Transcript ACC/AHA PAD Guideline Slide Set

Treatment
Two Major Goals in Treating Patients With PAD
Cardiovascular
morbidity and mortality
outcomes
Limb outcomes
• Improved ability to walk
– Increase in peak walking
distance
– Improvement in qualityof-life (QoL)
• Prevention of progression
to CLI and amputation
•
•
Decrease in morbidity from
non-fatal MI and stroke
Decrease in cardiovascular
mortality from fatal MI and
stroke
Treatment to Improve
Cardiovascular Outcomes
Effect of Smoking Cessation on Survival
133 Patients observed after bypass graft or lumbar sympathectomy
Cumulative Survival (%)
100
80
60
40
Australian census
Tobacco abstinence
Continued tobacco use
20
0
0
1
2
3
4
5
Years Postoperative
Faulkner KW, et al. Med J Aust. 1983;1:217-219.
Smoking Cessation Therapy
I IIa IIb III
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.
Heart Protection Study:
Vascular Event by Prior Disease
Incidence of events
Statin
Existing disease
Control
(n=10,269) (n=10,267)
Previous MI
23.5
29.4
Other CHD
18.9
24.2
No prior CHD or CBV disease 18.7
23.6
PAD
24.7
30.5
Diabetes
13.8
18.6
All patients
19.8
25.2
Risk vs Control
Statin favored Placebo
24% Reduction
(P<.0001)
0.4 0.6 0.8
1.0 1.2 1.4
CBD=cerebrovascular disease; CHD=congestive heart disease. Reprinted with permission from Heart Protection
Study Collaborative Group. Lancet. 2002;360:7-22 from Elsevier.
Atorvastatin in Patients
With Claudication and PAD
Mean change from baseline
in PFWT (sec)
125
100
10 mg
80 mg
Placebo
*
75
50
25
0
Baseline
Month 3
Month 6
Month 12
PFWT=pain-free walking time.
*P=.03. No change in ABI over 12 months.
Reprinted with permission from Mohler ER et al. Circulation. 2003;108:1481-1486.
Considerations for the Treatment of
Hypertension in PAD
• Blood pressure lowering is indicated to reduce
the risk of stroke, MI, CHF, CRF, and death.
• Only major reductions in perfusion pressure may
worsen claudication (21 mm Hg decrease in SBP
resulted in a 9% decrease in absolute
claudication distance).
• Individuals with PAD should receive hypertension
treatment according to current national
guidelines (e.g., JNC-7).
CRF=chronic renal failure; CHF=congestive heart failure.
b- Blockers Are Not
Contraindicated in PAD
• In a meta analysis of 11 randomized
controlled trials beta-blocker therapy did not
worsen claudication in patients with PAD.
• Beta blockers had no significant effect on
pain-free walking distance compared with
placebo in pooled analysis.
Radack K. Arch Intern Med. 1991;151:1769.
Odds of MI, Stroke
or Vascular Death
Intensive Antihypertensive Therapy in
PAD: The ABCD Trial
40
Moderate treatment n = 227
Intensive treatment n = 227
*enalapril or nisoldipine
30
20
10
0
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3
Baseline ABI
Reprinted with permission from Mehler, et al. Circulation. 2003;107;753-756.
HOPE: Benefits in CV Risk Subgroups
Relative risk in ramipril group
No. of
Patients
History of CAD
No history of CAD
7477
1820
Prior MI
No prior MI
4892
4405
CBV disease
No CBV disease
1013
8284
Peripheral vascular disease
No peripheral vascular disease
4051
5246
Microalbuminuria
No microalbuminuria
1956
7341
Reduced Increased
0.6
0.8
1.0
1.2
CAD=coronary artery disease; CBV=cerebrovascular disease; MI=myocardial infarction.
Adapted with permission. HOPE Study Investigators. N Engl J Med. 2000;342:145-153. Copyright © 2000 Massachusetts Medical Society. All rights reserved.
PAD Guideline: Risk-factor Management
with Antihypertensive Medications
I IIa IIb III
I IIa IIb III
• Target BP < 140/90 mm Hg to reduce
cardiovascular/cerebrovascular risk in all
individuals with PAD
• If comorbid diabetes or chronic renal disease is
present, target BP < 130/80 mm Hg
I IIa IIb III
• b- Blockers are effective and not
contraindicated
I IIa IIb III
• Consider ACE inhibitors:
 For patients with symptomatic PAD
I IIa IIb III
 For patients with asymptomatic PAD
ACE=angiotensin-converting enzyme.
Hirsch AT et al. J Am Col Cardiol. 2006;47:1239-1312.
Antihypertensive Therapy
I IIa IIb III
I IIa IIb III
Antihypertensive therapy should be
administered to hypertensive patients with
lower extremity PAD to a goal of less than
140/90 mm Hg (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.
Beta-adrenergic blocking drugs are
effective antihypertensive agents and are
not contraindicated in patients with PAD.
Lipid Lowering Therapy
I IIa IIb III
I IIa IIb III
Treatment with a 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.
Treatment with a HMG coenzyme-A reductase
inhibitor (statin) medication to achieve a target
LDL cholesterol level of less than 70 mg per dl
is reasonable for patients with lower extremity
PAD at very high risk of ischemic events†.
† Factors that define “very high risk” in individuals with established PAD are: (a) multiple major risk factors (especially
diabetes), (b) severe and poorly controlled risk factors (especially continued cigarette smoking), (c) multiple risk factors
of the metabolic syndrome and (d) individuals with acute coronary syndromes.
HMG coenzyme=3-hydroxy-3-methylglutaryl coenzyme
UKPDS:
Intensive Blood-Glucose vs. Conventional Treatment
in Patients With Type 2 Diabetes
Favors
Conventional
Favors
Intensive
Clinical End Point
RR (95% CI)
0.1
1
10 Log-rank
p-value
Any diabetes-related end point
0.88 (0.79–0.99)
0.029
Diabetes-related deaths
0.90 (0.73–1.11)
0.34
All-cause mortality
0.94 (0.80–1.10)
0.44
MI
0.84 (0.71–1.00)
0.052
Stroke
1.11 (0.81–1.51)
0.52
Amputation or death from PAD
0.65 (0.36–1.18)
0.15
Microvascular disease
0.75 (0.60–0.93)
0.0099
PAD=peripheral arterial disease; RR=relative risk.
Reprinted with permission from UKPDS Group. Lancet. 1998;352:837-853 from Elsevier.
Diabetes Control and Complications Trial (DCCT):
Cumulative Incidence of the First of Any of the
Predefined Cardiovascular Disease Outcomes
The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research
Group. N Engl J Med. 2005;353:2643-2653. Copyright © 2005 Massachusetts Medical Society. All rights reserved.
PROactive:
All-Cause Mortality, MI, ACS, Coronary or Peripheral
Revascularization, Amputation, Stroke
Proportion of Events (%)
25
10% Relative
risk reduction
20
HR* 0.90 (0.80–1.02)
P = 0.095
Placebo
(572 events)
Pioglitazone
(514 events)
15
10
5
0
0
6
Number at risk
Pioglitazone
Placebo
*Unadjusted
2488
2530
12
18
24
Time From Randomization
2373
2413
2302
2317
2218
2215
30
36
2146
2122
348
345
Reprinted with permission from Dormandy JA, et al. Lancet. 2005;366:1279-89.
PROactive: Secondary Outcome
All-cause mortality, MI (excluding silent MI), stroke
25
Proportion of Events (%)
20
Placebo
(358 events)
16% Relative
risk reduction
15
HR* 0.84 (0.72–0.98)
P = 0.027
10
Pioglitazone
(301 events)
5
0
0
6
Number at risk
12
18
24
Time From Randomization
30
36
Pioglitazone
2536
2487
2435
2381
2336
396
Placebo
2566
2504
2442
2371
2315
390
*Unadjusted
Reprinted with permission from Dormandy JA et al. Lancet. 2005;366:1279-89.
PAD Care Standards for Patients
With Diabetes
I IIa IIb III
I IIa IIb III
Proper foot care, including use of appropriate
footwear, chiropody/podiatric medicine, daily
foot inspection, skin cleansing, and use of
topical moisturizing creams, should be
encouraged and skin lesions and ulcerations
should be addressed urgently in all diabetic
patients with lower extremity PAD.
Treatment of diabetes in individuals with lower
extremity PAD by administration of glucose
control therapies to reduce the hemoglobin
HbA1C to less than 7% can be effective to
reduce microvascular complications and
potentially improve cardiovascular outcomes.
Mechanisms of Action of Oral
Antiplatelet Therapies
ASA=aspirin; COX=cyclooxygenase; PDE=phosphodiesterase.
Schafer AI. Am J Med. 1996;101:199-209.
Antiplatelet Trialists’ Collaboration:
Patients Having
MI, Stroke, or Vascular Death (%)
Efficacy of Antiplatelet Therapy in Prevention of Ischemic Events
25
22
Odds Reduction
All antiplatelet therapy
control
25
20
29
27
15
25
32
10
5
0
Prior
stroke/TIA
Acute
MI
Prior
MI
Other
All high- All trials
high risk*
risk (high or low)
trials
*Other high-risk patients include: unstable/stable angina, post-CABG, PAD, and diabetic patients.
CABG=coronary artery bypass graft; PAD=peripheral arterial disease; TIA=transient ischemic attack.
Antiplatelet Trialists’ Collaboration. Brit Med J. 1994;308:81-106.
Antithrombotic Trialists’ Collaboration (ATC):
Meta-Analysis of Vascular Events in Antiplatelet Trials in Patients With PAD
Category
APT
CTRL
Reduction (%)
Intermittent
claudication
6.4%
7.9%
23±9
Peripheral artery
bypass graft
5.4%
6.5%
22±16
Peripheral
angioplasty
2.5%
3.6%
29±35
All high-risk patients
22±2
(P<.001)
0.0
0.5
1.0
1.5
2.0
N=9214.
Data from 197 randomized trials comparing an antiplatelet agent (APT; aspirin, clopidogrel,
dipyridamole, or a glycoprotein IIb/IIIa antagonist) vs control or another antiplatelet agent.
APT=antiplatelet; CRTL=control.
Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86.
Risk of Occlusive Vascular Events in High-Risk
Patients: Antithrombotic Trialists’ Collaboration
Risk category
(No. of trials
with data)
Patients with event (%)
APT
Control
6.4
7.9
Peripheral
grafting (n=12)
5.4
6.5
Peripheral
angioplasty (n=4)
2.5
3.6
All PAD trials (n=42)
5.8
7.1
IC (n=26)
Risk vs control
Reduced
Reduced Increased
N=9706
0.0
0.5
1.0
1.5
2.0
APT=antiplatelet therapy with aspirin, clopidogrel, dipyridamide, or a glycoprotein IIb/IIIa antagonist; IC=intermittent claudication.
Reprinted with permission Antithrombotic Trialists’ Collaboration. Brit Med J. 2002;324:71-86.
Efficacy of Clopidogrel vs. Aspirin in MI,
Ischemic Stroke, or Vascular Death
8.7%*
Overall
Relative Risk
Reduction
Cumulative
Event Rate (%)
16
ASA
12
5.83%
8
5.32%
Clopidogrel
4
0
0
3
6
9 12 15 18 21 24 27 30 33 36
N=19,185
Months of Follow-Up
ASA=aspirin.
Mean follow-up=1.91 years.
*ITT analysis.
Reprinted with permission from CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.
Risk Reduction of Clopidogrel vs. Aspirin in
Patients With Atherosclerotic Vascular Disease
Clopidogrel favored
Aspirin favored
N=19,185
Stroke
MI
PAD
All patients
-30
-20
-10
0
10
20
30
40
Reprinted with permission from CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.
CHARISMA: Affect of Clopidogrel Plus Aspirin
vs. Aspirin Alone on MI, Stroke, or CV Death
First occurrence of MI (fatal or nonfatal),
stroke (fatal or nonfatal), or CV death†
Cumulative Event Rate* (%)
8
Placebo + ASA
7.3%
Clopidogrel + ASA
6.8%
6
4
RRR 7.1% (95% CI: -4.5%, 17.5%)
P=0.22
2
0
0
6
12
18
24
30
Months Since Randomization§
ASA=aspirin; CI=confidence interval; MI=myocardial infarction; RRR=relative risk ratio. *All patients received ASA 75-162 mg/day; †The number of patients followed
beyond 30 months decreases rapidly to zero; only 21 primary efficacy events occurred beyond this time (13 clopidogrel and 8 placebo).
Bhatt DL, Fox KA, Hacke W, et al. N Engl J Med 2006;354:1706.
CHARISMA: Primary Efficacy Results
(MI/Stroke/CV Death) by Pre-Specified Entry Category
Population
RRR (95% CI)
P
Qualifying CAD, CVD, or PAD
(n=12,153)
0.88 (0.77, 0.998)
0.046
Multiple risk factors
(n=3,284)
1.20 (0.91, 1.59)
0.20
Overall population*
(N=15,603)
0.93 (0.83, 1.05)
0.22
0.4 0.6 0.8
Clopidogrel better
1.2 1.4 1.6
Placebo better
CAD=coronary artery disease; CI=confidence interval; CVD=cardiovascular disease; MI=myocardial infarction; RRR=relative risk ratio.
*A statistical test for interaction showed marginally significant heterogeneity (P=0.045) in treatment response for these prespecified subgroups of patients.
Adapted from Bhatt DL, Fox KA, Hacke W, et al. N Engl J Med 2006;354:1706..
Antiplatelet Therapy
I IIa IIb III
I IIa IIb III
I IIa IIb III
Antiplatelet therapy is indicated to reduce the risk of
myocardial infarction, stroke, or vascular death in
individuals with atherosclerotic lower extremity PAD.
Aspirin, in daily doses of 75 to 325 mg, is
recommended as safe and effective antiplatelet
therapy to reduce the risk of myocardial infarction,
stroke, or vascular death in individuals with
atherosclerotic lower extremity PAD.
Clopidogrel (75 mg per day) is recommended as an
effective alternative antiplatelet therapy to aspirin to
reduce the risk of myocardial infarction, stroke, or
vascular death in individuals with atherosclerotic lower
extremity PAD.
Treatment of the Asymptomatic
Patient With PAD
I IIa IIb III
I IIa IIb III
• Smoking cessation, lipid lowering, and
diabetes and hypertension treatment
according to current national treatment
guidelines are recommended for individuals
with asymptomatic lower extremity PAD.
• Antiplatelet therapy is indicated for individuals
with asymptomatic lower extremity PAD to
reduce the risk of adverse cardiovascular
ischemic events.