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Practical Considerations in Chronic Ischemic Heart Disease Management. Angina treatment: Objectives. Reduce ischemia and relieve anginal symptoms Improve quality of life Prevent MI and death Improve quantity of life. - PowerPoint PPT Presentation
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Practical Considerations in Chronic Ischemic Heart Disease Management
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
Symptom management
Aggressive risk factor reduction
Lifestyle modification
Antiplatelet therapy
Comprehensive management of myocardial ischemia
CAD: Treatment challenges
Older antianginals Many patients cannot tolerate combinations at maximal doses
Disease-modifying agents BP, lipid, and glucose goals are being revised downward
PCI Many patients are not suitable candidates
Lifestyle modification Noncompliance limits long-term benefit
ACC/AHA guidelines: Chest pain evaluationContraindications to
stress testing
Symptoms/clinical findings warrant angiography
Patient able to exercise
Previous coronary revascularization
Resting ECG interpretable
Gibbons RJ et al. ACC/AHA 2002 guidelines.www.acc.org/clinical/guidelines/stable/stable.pdf.
Low/intermediate risk
*If adequate information on diagnosis/prognosis available
Yes
No
Yes
NoNo
Yes
Yes
No
No
YesHigh risk
High risk
Exercise test
Treatment*
Consider imaging study/angiography
Consider angiography/revascularization
Exercise imaging study
Pharmacologic imaging study
Consider angiography
Consider angiography
Treatment*
ACC/AHA guidelines: Chronic stable angina treatment
Sublingual NTG
Prinzmetal angina? CCB,Long-acting nitrate
Medications/conditions that provoke/exacerbate angina?
β-blocker
Patient education
Gibbons RJ et al. ACC/AHA 2002 guidelines.www.acc.org/clinical/guidelines/stable/stable.pdf.
Treat appropriately
Routine follow-up
Consider revascularizationSerious contraindication or unsuccessful treatment
Yes
Yes
Unsuccessful treatment
No
Serious contraindication or unsuccessful treatment
Add/substitute CCB
Add long-acting nitrate
Substantial growth in PCI
19%
69%
115%
0
25
50
75
100
125
CABG Cardiaccatheterization
PCI
Increase from 1993-2001*
Adapted from Lucas FL et al. Circulation. 2006;113:374-9.
5% national sample of Medicare beneficiaries
*Adjusted for age, gender, race
Meta-analysis of 11 randomized trials; N = 2950
Stable CAD: PCI vs conservative medical management
Death
Cardiac death or MI
Nonfatal MI
CABG
PCI
Katritsis DG et al. Circulation. 2005;111:2906-12.
0 1 2
P
0.68
0.28
0.12
0.82
0.34
Risk ratio(95% Cl)
Favors PCIFavors medical
management
Major benefit of PCI: Angina symptom relief
51
17 1912 13
72
0
10
20
30
40
50
60
70
80
No change Moderate improvement Large improvement
Change in QOL scoreAngina absent Angina present
Spertus JA et al. Circulation. 2004;110:3789-94.
N = 1020 undergoing elective PCI; 1 year follow-up
Patients(%)
Seattle Angina Questionnaire
CAD progression: Major cause of post-revascularization angina
Alderman EL et al. J Am Coll Cardiol. 2004;44:766-74.
P = 0.35
P = 0.26
P = 0.67
5-year follow-up
20
65
14
27
55
18
0
10
20
30
40
50
60
70
Initially treatedvessels only
Untreated Treated anduntreated vessels
Patients (%)
PCI CABG
vessels only
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. 2002;23:355-70.
Diabetes and PCI: Factors influencing outcome
Roffi M and Topol EJ. Eur Heart J. 2004;25:190-8.
CAD progression and/or worse
outcomes post PCI
InflammationProthrombotic
state
Renal dysfunctionLV dysfunction
PAD
Atherosclerotic burden
RestenosisEndothelial dysfunction
CARISA: Ranolazine benefits patients with and without diabetes
3.03.4
2.1
2.6
1.0
2.5
0
1
2
3
4
Diabetes (n = 189) No diabetes (n = 634)
Mean anginalepisodes/
week
Timmis AD et al. Eur Heart J. 2006;27:42-8.
Placebo Ranolazine SR750 mg bid
Ranolazine SR1000 mg bid
Pinteraction = 0.81
CARISA: Ranolazine reduces A1C
• Possible mechanisms include:– Improved insulin
sensitivity– Increased physical
activity
A1C change from baseline
-0.02
-0.5
-0.72-0.8
-0.6
-0.4
-0.2
0
ΔA1C(%)
Placebo R 750 mg bid R 1000 mg bid
Cooper-DeHoff R and Pepine CJ. Eur Heart J. 2006;27:5-6.Timmis AD et al. Eur Heart J. 2006;27:42-8.
R = ranolazine SRn = 31/189 also receiving insulin
N = 189 with diabetes on background antianginal therapy
P = 0.008
P = 0.0002
Selective vs routine catheterization: Cost reduction
2.9
4.2
4.8
2.02.4
2.8
0
1
2
3
4
5
6
Low Intermediate High Low Intermediate High
Cost (thousands
of $)*
Shaw LJ et al. J Am Coll Cardiol. 1999;33:661-9.
Pretest clinical risk
N = 11,249 consecutive stable angina patientsMyocardial perfusion plus
selective cathRoutine early cath
*Includes diagnostic and follow-up costs
Chronic stable angina: Pharmacotherapy
ACC/AHA guidelines
Gibbons RJ et al. ACC/AHA 2002 guidelines.www.acc.org/clinical/guidelines/stable/stable.pdf.
Grundy SM et al. Circulation. 2004;110:227-39.*Optional goal of <70 mg/dL in patients at very high risk (ATP III Update)
II IIaIIa IIbIIb IIIIIIAspirin
β-blockers in patients with prior MI
β-blockers in patients without prior MI
Lipid-lowering therapy in patients with suspected CAD and LDL-C >130 mg/dL (target LDL-C <100 mg/dL*)
ACEI in all patients with CAD who have diabetes and/or LV systolic dysfunction
CRUSADE: Nonpharmacologic interventions at discharge
67
82
65
85
0
20
40
60
80
100
Lipid paneldrawn
Dietarycounseling
Cardiac rehabreferral
Smokingcessation
counseling
N = 35,897 patients with UA/NSTEMI; Oct 2004–Sept 2005
CRUSADE. www.crusadeqi.com
Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines
Patients (%)
CRUSADE: Discharge medications following UA/NSTEMI
94 92
65
88
73
0
20
40
60
80
100
ASA β-blocker ACEI Any lipid-lowering
agent
Clopidogrel
N = 35,897 patients without contraindications
CRUSADE. www.crusadeqi.com
Patients (%)
Oct 2004–Sept 2005
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: >$400 billion
AHA. http://www.americanheart.org/downloadable/heart/1136818052118Females06.pdf.Pepine CJ. J Am Coll Cardiol. 2004;43:1727-30.
Problem will increase as population ages and epidemics of obesity, metabolic syndrome, and diabetes continue
AHA guidelines: Chest pain evaluation in women
Mieres JH et al. Circulation. 2005;111:682-96.
Normal rest ECG, able to exercise
Diabetes, abnormal rest ECG, questionable exercise capacity
Stress cardiac imaging
Risk factor modification ± anti-ischemic Rx
Low risk
Intermediate risk
Able to exercise or symptoms with low-level exercise Unable to exercise
Exercise stress Pharmacologic stress
Cardiac catheterization
Normal or mildly abnormal testNormal LVEF
Moderately/severely abnormal test Reduced LVEF
Exercise treadmill test
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 (Raynaud’s, migraine, CAS)
• Vasculitis (Takayasu’s, rheumatoid, SLE, CNSV, giant cell, etc)
IHD vasculopathy: Gender differences
Pepine CJ et al. J Am Coll Cardiol. 2006;47:30S-5.
CAS = coronary artery spasmSLE = systemic lupus erythematosis CNSV = central nervous system vasculitis
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. 1999;33:1469-75.Reis SE et al. Am Heart J. 2001;141:735-41.
Pepine CJ et al. J Am Coll Cardiol. 2006;47:30S-5.Women’s Ischemia Syndrome Evaluation (WISE) study cohorts
Less obstructive CAD: Women vs men
0
20
40
60
80
100
<40 40-49 50-59 60-69 70-79 >79
Age (years)
Patients with >50% stenosis
(%)
Patients undergoing elective diagnostic angiography for angina
Women Men
ACC-National Cardiovascular Data Registry™. J Am Coll Cardiol. 2006.
Women have more adverse outcomes vs men
Pepine CJ. J Am Coll Cardiol. 2004;43:1727-30.
Angina~2x morbidity/mortality
Heart failure~2x incidence
MI~1.5x 1-year mortality
CABG~2x morbidity/mortality
CAD
Higher incidence of major CV events in women
0
2
4
6
8
10
12
14
Death Nonfatal MI HF Unstableangina
Emergencyrevasc
Overall angina population
Angina with angiographic CAD
Women
Women
Men
Men
Euro Heart Survey of Stable Angina; n = 1547 women, n = 2478 men
Daly C et al. Circulation. 2006;113:490-8.
Incidence (%)
Daly C et al. Circulation. 2006;113:490-8.
Euro Heart Survey of Stable Angina; n = 718 men, n = 276 women with angiographic CAD
Increased risk of death/MI in women with CAD
Cumulative event
probability
Time since entry (months)
0.15
0.10
0.05
0
0 3 6 9 12 15 18
Log rank: P = 0.02
Men Women
CRUSADE: Gender and discharge medications
N = 35,897 patients with UA/NSTEMI
CRUSADE. www.crusadeqi.com
Patients (%)
MenWomen
Oct 2004–Sept 2005P values not reported
0
20
40
60
80
100
Aspirin -blocker ACEI Statin Clopidogrel
Discharge medications
Euro Heart Survey: Undertreatment of women
*P < 0.001
* *
* *
Daly C et al. Circulation. 2006;113:490-8.
Euro Heart Survey of Stable Angina; n = 1582 women, n = 2197 men
Patients (%)
MenWomen
0
20
40
60
80
100
Antiplatelet ASA Lipid-lowering
Statin -blocker