82. Practical Considerations in Chronic Ischemic Heart Disease Management
Treatment goals in the patient with stable CAD include reduction in symptoms and prevention of MI and death.1
A multifactorial approach is required to attain these goals.
Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for the Management of Patients with Chronic Stable Angina) Available at

83. Angina treatment: Objectives
Reduce ischemia and relieve anginal symptoms
Improve quality of life
Prevent MI and death
Improve quantity of life
Angina treatment: Objectives
As outlined in the current guidelines, angina treatment is directed towards preventing MI and death (thereby improving the “quantity” of life) as well as preventing further ischemia and related symptoms (thereby improving quality of life).
Gibbons RJ et al. ACC/AHA 2002 guidelines.

84. Comprehensive management of myocardial ischemia
Symptom management
Aggressive risk factor reduction
Antiplatelet therapy
Comprehensive management of myocardial ischemia
Symptom control (through revascularization and/or medical therapy) represents only one arm of a treatment plan.
The second goal is prevention of MI and death, which will require addressing atherosclerotic disease throughout the coronary vasculature with lifestyle modification, aggressive risk factor reduction, and antiplatelet therapy.1
Lifestyle modification
Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the Guidelines for the Management of Patients with Chronic Stable Angina) Available at

85. 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
CAD: Treatment challenges
Clinicians have a number of effective treatment modalities available for managing patients with CAD.
However, each has its limitations and tailoring a regimen to the needs of a specific patient can present difficulties, particularly in the elderly and those with diabetes or heart failure. These patients frequently are not suitable candidates for revascularization, can only tolerate a modest exercise regimen, and have a relative intolerance to full doses of beta-blockers, calcium channel blockers, and nitrates.

86. 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
Patient able to exercise
Pharmacologic imaging study
Yes
Previous coronary revascularization
Yes
Treatment*
Exercise imaging study No
High risk
Consider angiography
Resting ECG interpretable No
ACC/AHA guidelines: Chest pain evaluation
Consider angiography/ revascularization
Yes
The current guidelines provide the algorithm above for use in diagnosis and risk stratification of patients with chest pain and moderate to high probability of CAD.
Ongoing trials such as Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) may provide insight into the role of newer imaging modalities.
High risk
Exercise test
Consider imaging study/ angiography
Treatment*
*If adequate information on diagnosis/prognosis available
Gibbons RJ et al. ACC/AHA 2002 guidelines.

87. ACC/AHA guidelines: Chronic stable angina treatment
Sublingual NTG
Patient education
Yes
CCB, Long-acting nitrate
Prinzmetal angina?
Medications/conditions that provoke/exacerbate angina?
Yes
Treat appropriately No
β-blocker
Routine follow-up
ACC/AHA guidelines: Chronic stable angina treatment
Serious contraindication or unsuccessful treatment
The 2002 guideline update on management of patients with chronic stable angina emphasized antianginal therapy over coronary revascularization, particularly in patients with single-vessel disease.
However, given the limitations of older antianginals and the advances in PCI, this algorithm is unlikely to reflect current clinical practice, and patients usually undergo PCI much sooner.
Add/substitute CCB
Serious contraindication or unsuccessful treatment
Consider revascularization
Add long-acting nitrate
Gibbons RJ et al. ACC/AHA 2002 guidelines.
Unsuccessful treatment

88. Substantial growth in PCI
5% national sample of Medicare beneficiaries
Substantial growth in PCI
Limitations of older anginal therapies as well as technical improvements in intervention procedures have led to increasing use of elective percutaneous coronary intervention (PCI) to treat stable coronary artery disease (CAD).
*Adjusted for age, gender, race
Adapted from Lucas FL et al. Circulation. 2006;113:374-9.

89. Stable CAD: PCI vs conservative medical management
Meta-analysis of 11 randomized trials; N = 2950
Favors medical management
Death
Cardiac death or MI
Nonfatal MI
CABG
PCI
Favors PCI P
0.68
0.28
0.12
0.82
0.34
Stable CAD: PCI vs conservative medical management
Katritsis et al conducted a meta-analysis of 11 randomized trials that compared PCI with conservative medical management in patients with chronic stable CAD.
While PCI effectively relieves angina, it does not offer any long-term advantage over medical management in terms of death, MI, or need for additional revascularization. 1 2
Risk ratio (95% Cl)
Katritsis DG et al. Circulation. 2005;111:

90. Major benefit of PCI: Angina symptom relief
N = 1020 undergoing elective PCI; 1 year follow-up
Patients
(%)
Major benefit of PCI: Angina symptom relief
Patients with stable CAD and angina are more likely to have improved QOL following PCI than those who have CAD but are free from angina.
In this study, the majority of patients with angina (72%) reported a large improvement in QOL following elective PCI. In contrast, only 19% of patients who were symptom-free reported a large improvement in QOL following elective PCI.
That is, the major benefit of PCI in stable CAD is angina relief.
Seattle Angina Questionnaire
Spertus JA et al. Circulation. 2004;110:

91. CAD progression: Major cause of post-revascularization angina
5-year follow-up
P = 0.26 70 65 60 55 50
P = 0.35
Patients 40
(%) 27
P = 0.67 30 20 18 20 14
CAD progression: Major cause of post-revascularization angina 10
CAD is a systemic process and patients frequently have plaques at sites other than the one responsible for exertional angina. CAD progression at these other sites is the major long-term cause of CV events following successful coronary revascularization.
Alderman et al demonstrated this in a 5-year follow-up of 407 patients who underwent PCI or CABG.
Initially treated
Untreated
Treated and
vessels only
vessels only
untreated vessels
PCI
CABG
Alderman EL et al. J Am Coll Cardiol. 2004;44:

92. 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
Conditions limiting repeat revascularization
PCI is not suitable for all patients.
These data were obtained in European populations, but are likely to be relevant to US patients.
Mannheimer C et al. Eur Heart J. 2002;23:

93. Diabetes and PCI: Factors influencing outcome
Inflammation
Prothrombotic state
CAD progression and/or worse outcomes post PCI
Endothelial dysfunction
Restenosis
Diabetes and PCI: Factors influencing outcome
Renal dysfunction
LV dysfunction
PAD
Atherosclerotic burden
The role of PCI in reducing chronic stable angina is less advantageous for persons with diabetes than for those without diabetes.
A more diffuse and extensive atherosclerosis develops in those with diabetes, which results in smaller vessels and a less suitable anatomy for PCI.
In those with diabetes who do undergo PCI, outcomes tend to be worse.
Roffi M and Topol EJ. Eur Heart J. 2004;25:190-8.

94. CARISA: Ranolazine benefits patients with and without diabetes
Subgroup analysis indicated a similar reduction in weekly anginal episodes in patients both with and without diabetes.
Placebo
Ranolazine SR 750 mg bid
Ranolazine SR 1000 mg bid
Pinteraction = 0.81
Timmis AD et al. Eur Heart J. 2006;27:42-8.

95. CARISA: Ranolazine reduces A1C
N = 189 with diabetes on background antianginal therapy
Possible mechanisms include:
Improved insulin sensitivity
Increased physical activity
CARISA: Ranolazine reduces A1C
P = 0.008
Both ranolazine SR doses significantly reduced A1C vs placebo.
The reduction in A1C was observed regardless of background insulin therapy.
The study investigators speculate that these findings may be due to improved insulin sensitivity with ranolazine SR or may be due to improved physical activity as a result of greater exercise tolerance and fewer anginal episodes.
Thus, ranolazine lacks the metabolic abnormalities associated with beta-blockers and is suitable for use in patients with diabetes.
P =
R = ranolazine SR n = 31/189 also receiving insulin
Cooper-DeHoff R and Pepine CJ. Eur Heart J. 2006;27:5-6. Timmis AD et al. Eur Heart J. 2006;27:42-8.

96. Selective vs routine catheterization: Cost reduction
N = 11,249 consecutive stable angina patients
Myocardial perfusion plus selective cath
Routine early cath
Selective vs routine catheterization: Cost reduction
Shaw et al conducted a prospective observational study of 5,423 patients who were referred for direct cardiac catheterization and 5,826 patients who were referred for risk stratification via myocardial perfusion tomography with selective catheterization.
Their assessment revealed that the more aggressive intervention strategy was associated with higher costs, principally because of a greater number of catheterization procedures.
Pretest clinical risk
*Includes diagnostic and follow-up costs
Shaw LJ et al. J Am Coll Cardiol. 1999;33:661-9.

97. Chronic stable angina: Pharmacotherapy
ACC/AHA guidelines I
IIa
IIb
III
Aspirin
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
Chronic stable angina: Pharmacotherapy
The ACC/AHA 2002 guideline update for the management of patients with chronic stable angina recommends antiplatelet therapy (principally aspirin), beta-blockers, lipid-lowering therapy (principally statins), and ACE inhibitors to prevent MI and death.
Gibbons RJ et al. ACC/AHA 2002 guidelines.
Grundy SM et al. Circulation. 2004;110:
*Optional goal of <70 mg/dL in patients at very high risk (ATP III Update)

98. CRUSADE: Nonpharmacologic interventions at discharge
N = 35,897 patients with UA/NSTEMI; Oct 2004–Sept 2005
Patients (%)
CRUSADE: Nonpharmacologic interventions at discharge
CRUSADE results obtained from October 2004 to September 2005 show opportunities for improvement in drawing lipid panels and referring patients for dietary and smoking cessation counseling, and for cardiac rehabilitation.
Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines
CRUSADE.

99. CRUSADE: Discharge medications following UA/NSTEMI
N = 35,897 patients without contraindications
Patients (%)
CRUSADE: Discharge medications following UA/NSTEMI
Use of beta-blockers, effective antianginal medications, is high.
Oct 2004–Sept 2005
CRUSADE.

100. 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
How important is IHD in women?
CVD is now recognized as an important cause of morbidity and mortality in women.
It afflicts 1 in 3 women and is the leading cause of death. In 2003, 483,842 women died from CVD compared with 267,902 who died from cancer.
Women develop CVD at an older age than men and tend to have a greater prevalence of multiple risk factors. Yet they are less likely to be referred for further testing following a positive exercise test and are less well treated.
The CVD mortality rate in women is greater than in men: 53% vs 47%.
This problem facing women is likely to become even greater as the population ages and the epidemics of obesity, metabolic syndrome, and diabetes continue.
Problem will increase as population ages and epidemics of obesity, metabolic syndrome, and diabetes continue
AHA. Pepine CJ. J Am Coll Cardiol. 2004;43:

101. AHA guidelines: Chest pain evaluation in women
Normal rest ECG, able to exercise
Diabetes, abnormal rest ECG, questionable exercise capacity
Intermediate risk
Exercise treadmill test
Stress cardiac imaging
Able to exercise or symptoms with low-level exercise
Low risk
Unable to exercise
Exercise stress
Pharmacologic stress
AHA guidelines: Chest pain evaluation in women
Normal or mildly abnormal test Normal LVEF
Moderately/severely abnormal test Reduced LVEF
Women have a lower prevalence of obstructive CAD and a higher prevalence of single-vessel CAD than men. Consequently, there is a higher false-positive rate on noninvasive testing.
A recent AHA consensus statement on evaluation of women with chest pain addresses this issue and places imaging tests earlier in the algorithm than for men.1
Risk factor modification ± anti-ischemic Rx
Cardiac catheterization
Mieres JH et al. Circulation. 2005;111:
Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the Guidelines for the Management of Patients with Chronic Stable Angina) Available at:

102. 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 (Raynaud’s, migraine, CAS)
Vasculitis (Takayasu’s, rheumatoid, SLE, CNSV, giant cell, etc)
IHD vasculopathy: Gender differences
Ischemic heart disease (IHD) in women is characterized by a number of structural and functional differences in the coronary vasculature compared with men.
These changes suggest that the consequences of an ischemic episode may be more severe in women than in men and that responses to medications may be less favorable.
CAS = coronary artery spasm
SLE = systemic lupus erythematosis
CNSV = central nervous system vasculitis
Pepine CJ et al. J Am Coll Cardiol. 2006;47:30S-5.

103. 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
Ischemia in women: Microvascular dysfunction
Obstructive CAD is less prevalent in women than in men. Many women have angiographically normal arteries yet experience angina.
Data from WISE study cohorts indicate that coronary artery microvascular dysfunction is a common cause of angina in women.
Microvascular dysfunction may also explain variability in outcome following PCI of a stenotic lesion in women.
A heightened awareness of this different form of IHD is necessary if all women at risk are to be identified and treated.
Reis SE et al. J Am Coll Cardiol. 1999;33:
Reis SE et al. Am Heart J. 2001;141:
Pepine CJ et al. J Am Coll Cardiol. 2006;47:30S-5.
Women’s Ischemia Syndrome Evaluation (WISE) study cohorts

104. Less obstructive CAD: Women vs men
Patients undergoing elective diagnostic angiography for angina
Less obstructive CAD: Women vs men
The American College of Cardiology-National Cardiovascular Data Registry™ (ACC-NCDR™) was established to standardize data collection for patients receiving cardiac catheterization and PCI.1
A new report from this registry shows that in patients undergoing elective diagnostic angiography for typical angina, women had a lower prevalence of obstructive CAD (lesion of >50% stenosis) than men.
Women
Men
ACC-National Cardiovascular Data Registry™. J Am Coll Cardiol
Brindis RG, Fitzgerald S, Anderson HV, Shaw RE, Weintraub WS, Williams JF. The American College of Cardiology-National Cardiovascular Data Registry™ (ACC-NCDR™): Building a national clinical data repository. J Am Coll Cardiol. 2001;37:

105. Women have more adverse outcomes vs men
Angina
~2x  morbidity/mortality MI
~1.5x  1-year mortality
CABG
~2x  morbidity/mortality
CAD
Women have more adverse outcomes vs men
Heart failure
~2x  incidence
Accumulated data show that in the setting of obstructive coronary disease, women have an overall worse prognosis than men.
Pepine CJ. J Am Coll Cardiol. 2004;43:

106. 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
Incidence (%)
Women
Men
Higher incidence of major CV events in women
The Euro Heart Survey enrolled patients with a clinical diagnosis of angina.
A higher proportion of women than men experienced death or MI during 1-year follow-up. This finding was observed in the whole population and in the subgroup with confirmed CAD.
Daly C et al. Circulation. 2006;113:490-8.

107. Increased risk of death/MI in women with CAD
Euro Heart Survey of Stable Angina; n = 718 men, n = 276 women with angiographic CAD
0.15
0.10
0.05
Log rank: P = 0.02
Cumulative event probability
Increased risk of death/MI in women with CAD
During a median follow-up of 13 months, women with angiographic CAD and stable angina were approximately twice as likely to suffer death or nonfatal MI than men (hazard ratio, 2.09; 95% CI 1.13–3.85; P = 0.02). 3 6 9 12 15 18
Time since entry (months)
Men
Women
Daly C et al. Circulation. 2006;113:490-8.

108. CRUSADE: Gender and discharge medications
N = 35,897 patients with UA/NSTEMI
100 80 60
Patients (%) 40 20
CRUSADE: Gender and discharge medications
Recent data from the CRUSADE registry document continuing undertreatment of women with CAD.
Aspirin
-blocker
ACEI
Statin
Clopidogrel
Discharge medications
Women
Men
Oct 2004–Sept 2005
P values not reported
CRUSADE.

109. Euro Heart Survey: Undertreatment of women
Euro Heart Survey of Stable Angina; n = 1582 women, n = 2197 men
100 * 80 * 60 * *
Patients (%) 40 20
Euro Heart Survey: Undertreatment of women
The CRUSADE discharge data discussed on the previous slide are supported by Euro Heart Survey of Stable Angina data documenting undertreatment of women in clinical practice.
Antiplatelet
ASA
Lipid-
Statin
-blocker
lowering
Women
Men
*P < 0.001
Daly C et al. Circulation. 2006;113:490-8.