Practical Considerations in Chronic Ischemic Heart Disease Management

1
Practical Considerations in Chronic Ischemic
Heart Disease Management
2
Angina treatment Objectives

• Reduce ischemia and relieve anginal symptoms
• Improve quality of life
• Prevent MI and death
• Improve quantity of life

Gibbons RJ et al. ACC/AHA 2002 guidelines.
www.acc.org/clinical/guidelines/stable/stable.pdf

3
Comprehensive management of myocardial ischemia
Symptom management
Aggressive risk factor reduction
Antiplatelet therapy
Lifestyle modification
4
CAD Treatment challenges
5
ACC/AHA guidelines Chest pain evaluation
Contraindications to stress testing
Yes
Consider angiography
No
Symptoms/clinical findings warrant angiography
Yes
No
Low/intermediate risk
No
Pharmacologic imaging study
Patient able to exercise
Yes
Treatment
Previous coronary revascularization
Yes
Exercise imaging study
No
High risk
Consider angiography
Resting ECG interpretable
No
Consider angiography/revascularization
Yes
High risk
Exercise test
Consider imaging study/angiography
Treatment
Gibbons RJ et al. ACC/AHA 2002 guidelines. www.acc
.org/clinical/guidelines/stable/stable.pdf.
If adequate information on diagnosis/prognosis
available
6
ACC/AHA guidelines Chronic stable angina
treatment
Sublingual NTG
Patient education
CCB,Long-acting nitrate
Yes
Prinzmetal angina?
Medications/conditions that provoke/exacerbate
angina?
Yes
Treat appropriately
No
ß-blocker
Routine follow-up
Serious contraindication or unsuccessful
treatment
Add/substitute CCB
Consider revascularization
Serious contraindication or unsuccessful
treatment
Add long-acting nitrate
Gibbons RJ et al. ACC/AHA 2002 guidelines. www.acc
.org/clinical/guidelines/stable/stable.pdf.
Unsuccessful treatment
7
Substantial growth in PCI
5 national sample of Medicare beneficiaries
Adapted from Lucas FL et al. Circulation.
2006113374-9.
Adjusted for age, gender, race
8
Stable CAD PCI vs conservative medical management
Meta-analysis of 11 randomized trials N 2950
Favors medical management
Favors PCI
0
1
2
Risk ratio(95 Cl)
Katritsis DG et al. Circulation. 20051112906-12.
9
Major benefit of PCI Angina symptom relief
N 1020 undergoing elective PCI 1 year follow-up
Patients ()
Spertus JA et al. Circulation. 20041103789-94.
Seattle Angina Questionnaire
10
CAD progression Major cause of
post-revascularization angina
5-year follow-up
P 0.26
65
70
55
60
50
P 0.35
40
Patients
P 0.67
27
()
30
20
18
20
14
10
0
Initially treated
Untreated
Treated and
vessels only
vessels only
untreated vessels
PCI
CABG
Alderman EL et al. J Am Coll Cardiol.
200444766-74.
11
Conditions limiting repeat revascularization

• Advanced age
• Impaired LV function
• Multiple prior revascularizations
• Lack of suitable conduits for revascularization
• Diffuse disease and/or poor distal target vessels
  (eg, persons with diabetes)
• Comorbid conditions that ? risk of
  perioperative/postoperative complications

Mannheimer C et al. Eur Heart J. 200223355-70.
12
Diabetes and PCI Factors influencing outcome
Inflammation
Prothrombotic state
CAD progression and/or worse outcomes post PCI
Restenosis
Endothelial dysfunction
Renal dysfunction LV dysfunction PAD
Atherosclerotic burden
Roffi M and Topol EJ. Eur Heart J. 200425190-8.
13
CARISA Ranolazine benefits patients with and
without diabetes

Placebo
Ranolazine SR750 mg bid
Ranolazine SR1000 mg bid
Timmis AD et al. Eur Heart J. 20062742-8.
Pinteraction 0.81
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CARISA Ranolazine reduces A1C
N 189 with diabetes on background antianginal
therapy

• Possible mechanisms include
• Improved insulin sensitivity
• Increased physical activity

P 0.008
P 0.0002
Cooper-DeHoff R and Pepine CJ. Eur Heart J.
2006275-6.Timmis AD et al. Eur Heart J.
20062742-8.
R ranolazine SRn 31/189 also receiving
insulin
15
Selective vs routine catheterization Cost
reduction
N 11,249 consecutive stable angina patients
Myocardial perfusion plus selective cath
Routine early cath
Pretest clinical risk
Shaw LJ et al. J Am Coll Cardiol. 199933661-9.
Includes diagnostic and follow-up costs
16
Chronic stable angina Pharmacotherapy
ACC/AHA guidelines
Aspirin ß-blockers in patients with prior
MI ß-blockers in patients without prior
MI Lipid-lowering therapy in patients with
suspected CAD and LDL-C gt130 mg/dL (target LDL-C
lt100 mg/dL) ACEI in all patients with CAD who
have diabetes and/or LV systolic dysfunction
Gibbons RJ et al. ACC/AHA 2002 guidelines. www.acc
.org/clinical/guidelines/stable/stable.pdf.Grundy
SM et al. Circulation. 2004110227-39.
Optional goal of lt70 mg/dL in patients at very
high risk (ATP III Update)
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CRUSADE Nonpharmacologic interventions at
discharge
N 35,897 patients with UA/NSTEMI Oct 2004Sept
2005


Patients ()


CRUSADE. www.crusadeqi.com
Can Rapid risk stratification of Unstable angina
patients Suppress ADverse outcomes with Early
implementation of the ACC/AHA guidelines
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CRUSADE Discharge medications following UA/NSTEMI
N 35,897 patients without contraindications
Patients ()
CRUSADE. www.crusadeqi.com
Oct 2004Sept 2005
19
How important is IHD in women?

• Leading cause of death
• Mostly due to IHD and stroke
• More common cause of death than cancer
• Compared to men
• Present at older age
• Less likely to be diagnosed and treated
• Higher CVD mortality
• Estimated annual cost gt400 billion

Problem will increase as population ages and
epidemics of obesity, metabolic syndrome, and
diabetes continue
AHA. http//www.americanheart.org/downloadable/hea
rt/1136818052118Females06.pdf.Pepine CJ. J Am
Coll Cardiol. 2004431727-30.
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AHA guidelines Chest pain evaluation in women
Diabetes, abnormal rest ECG, questionable
exercise capacity
Normal rest ECG, able to exercise
Intermediate risk
Stress cardiac imaging
Exercise treadmill test
Able to exercise or symptoms with low-level
exercise
Low risk
Unable to exercise
Exercise stress
Pharmacologic stress
Moderately/severely abnormal test Reduced LVEF
Normal or mildly abnormal testNormal LVEF
Risk factor modification anti-ischemic Rx
Cardiac catheterization
Mieres JH et al. Circulation. 2005111682-96.
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IHD vasculopathy Gender differences

• Structural features (macro- and microvessels)
• Smaller size
• Increased stiffness (fibrosis, remodeling, etc)
• More diffuse disease
• More plaque erosion vs rupture
• Rarefaction (drop out), disarray, microemboli,
  etc
• Functional features (macro- and microvessels)
• Endothelial dysfunction
• Smooth muscle dysfunction (Raynauds, migraine,
  CAS)
• Vasculitis (Takayasus, rheumatoid, SLE, CNSV,
  giant cell, etc)

CAS coronary artery spasm SLE systemic lupus
erythematosis CNSV central nervous system
vasculitis
Pepine CJ et al. J Am Coll Cardiol. 20064730S-5.
22
Ischemia in women Microvascular dysfunction

• Diminished coronary flow reserve
• Microvascular dysfunction exists in 50 of
  women presenting with chest pain and normal or
  near-normal coronary angiograms who had flow
  reserve measured

Reis SE et al. J Am Coll Cardiol.
1999331469-75. Reis SE et al. Am Heart J.
2001141735-41. Pepine CJ et al. J Am Coll
Cardiol. 20064730S-5.
Womens Ischemia Syndrome Evaluation (WISE) study
cohorts
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Less obstructive CAD Women vs men
Patients undergoing elective diagnostic
angiography for angina
Women
Men
ACC-National Cardiovascular Data Registry. J Am
Coll Cardiol. 2006.
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Women have more adverse outcomes vs men
Angina 2x ? morbidity/mortality
MI 1.5x ? 1-year mortality
CABG 2x ? morbidity/mortality
CAD
Heart failure 2x ? incidence
Pepine CJ. J Am Coll Cardiol. 2004431727-30.
25
Higher incidence of major CV events in women
Euro Heart Survey of Stable Angina n 1547
women, n 2478 men
Overall angina population
Women
Men
Angina with angiographic CAD
Women
Incidence ()
Men
Daly C et al. Circulation. 2006113490-8.
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Increased risk of death/MI in women with CAD
Euro Heart Survey of Stable Angina n 718 men,
n 276 women with angiographic CAD
Log rank P 0.02
Cumulative event probability
0
3
6
9
12
15
18
Time since entry (months)
Men
Women
Daly C et al. Circulation. 2006113490-8.
27
CRUSADE Gender and discharge medications
N 35,897 patients with UA/NSTEMI
100
80
60
Patients ()
40
20
0
Aspirin
?-blocker
ACEI
Statin
Clopidogrel
Discharge medications
Men
Women
Oct 2004Sept 2005 P values not reported
CRUSADE. www.crusadeqi.com
28
Euro Heart Survey Undertreatment of women
Euro Heart Survey of Stable Angina n 1582
women, n 2197 men
100


80
60


Patients ()
40
20
0
Antiplatelet
ASA
Lipid-
Statin
?-blocker
lowering
Men
Women
P lt 0.001
Daly C et al. Circulation. 2006113490-8.