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