CVD Critical Pathways Group 2006 Teleconferences

1
CVD Critical Pathways Group 2006 Teleconferences
February 15, 2006
This activity is supported by an educational
grant from the Bristol-Myers Squibb/Sanofi
Pharmaceuticals Partnership.
2
Faculty

• Christopher P. Cannon, MD
• Associate Professor of Medicine
• Harvard Medical School
• Senior Investigator, TIMI Study Group
• Associate Physician, Cardiovascular Division
• Brigham and Womens Hospital
• Boston, Massachusetts

3
Disclosure Statement

• The Network for Continuing Medical Education
  requires that CME faculty disclose, during the
  planning of an activity, the existence of any
  personal financial or other relationships they or
  their spouses/partners have with the commercial
  supporter of the activity or with the
  manufacturer of any commercial product or service
  discussed in the activity.

4
Faculty Disclosure Statement

• Christopher P. Cannon, MD, has served as a
  consultant to AstraZeneca Pharmaceuticals LP,
  Bristol-Myers Squibb Company, GlaxoSmithKline,
  Guilford Pharmaceuticals, Merck/Schering-Plough
  Pharmaceuticals, Pfizer Inc, sanofi-aventis,
  Schering-Plough Corporation, and Vertex
  Pharmaceuticals Inc. He has also received
  research support from AstraZeneca Pharmaceuticals
  LP, Bristol-Myers Squibb Company, Merck Co.,
  Inc., and sanofi-aventis.
• The team from Maricopa Medical Center reports no
  such relationships.

5
Applying the New ACC/AHA Guidelines for
Peripheral Arterial Disease
Christopher P. Cannon, MD
6
Polling Question 1
How often do you use the ankle-brachial index to
screen for peripheral arterial disease in
asymptomatic patients?

• All of the time
• Most of the time
• Occasionally
• Never

7
Peripheral Arterial Disease (PAD)

• Defined as the presence of a stenosis or
  occlusion in the aorta or arteries of the limbs
• Usually caused by atherosclerosis
• Associated with an increased risk of
  cardiovascular and cerebrovascular events,
  including death, MI, and stroke
• May impair walking ability and threaten the limb

Belch JJF, et al. Arch Intern Med.
2003163884-892.
8
Overlap of Atherosclerotic Disease
38 overlap ?2 vascular beds
Patients with one manifestation often have
coexistent disease in other vascular beds.
Ness J, Aronow WS. J Am Geriatr Soc.
1999471255-1256.
9
PAD Clinical Presentations
Hiatt WR. N Engl J Med. 20013441608-1621.
10
PAD Survival Curve
1.00
Normal Subjects
0.75
Asymptomatic PAD
Percent Survival
0.50
Symptomatic PAD
Severe Symptomatic PAD
0.25
0.00
12
10
8
6
4
2
0
Year
Reprinted with permission from Criqui MH, et al.
N Engl J Med. 1992326381-386.
11
ACC/AHA 2006 PAD Management GuidelinesClinical
Presentation Asymptomatic

• A history of walking impairment, claudication,
  ischemic rest pain, and/or nonhealing wounds is
  recommended as a required component of a standard
  review of systems for adults 50 years and older
  who have atherosclerosis risk factors and for
  adults 70 years and older.

C
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
12
ACC/AHA 2006 PAD Management GuidelinesClinical
Presentation Asymptomatic

• Individuals with asymptomatic lower extremity PAD
  should be identified by examination and/or
  measurement of the ankle-brachial index (ABI) so
  that therapeutic interventions known to diminish
  their increased risk of myocardial infarction
  (MI), stroke, and death may be offered.

B
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
13
Claudication and Mortality
Follow-up in 2777 patients with claudication over
11 years
Predictors of Death

• Diabetes
• Age

• Prior Stroke
• Lower ABI

1.0
0.8
Survival
0.6
0.4
Number at risk
0.2
2777
1706
787
286
10
0
1
2
3
4
5
6
7
8
9
Years
Reprinted with permission from Muluk SC, et al. J
Vasc Surg. 200133251-258.
14
ACC/AHA 2006 PAD Management GuidelinesClinical
Presentation Claudication

• Patients with symptoms of intermittent
  claudication should undergo a vascular physical
  examination, including measurement of the
  ankle-brachial index (ABI).

B
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
15
Association Between
Ankle-Brachial Index (ABI) and
Mortality
All-cause mortality CVD mortality
70
60
50
40
Percent ()
30
20
10
/ /
0
lt0.60(n25)
?1.50(n89)
Incom-pressible (n179)
0.90-lt1.0(n195)
1.0-lt.1.10(n980)
0.60-lt0.70(n21)
0.70-lt0.80(n40)
0.80-lt0.90(n130)
1.40-lt.1.50(n136)
Baseline ABI
Adapted from Resnick HE, et al. Circulation.
2004109733-739.
16
ACC/AHA 2006 PAD Management GuidelinesDiagnostic
Methods Ankle-Brachial Index (ABI)

• The resting ABI should be used to establish the
  lower extremity PAD diagnosis in patients with
  suspected lower extremity PAD, defined as
  individuals with exertional leg symptoms, with
  nonhealing wounds, who are 70 years and older, or
  who are 50 years and older with a history of
  smoking or diabetes.

C
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
17
Risk Factors for PAD
Smoking Diabetes Hypertension Hypercholesterolemia
Hyperhomocysteinemia C-Reactive Protein
Relative Risk
1
2
3
4
5
6
0
Dormandy JA, Rutherford RB, for the TASC Working
Group. J Vasc Surg. 200031(1 pt 2)S1-S288.
18
Effect of Smoking Cessation on Survival in
Patients With PAD
133 patients observed after bypass graft or
lumbar sympathectomy
Cumulative Survival,
Australian census Tobacco abstinence Continued
tobacco use
5
4
3
2
1
0
Years Postoperative
Faulkner KW, et al. Med J Aust. 19831217-219.
19
ACC/AHA 2006 PAD Management GuidelinesCV Risk
Reduction Smoking Cessation

• Individuals with lower extremity PAD who smoke
  cigarettes or use other forms of tobacco should
  be advised by each of their clinicians to stop
  smoking and should be offered comprehensive
  smoking cessation interventions, including
  behavior modification therapy, nicotine
  replacement therapy, or bupropion.

B
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
20
Heart Protection StudyVascular Event by Prior
Disease
BaselineFeature
Risk ratio and 95 CI STATIN
STATIN Better Worse
STATIN (10,269)
PLACEBO (10,267)
Previous MI 999 1250 (23.5) (29.4) Other
CHD (not MI) 460 591 (18.9) (24.2)


No prior CHD CVD 172 212 (18.7) (23.6) PAD
n3748 327 420 (24.7) (30.5) Diabetes
276 367 (13.8) (18.6) ALL
PATIENTS 2033 2585 (19.8) (25.2)
24 SE 3 reduction (2Plt.001)
0.4
0.6
0.8
1.0
1.2
1.4
Reprinted with permission from Heart Protection
Study Collaborative Group. Lancet.
20023607-22.
21
ACC/AHA 2006 PAD Management GuidelinesCV Risk
Reduction Lipid-Lowering Drugs

• Treatment with a hydroxymethyl glutaryl
  coenzyme-A reductase inhibitor (statin)
  medication is indicated for all patients with PAD
  to achieve a target low-density lipoprotein (LDL)
  cholesterol level of less than 100 mg per dL.
• Treatment with a statin medication to achieve a
  target LDL-C level of less than 70 mg per dL is
  reasonable for patients with lower extremity PAD
  at very high risk of ischemic events.

B
B
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
22
Intensive BP Therapy in PADThe ABCD Trial
50
Moderate treatment (137/81) n227
Intensive treatment (128/75) n220
40
30
Odds of MI, Stroke, or Vascular Death
20
10
0
1.3
1.2
1.1
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Baseline ABI
enalapril or nisoldipine ABCD Appropriate
Blood Pressure Control in Diabetes study ABI
ankle-brachial index. Reprinted with permission
from Mehler PS, et al. Circulation.
2003107753-756.
23
ACC/AHA 2006 PAD Management Guidelines CV Risk
Reduction Antihypertensive Drugs

• Antihypertensive therapy should be administered
  to hypertensive patients with lower extremity
  PAD to achieve a goal of less than 140 mm Hg
  systolic over 90 mm Hg diastolic (nondiabetics)
  or less than 130 mm Hg systolic over 80 mm Hg
  diastolic (diabetics and individuals with chronic
  renal disease) to reduce the risk of MI, stroke,
  congestive heart failure, and cardiovascular
  death.

A
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
24
UKPDS Intensive Blood Glucose Control vs
Conventional Treatment in Patients With Type 2
Diabetes
RR
Favors
Favors
Log-rank
intensive
P value
conventional
1
10
Clinical End Point
Any diabetes-related end point
.029
0.88
Diabetes-related deaths
.34
0.90
All-cause mortality
.44
0.94
MI
.052
0.84
Stroke
.52
1.11
Amputation or death from PVD
.15
0.65
Microvascular disease
.0099
0.75
RR relative risk PVD peripheral vascular
disease. Reprinted with permission from UKPDS
Group. Lancet. 1998352837-853.
25
ACC/AHA 2006 PAD Management Guidelines CV Risk
Reduction 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.

C
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
26
Antithrombotic Trialists Collaboration MI,
Stroke, CV Death in Patients With PAD

• Category APT CTRL Reduction ()
• Intermittent 6.4 7.9 239
• claudication
• Peripheral artery 5.4 6.5 2216
• bypass graft
• Peripheral 2.5 3.6 2935
• angioplasty
• All high-risk patients 222
• (Plt.001)

1.0
0.5
0.0
1.5
2.0
Reprinted with permission from Antithrombotic
Trialists Collaboration. BMJ. 200232471-86.
27
ACC/AHA 2006 PAD Management Guidelines CV Risk
Reduction Antiplatelet Therapy

• Antiplatelet therapy is indicated to reduce the
  risk of MI, stroke, or vascular death in
  individuals with atherosclerotic lower extremity
  PAD.

Aspirin, in daily doses of 75 mg to 325 mg, is
recommended as safe and effective antiplatelet
therapy to reduce the risk of MI, stroke, or
vascular death in individuals with
atherosclerotic lower extremity PAD.
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
28
CAPRIE Study
Efficacy of Clopidogrel in Primary Analysis of
MI, Ischemic Stroke, or Vascular Death
20
Aspirin
8.7 Relative Risk Reduction
15
Clopidogrel
Cumulative Event Rate,
10
Aspirin
Clopidogrel
5
P.043
0
36
30
18
3
15
0
33
27
24
21
6
9
12
Months of Follow-up
ITT analysis. CAPRIE Clopidogrel vs Aspirin in
Patients at Risk of Ischemic Events. Reprinted
with permission from CAPRIE Steering Committee.
Lancet. 19963481329-1339.
29
CAPRIE Study
Relative Risk Reduction and 95 CI by Disease
Subgroup
Stroke
MI
PAD
All patients
40
30
20
10
0
10
20
30
40
Aspirin Better
Clopidogrel Better
Reprinted with permission from CAPRIE Steering
Committee. Lancet. 19963481329-1339.
30
ACC/AHA 2006 PAD Management Guidelines CV Risk
Reduction Antiplatelet Therapy

• Clopidogrel (75 mg per day) is recommended as an
  effective alternative antiplatelet therapy to
  aspirin to reduce the risk of MI, stroke, or
  vascular death in individuals with
  atherosclerotic lower extremity PAD.

B
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
31
Meta-Analysis of Exercise Training in
Claudication
200
Exercise Training
180
Control
160
140
120
Change in Treadmill Walking Distance,
100
80
60
40
20
0
Onset of Claudication Pain
Maximal Claudication Pain
Gardner AW, Poehlman ET. JAMA.1995274975-980.
32
Relative Efficacy of Supervised vs Unsupervised
Exercise Training
MWD maximal walking distance PFWD pain-free
walking distance. Regensteiner JG, et al.
Angiology. 199748291-300.
33
ACC/AHA 2006 PAD Management GuidelinesExercise
and Lower Extremity PAD Rehabilitation

• A program of supervised exercise training is
  recommended as an initial treatment modality for
  patients with intermittent claudication.

A
Supervised exercise training should be performed
for a minimum of 30 to 45 minutes, in sessions
performed at least 3 times per week for a minimum
of 12 weeks.
A
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
34
Effect of Cilostazol on Walking Distance in
Patients With Claudication

260
MaximalWalking Distance

240

220

Cilostazol 100 mg bid (n140) Cilostazol 50 mg
bid (n139) Placebo (n140)
200



180

Meters Walked (mean)

160


140

Pain-FreeWalking Distance


120



100



80
Plt.05 vs placebo
60







0
4
8
12
16
20
24
Weeks of Treatment
Beebe HG, et al. Arch Intern Med.
19991592041-2050.
35
Effect of Cilostazol vs Pentoxifylline on Walking
Distance in Patients With Claudication
50
Cilostazol 100 mg bid po Pentoxifylline 400 mg
tid Placebo
40

30
Percent Change From Baseline MWD (mean)
20
Plt.05 at all time points
10
0
0
4
8
12
16
20
24
Weeks of Treatment
Reprinted with permission from Dawson DL, et al.
Am J Med. 2000109523-530.
36
ACC/AHA 2006 PAD Management GuidelinesMedical
and Pharmacological Treatment for Claudication

• Cilostazol (100 mg orally 2 times per day) is
  indicated as an effective therapy to improve
  symptoms and increase walking distance in
  patients with lower extremity PAD and
  intermittent claudication (in the absence of
  heart failure).

A
Pentoxifylline (400 mg 3 times per day) may be
considered as second-line alternative therapy to
cilostazol to improve walking distance in
patients with intermittent claudication.
A
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
37
Lower-Extremity Occlusive Disease

• Catheter-based
• Revascularization
• Angioplasty (balloon, subintimal)
• Stents (stainless steel, nitinol)
• Covered stents (Dacron, PTFE)
• Rotational atherectomy
• Other interventions (cryoplasty, brachytherapy)

• Surgical
• Reconstruction
• Aortic bifemoral bypass
• Infrainguinal bypass (vein, PTFE)

38
Indications for Revascularization

• Lifestyle-interfering intermittent claudication
• Limb-threatening ischemia
• Ischemic rest pain
• Nonhealing ulceration
• Gangrene

39
ACC/AHA 2006 PAD Management GuidelinesEndovascula
r Intervention of Intermittent Claudication

• Endovascular procedures are indicated for
  individuals with a vocational or
  lifestyle-limiting disability due to
  intermittent claudication when clinical features
  suggest a reasonable likelihood of symptomatic
  improvement with endovascular intervention and
  (a) there has been an inadequate response to
  exercise or pharmacological therapy and/or (b)
  there is a very favorable risk-benefit ratio (eg,
  focal aortoiliac occlusive disease).

A
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
40
ACC/AHA 2006 PAD Management GuidelinesThrombolysi
s for Acute and Chronic Limb Ischemia

• Catheter-based thrombolysis is an effective and
  beneficial therapy and is indicated for patients
  with acute limb ischemia (Rutherford categories 1
  and IIa) of less than 14 days duration.

A
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
41
ACC/AHA 2006 PAD Management GuidelinesCritical
Limb Ischemia and Treatment for Limb Salvage

• Parenteral administration of prostaglandin E-1
  (PGE-1) or iloprost for 7 to 28 days may be
  considered to reduce ischemic pain and facilitate
  ulcer healing in patients with CLI, but its
  efficacy is likely to be limited to a small
  percentage of patients.

A
Adapted from Hirsch AT, et al. Available at
http//www.acc.org/clinical/guidelines/pad/summary
.pdf.
42
Featured Institution Maricopa Medical
Center Phoenix, Arizona
43
Polling Question 2
If you participated in a previous teleconference,
how much progress have you made since
then? (Please refer to the checklists on the next
3 slides.)

• We are currently on the same item
• We have since moved to the next checkbox on the
  checklist
• We have progressed by more than one item on the
  checklist
• ACS pathways are up-to-date and regularly
  followed

44
Progress ChecklistImmediate Goals
45
Progress ChecklistShort-term Goals/Activities
46
Progress ChecklistLong-term Goals/Activities
47
Question-and-Answer Session
48
Concluding RemarksChristopher P. Cannon,
MDNext Program Highlights From the American
College of Cardiology 2006 Annual Scientific
SessionGregg C. Fonarow, MDWednesday, March
22, 2006300 PM Eastern Time (1200 Noon
Pacific Time)