Asymptomatic Cardiac Ischemia Pilot Study - ACIP


Revascularization vs. medical strategies for 2-year mortality in asymptomatic ischemia.


Significant differences exist in the ability of three treatment strategies (angina-guided, ischemia-guided, and revascularization) to suppress asymptomatic ischemia.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 618
Mean Follow Up: 1 year
Female: 14
Mean Ejection Fraction: <35%: 2% of patients; 35% to 49%: 10% of patients; 50% to 64%: 44% of patients; > 65%: 45% of patients

Patient Populations:

Arteriographically documented coronary artery disease (> 50% diameter stenosis) amenable to revascularization
At least one episode of asymptomatic ischemia on a 48-h ambulatory ECG
Evidence of ischemia on a treadmill exercise test

Primary Endpoints:

Absence of cardiac ischemia on the 48-h ambulatory ECG at the 12-week visit and at 1-year and 2-year follow-up.

Secondary Endpoints:

Exercise test outcome measurements
Additional measurements from the ambulatory ECG
Clinical outcomes.

Drug/Procedures Used:

Blinded, assigned randomly to medical therapy groups, unless one regimen was contraindicated

Atenolol plus nifedipine regimen:
Step 1: atenolol, 50 mg qd
Step 2: atenolol, 100 mg qd
Step 3: atenolol, 100 mg qd plus nifedipine XL, 30 mg qd<.

Concomitant Medications:

Diltiazem (60 mg bid, allowed for post infarction patients) Atenolol (50 mg qd, allowed for post infarction patients)

Principal Findings:

After 1 year:
The mortality rate was 4.4% in the angina-guided group; 1.6% in the ischemia-guided group, and 0% in the revascularization group (overall, p = 0.004; angina-guided vs revascularization, p = 0.003; other pairwise comparisons, p = NS).

The revascularization group received less medication and had less ischemia on serial ambulatory ECG recordings and exercise testing than those assigned to medical strategies.

The ischemia-guided group received more medication, but had suppression of ischemia similar to the angina-guided group.

Frequency of MI, unstable angina, stroke and congestive heart failure were not significantly different among the groups.

The revascularization group had significantly fewer hospital admissions and nonprotocol revascularization.

Incidence of death, myocardial infarction, nonprotocol revascularization or hospital admission was 32% with the angina-guided strategy; 31% with the ischemia-guided strategy; and 18% with the revascularization strategy (p=0.003).

After 2 years:
Total mortality was 6.6% in the angina-guided strategy group, 4.4% in the ischemia guided strategy group, and 1.1% in the revascularization strategy group (p < 0.02).

The rate of death or MI was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (p < 0.04).

The rate of death, MI, or recurrent cardiac hospitalization was 41.8% in the angina guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (p < 0.001).

Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison.

Women tended to have more risk factors for CAD and less severity in anatomical disease, which may explain why women are less likely than men to have coronary bypass surgery.

Myocardial ischemia detected by ambulatory ECG and an abnormal ETT are each independently associated with an adverse cardiac outcome in patients subsequently treated medically.


After 1 year and 2 years, revascularization was superior to both angina-guided and ischemia-guided medical strategies in suppressing asymptomatic ischemia and was associated with better outcomes. These findings require confirmation by a larger long term trial. More study is also required to test the potential of more aggressive drug therapy.


1. J Am Coll Cardiol 1994;24:1-10. Design and baseline results
2. J Am Coll Cardiol 1994;24:11-20. Final results
3. J Am Coll Cardiol 1995:26:594-605. One-year follow-up
4. Am J Cardiol 1996;77:1302-9. Medical therapy subgroup
5. Am J Cardiol 1997;80:1395-401. Ambulatory EKG and ETTs
6. Circulation 1997;95:2037-43. Two-year follow-up
7. Clinical Cardiology 1998;21:184-90. Gender subgroups

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and Coronary Artery Disease

Keywords: Coronary Artery Disease, Myocardial Ischemia, Stroke, Myocardial Infarction, Risk Factors, Constriction, Pathologic, Electrocardiography, Nifedipine, Heart Failure, Coronary Artery Bypass, Hospitalization, Exercise Test

< Back to Listings