Yogita RochlaniPGY2

EVALUATION AND MANAGEMENT OF STABLE ISCHEMIC HEART DISEASE

Spectrum of IHD

Acute Coronary Syndrome • ST elevation MI• Non ST elevation MI• Unstable angina • SCD

Stable IHD• Chronic stable

angina• New onset angina in

patients with suspected IHD

Differences in plaque morphology

Vulnerable Plaque (ACS)

Thin fibrous caps

Large lipid core

Less SM cells and macrophages and less collagen

Expansive remodeling of wall

Cause supply ischemia

Stable Plaque (CSA)

Thick fibrous caps

Small lipid core

more SM cells and macrophages, and more collagen

Constrictive remodeling of wall

Cause demand ischemia

Case Scenario• 72 year old female reports experiencing chest pain 3 weeks ago while she was out walking. Her chest and left shoulder felt tight. She stopped walking and rested and the pain eased. She did not seek medical help at the time because she thought it was a side stitch. Soon she began to experience some chest heaviness during her daily walks and she had to stop a few times for it to ease up before she could continue walking again. Today she comes to clinic for her primary care appointment.

• What would you do?

Approach

History

• Age, Gender• Pain

characteristics• Associated

symptoms• History of

cardiovascular disease

• Cardiovascular risk factors

Physical Exam

• e/o atherosclerotic disease in other organs (PVD, AAA, carotid disease)

• r/o non coronary causes

• Other cardiopulmonary findings

Lab exam

• CBC• Renal chem 10• UA for DM and

microalbuminuria

• Lipid panel• HbA1c• Thyroid

function (if indicated)

• CRP• CXR may show

cardiomegaly, pul edema

ECG

• LVH• Rhythm

disturbances• Signs of old MI• Conduction

delays• Normal

Clinical Classification of Chest Pain

Anginal Equivalents : Dyspnea, Nausea, Fatigue, usually in elderly and diabetic patients

Angina

Stable

Unstable

Low risk

Moderate risk

High riskVasospastic

Features of unstable angina

Rest angina Angina occurring at rest and usually prolonged >20 min, occurring within 1 week of presentation

New-onset angina Angina of at least CCS Class III severity with onset within 2 months of initial presentation

Increasing angina Previously diagnosed angina that is distinctly more frequent, longer in duration, or lower in threshold (i.e., increased by ≥1 CCS class within 2 mo of initial presentation to at least CCS Class III severity)

Canadian Cardiovascular Society classification of severity of angina

What would you do next?

1) Admit for ACS rule out

2) Schedule for cardiac catheterization

3) Outpatient TMST

4) Outpatient Dobutamine stress echo

5) Discharge with medical management

APPROACH TO DIAGNOSIS AND RISK ASSESSMENT IN PATIENTS WITH NEW ONSET ANGINA OR STABLE ANGINA

2012 ACC/AHA/ACP Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease

1) Initial diagnostic approach to a patient with suspected IHD or new onset anginal symptoms ( once ACS has been ruled out)

2) Risk assessment approach to determine the risk of death, AMI in patients with stable ischemic heart disease.

3) Outline management strategies

Pretest Likelihood of CAD in Symptomatic Patients According to Age and Sex* (Combined Diamond/Forrester and CASS Data)

*Each value represents the percent with significant CAD on catheterization.

*Each value represents the percent with significant CAD on catheterization.

Pre- test Probability of IHDEstimated based on age, gender, and character of chest pain

Low Probability (<10%) Asymptomatic men and women of all ages Women < 50 years with atypical chest pain

Intermediate Probability (10%-90%)

Men of all ages with atypical angina Women ≥ 50 years with atypical anginaWomen 30-50 years with typical angina

High Probability (90%) Men ≥ 40 years with typical angina Women ≥60 years with typical angina

Ref: MKSAP

Coronary Calcium Scoring

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease

Non Invasive Testing for diagnosis of stable IHD

Exercise testing• ECG • Echocardiography• MPI

Pharmacologic testing• Stressor – dobutamine stress echocardiogrpahy• Vasodilator - adenosine, dipyridamole or regadenoson used for

nuclear perfusion imaging

Anatomic testing• CCTA• CMRA• CAC scoring

Exercise Electrocardiography

• Diagnostic endpoint is 1 mm horizontal or down-sloping ST-segment depression at peak exercise or ST-segment elevation consistent with an ACS.

• Sensitivity 61% and specificity ranges from 70% to 77%.

Advantages:• Improved diagnostic accuracy with additional non-ECG factors, such

as exercise duration, chronotropic incompetence, angina, ventricular arrhythmias, heart rate recovery, and hemodynamic response to exercise (i.e., drop in systolic BP).

Limitations and Risks:• Resting ECG abnormalities • Maximal exercise testing is associated with a low but finite incidence

of cardiac arrest, AMI, and even death.

Pharmacologic stress echocardiography

• Diagnostic endpoint is new or worsening wall motion abnormalities and changes in global LV function during or immediately after stress.

• Advantages- Information about LV function and valvular abnormalities, if any.

• Limitations & Risks:

- Reduced image quality in obese individuals and those with chronic lung diseases.

- Drug-specific adverse events (dobutamine: ventricular arrhythmias)

Exercise Pharmacologic

Sensitivity 70-85% 85-90%

Specificity 77-89% 79-90%

Nuclear Myocardial Perfusion SPECTVasodilator agents administered as a continuous infusion (adenosine,dipyridamole) or bolus (regadenoson) injection to expose hetrogenity in perfusion.

• Diagnostic endpoint of nuclear MPI is reduction in myocardial perfusion.

• Limitations and Risks:- Diagnostic image quality is affected in obese patients, women with

large breasts.- Global reductions in myocardial perfusion, such as in the setting of left

main or 3-vessel CAD, can result in balanced reduction and an underestimation of ischemic burden.

- Radiation exposure.

Exercise Pharmacologic

Sensitivity 82-88% 88-91%

Specificity 70-88% 75-90%

Risk Stratification

*Although the published data are limited; patients with these findings will probably not be at low risk in the presence of either a high-risk treadmill score or severe resting LV dysfunction (LVEF <35%).

Treatment Strategies1. Patient education 2. Risk factor modification pharmacological

and non-pharmacological methods.3. Anti-anginal therapy with nitrates, beta

blockers, CCBs. 4. Use revascularization by percutaneous

catheter-based techniques or CABG when there is clear evidence of the potential to improve patients’ symptoms and/or survival.

*** Cornerstone of management is MEDICAL THERAPY and benefits of PCI as an initial management approach are questionable.

Algorithm for Guideline-Directed Medical Therapy for Patients With SIHD

NEJM April 2007

CLINICAL OUTCOMES UTILIZINGREVASCULARIZATION AND AGGRESSIVEDRUG EVALUATION (COURAGE) TRIAL

Background• Until 2004, 85% PCI procedures we done electively on patients with stable coronary artery disease.

• PCI is known to have mortality benefit in acute coronary syndromes.

• Mortality benefit in stable ischemic heart disease is unclear, although there is evidence for symptomatic benefit (relief from pain and increase in exercise tolerance).

Question•PCI coupled with optimal medical therapy reduces the risk of death and non fatal myocardial infarction in patients with stable coronary artery disease when compared with optimal medical therapy alone.

Study Description• Multicenter, open-label, parallel-group, randomized, controlled trial

• Permuted block randomization • N=2,287

• PCI plus OMT (n=1,149) • OMT alone (n=1,138)

• Setting: 50 centers in US and Canada • Enrollment: June 1999 to January 2004 • Median follow-up: 4.6 years • Analysis: Intention-to-treat

Study PopulationInclusion Criteria• Stable CAD with Canadian Cardiovascular Society (CCS) class I, II, III or stabilized class IV angina AND

• ≥70% stenosis in at least one coronary artery and objective myocardial ischemia, with any of: 1. Substantial changes in ST segment depression or T wave

inversion on the resting EKG

2. Inducible ischemia with either exercise or pharmacologic stress test

OR • 80% stenosis with classic angina without provocative testing

Exclusion Criteria• Persistent CCS class IV angina • Markedly positive treadmill test (significant ST segment depressions and/or hypotensive response during stage I of Bruce protocol)

• LVEF <30% • Refractory CHF • Cardiogenic shock • ≥50% left main disease • Revascularization within the previous 6 months • Coronary lesions deemed unsuitable for PCI

Study design

Intervention

Group 1N=1149

PCI + OMT

Group 2N=1138

OMT

Optimal Medical Therapy (OMT)

1. Antiplatelet agents – Aspirin 81 to 325 mg per day or 75 mg of Clopidogrel per day, if aspirin intolerance for all patients. Combination in patients with PCI.

2. Beta blockers – Long acting Metoprolol

3. Calcium channel blockers - Amlodipine

4. Nitrates - ISMN

5. ACE/ ARBs – Lisinopril/ Losartan

6. Lipid level reduction – Simvastatin alone or with Ezetimibe for target level of LDL level of60 to 85 mg per deciliter.

7. Guideline based recommendations for smoking cessation, diet and exercise.

• After the LDL cholesterol target was achieved, HDL cholesterol increase to a level above 40 mg per and triglyceride level decrease to less than 150 mg per deciliter (1.69 mmol per liter) with exercise, extended-release niacin, or fibrates, alone or in combination were attempted.

Percutaneous Intervention and OMT

Target-lesion revascularization always attempted and complete revascularization was performed as clinically appropriate.

• Angiographic success ;

Normal coronary-artery flow with

1. < 50% stenosis after balloon angioplasty, or

2. < 20% after coronary stent implantation

• Clinical success was defined as angiographic success plus absence of in hospital myocardial infarction, emergency CABG, or death.

• Drug-eluting stents were not approved for clinical use until the final 6 months of the study, so only used in 31 patients.

Outcomes

Primary

Composite of death from any

cause and nonfatal

myocardial infarction.

Secondary

Composite of death, MI, stroke

and hospitalization for unstable angina with negative biomarkers.

Statistical Analysis• Crude survival analysis using Kaplan-Mier method for primary and secondary outcomes.

• Adjusted analysis for co-variates using Cox proportional harzards regression model.

• Analyses were performed according to the intention to treat principle.

• T test for continuous variables.• Chi square test for categorical variables.

Results – Baseline Characteristics

Primary Outcome: Composite of death and non fatal MI • 211 patients in the PCI group and 202 patients

in the medical-therapy group.

• Estimated 4.6-year cumulative primary event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (unadjusted hazard ratio for the PCI group, 1.05; 95% CI, 0.87 to 1.27;P = 0.62)

• In subgroup analysis, even among patients with multivessel coronary artery disease, previous myocardial infarction, and diabetes, the rate of the primary end point was similar for both groups.

Secondary Outcomes

• For the pre specified composite outcome of death, nonfatal myocardial infarction, and stroke, the event rate was 20.0% in the PCI group and 19.5% in the OMT group.

PCI +OMT OMT Hazard Ratio

Death 7.6% 8.3% 0.87; 95% CI, 0.65 to 1.16

Rate of MI 13.2% 12.3% 1.13; 95% CI, 0.89 to 1.43; P = 0.33

Stroke 2.1% 1.5% 1.56; 95% CI, 0.80 to 3.04; P = 0.19

Rates of hospitalization for ACS

12.4% 11.8% 1.07;95% CI, 0.89 to 1.43; P=0.33

Additional outcomes• Reduction in prevalence of angina was noted in both groups.

-- Initial statistically significant difference noted in favor of the PCI group.

-- At 5 years, 74% of patients in the PCI group and 72% in the medical therapy group were free of angina (P = 0.35).

• Additional revascularization performed for angina that was unresponsive to maximal medical therapy or when there was objective evidence of worsening ischemia on noninvasive testing.

-- 21.1% of patients in the PCI group

-- 32.6% of those in the medical-therapy group

(hazard ratio, 0.60; 95% CI, 0.51 to 0.71; P<0.001).

Survival Analysis

Subgroup Analysis

What does this mean?• Addition of PCI to optimal medical therapy did not reduce long term rates of death, nonfatal myocardial infarction, strokes, and hospitalizations for ACS.

• Greater symptom relief from angina noted with PCI in the initial period but it by the end of the follow up period, medical therapy group also achieved similar results.

• Hence, as an initial management approach, optimal medical therapy without routine PCI can be implemented safely in the majority of patients with stable coronary artery disease, even in those with extensive, multi-vessel involvement and inducible ischemia.

Limitations• Preponderance of male patients (85%)and lack of ethnic diversity ( only 14% non white patients).

• Bare metal stents used for most PCIs as DES were only approved for use towards the end of the study.

• Likely incomplete revascularization given discordance between the incidence of multivessel disease and procedures with multiple stents placed

• Unclear how long patients took clopidogrel or if extended duration of therapy would improve outcomes in the PCI group

Strengths• Randomized• Large population• Compliance• Adequate follow up• VA population

Impact

Howard D, Shen Y. Trends in PCI Volume after Negative Results from the COURAGE Trial. Health Services Research; 49(1pt1): 153-170.

17- 25% reduction in PCI for stable heart disease.

(United States: 1979-2006). Source: NCHS and NHLBI.

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CVD disease mortality trends for males and females

Other Studies• Bypass Angioplasty Revascularization Investigation 2

Diabetes (BARI 2D 2009) - 2,368 patients with T2DM and stable CAD randomized to CABG, OMT or OMT and PCI. PCI and only OMT groups did not show any difference.

Frye RL, et al. "A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease". The New England Journal of Medicine. 2009. 360(24):2503-2515.

• FAME (FFR guided PCI vs. angiography guided PCI) and FAME 2 ( FFR guided PCI vs. OMT) -patients with multivessel CAD, an FFR-guided approach reduces the composite of death, nonfatal MI, and need for repeat/urgent revascularization.

De Bruyne B, et al. "Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease". The New England Journal of Medicine. 2012. 367(11):991-1001.

• ISCHEMIA trial (2012-1019, 8000 patients) - Initial invasive strategy of cardiac catheterization followed by optimal revascularization with OMT compared with only OMT. Ongoing.