease Locations

CVD death

Stroke

Non-fatal MI

Total morality

16%

20%

p=0.005

p<0.001

26%

p<0.001

32%

p<0.001

Minimal changes in BP; non-hypertensive sub-group noted similar benefit

HOPE: Heart Outcomes Prevention Evaluation

Yusuf S, et al. N Engl J Med 2000;342(3):145-153.


PROGRESS: Stroke Reduction Symptomatic Disease Locations

0.20

6,105 subjects with cerebrovascular event within past 5 years

No BP entry requirement

0.15

Proportion with event

0.10

28% risk reduction

95%CI 17–38%

P<0.0001

ARR (%) = 4.0

0.05

placebo

perindopril-based treatment

1

2

3

4

Follow-up time (years)

PROGRESS: Perindopril Protection Against Recurrent Stroke Study

PROGRESS Collaborative Group. Lancet 2001;358(9287):1033-1041.


SPARCL: Symptomatic Disease Locations

Primary End-point: Fatal or Non-fatal Stroke

16% RRR*

HR 0.84 (0.71–0.99)

P=0.03

Placebo

16

12

Atorvastatin

8

Fatal/ nonfatal stroke(%)

4

0

0

1

2

3

4

5

6

Time since randomization (years)

SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol Levels

*Adjusted

The SPARCL Investigators. N Eng J Med 2006;355(6):549-559.


Caprie clopidogrel vs asa in multi bed disease
CAPRIE: Symptomatic Disease LocationsClopidogrel vs. ASA in Multi-bed Disease

15

10.74%

22.7%

10

8.35%

Annual event rate (%)

Relative Risk

Reduction

164 events

196 events

5

0

ASA

Clopidogrel

Events = ischemic stroke, MI or vascular death

CAPRIE: Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events

CAPRIE Steering Committee. Lancet 1996;348(9038):1329-1339.


Charisma treatment effect by inclusion criteria
CHARISMA: Symptomatic Disease LocationsTreatment Effect by Inclusion Criteria

Combined endpoint: MI, stroke, CV death

Hazard ratio

RR (95% CI)

Asymptomatic*

n=3284

1.20 (0.91–1.59)

P=0.20

Symptomatic†

n=12,153

0.88 (0.77–0.998)

P=0.046

All patients

n=15,603

0.93 (0.83–1.05)

P=0.22

0.5

1.0

1.5

Clopidogrel

Placebo

better

better

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

*Multiple atherothrombotic risk factors

†Documented CAD, CVD and/or PAD

Bhatt DL, et al. N Engl J Med 2006;354(16):1706-1717.


Take home messages2
Take-Home Messages Symptomatic Disease Locations

  • Approximately 40% of patients with CVD in the REACH Registry had diffuse vascular disease

  • Compared with a history of disease in a single vascular bed, diffuse vascular disease doubles the risk of a major CV event or hospitalization within 1 year

  • Aggressive risk reduction strategies including ACE inhibition, statins and antiplatelet therapy should be considered for patients with diffuse vascular disease

  • CHARISMA showed that patients with a prior atherothrombotic event benefit from long-term dual antiplatelet therapy (median follow-up 27 months)


Patient vignette john
Patient Vignette: John Symptomatic Disease Locations

  • John is a 63-year-old government employee

  • Last month, he came to your office complaining of left calf pain when walking a couple of blocks; the pain went away after a few minutes

  • Based on your history and clinical examination at this time, you suspected John had symptomatic PAD and sent him for an ABI

  • John’s ABI was 0.90 (R) 0.77 (L), which confirmed your diagnosis

ABI: ankle brachial index


Question 8
Question 8 Symptomatic Disease Locations

Unless contraindicated, which of the following are necessary risk reduction strategies for John?

Statin therapy to reduce LDL to < 2.0 mmol/L

RAA inhibition with an ACEI or ARB

Anti-platelet agent

Referral to a vascular surgeon

All of the above

a, b and c only


CCS Guidelines for PAD: Symptomatic Disease LocationsRisk Reduction Strategies

CCS: Canadian Cardiovascular Society; ACE: angiotensin-converting enzyme

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


CCS Guidelines for PAD: Symptomatic Disease LocationsPharmacological Approach

Medical therapies to reduce cardiovascular events in PAD

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


Reach 3 5 of patients with symptomatic pad have diffuse vascular disease
REACH: ~ 3/5 of Patients with Symptomatic PAD have Diffuse Vascular Disease

~ 3/5 of the 8,273 patients with PAD also haveatherothrombotic disease in other arterial territories

(%s are of total population)

CAD

Patients with PAD = 12.2% of the total REACH Registry population

CVD

1.6%

4.7%

1.2%

PAD

4.7%

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Consequences of pad1
Consequences of PAD Diffuse Vascular Disease

5-year natural history of intermittent claudication

Population > 55 years of age

Intermittent claudication 5%

5-year peripheral vascular outcomes

Other cardiovascular outcomes

Major amputation

<4%

Surgery or tissue loss

>25%

Worsening claudication

~16%

Stable claudication

~50%

5-year mortality

30%

5-year non-fatal atherothrombotic events (MI, stroke, etc.)

20%

Adapted from Weitz JI, et al. Circulation 1996;94(11):3026-3049.


Reach vascular interventions at 1 year
REACH: Diffuse Vascular DiseaseVascular Interventions at 1 Year

Total symptomatic (n=53,390)

CAD

(n=38,602)

CVD

(n=18,013)

PAD

(n=8,581)

Multiple RF only

(n=11,966)

Coronary angioplasty/ stenting

2.9

3.8

1.5

2.4

0.9

CABG

1.1

1.4

0.7

1.0

0.5

Carotid angioplasty/ stenting

0.3

0.3

0.4

0.6

0.2

Carotid surgery

0.5

0.4

0.7

1.0

0.3

Peripheral bypass graft

0.8

0.6

0.5

3.7

0.2

PAD angioplasty/ stenting

1.2

1.0

0.9

5.0

0.4

Amputation

0.4

0.3

0.3

1.6

0.3

Local Systemic

CABG: coronary artery bypass graft; adjusted for age and gender

Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.


REACH: Diffuse Vascular DiseaseVascular Interventions at 1 Year

Revascularization at 1 year (%)

(n=18,013)

(n=38,602)

(n=8,581)

Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.


Question 9
Question 9 Diffuse Vascular Disease

Which of the following anti-platelet strategies are NOT appropriate for John?

ASA 81 mg OD

Clopidogrel 75 mg OD

ASA 81 mg OD plus Clopidogrel 75 mg OD

ER Dipyrdamole 200 mg plus ASA 25 mg BID

None of the above (all are appropriate)


CCS Guidelines: Diffuse Vascular DiseaseAntithrombotic Therapies

*Not available in Canada

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


Question 10
Question 10 Diffuse Vascular Disease

What percentage of symptomatic Canadian REACH Registry patients are currently on “Triple Therapy” (ACE or ARB + Statin + Anti-platelet agent)

  • 95 %

  • 80 %

  • 75 %

  • 70 %

  • < 60 %


REACH: Proven Therapies are Consistently Underused in All Patient Types*

Patients receiving proven therapy (%)

(n=12,389)

(n=40,258)

(n=18,843)

(n=8,273)

ARB: angiotensin II receptor blocker

*Data shown may differ slightly from published abstracts owing to a subsequent database lock

Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.


Crusade link between guideline adherence and in hospital mortality
CRUSADE: Patient TypesLink Between Guideline Adherence and In-hospital Mortality

Improved Guideline Adherence

CRUSADE : Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC/AHA Guidelines

  • Adjusted figures

  • Peterson ED, et al. ACC Annual Scientific Session. 2004. Available at: http://www.crusadeqi.com


Approximately 1 in 5 patients with PAD will experience CV death, MI, stroke, or hospitalization within 1 year

Take-Home Messages

Breakdown of event rates



PAD

21.1% 1 in ~5



CAD

15.2% 1 in ~6



CVD

14.5% 1 in ~7

Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.


Take home messages continued
Take-Home Messages (continued) death, MI, stroke, or hospitalization within 1 year

  • ~ 60% of patients with PAD have diffuse vascular disease

  • ~ 15% of patients with PAD will require a vascular intervention at 1 year

  • Lifelong antiplatelet therapy with ASA or clopidogrel is recommended for patients with PAD

  • Adherence to guideline recommendations may lead to reduced mortality in PAD


ad