International Study of Comparative Health Effectiveness With Medical and Invasive Approaches - ISCHEMIA
ACC

CONTRIBUTION TO LITERATURE - The ISCHEMIA trial failed to show that routine invasive therapy was associated with a reduction in major adverse ischemic events compared with optimal medical therapy among stable patients with moderate ischemia.

DESCRIPTION - The goal of the trial was to evaluate routine invasive therapy compared with optimal medical therapy among patients with stable ischemic heart disease and moderate to severe myocardial ischemia on noninvasive stress testing.

STUDY DESIGN - Randomized, Parallel

Patients with stable ischemic heart disease and moderate to severe ischemia were randomized to routine invasive therapy (n = 2,588) versus medical therapy (n = 2,591).

In the routine invasive therapy group, subjects underwent coronary angiography and percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) as appropriate.

In the medical therapy groups, subjects underwent coronary angiography only for failure of medical therapy.

    - Total number of enrollees: 5,179

    - Duration of follow-up: 3.3 years

    - Mean patient age: 64 years

    - Percentage female: 23%

    - Percentage with diabetes: 41%

INCLUSION CRITERIA

    - Patients >20 years of age

    - Moderate to severe ischemia on noninvasive stress testing (nuclear ≥10% ischemia; echo ≥3 segments of ischemia; cardiac magnetic resonance ≥12% ischemia and/or ≥3 segments with ischemia; exercise treadmill test ≥1.5 mm ST depression in ≥2 leads or ≥2 mm ST depression in single lead at <7 METs with angina)

EXCLUSION CRITERIA

    - ≥50% left main stenosis (from blinded computed tomography)

    - Advanced chronic kidney disease (estimated glomerular filtration rate <30 ml/min)

    - Recent myocardial infarction

    - Left ventricular ejection fraction <35%

    - Left main stenosis >50%

    - Unacceptable angina at baseline

    - New York Heart Association class III-IV heart failure

    - Prior PCI or CABG within last year

Angina frequency at baseline

    None, 34%

    Several times per month, 44%

    Daily/weekly, 22%

Other salient features/characteristics:

    Over the entire follow-up period, cardiac catheterization was performed in 96% of the invasive group vs. 28% of the medical therapy group

    Over the entire follow-up period, coronary revascularization was performed in 80% of the invasive group vs. 23% of the medical therapy group

PRINCIPAL FINDINGS

The primary outcome of cardiovascular death, myocardial infarction, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure at 3.3 years occurred in 13.3% of the routine invasive group compared with 15.5% of the medical therapy group (p = 0.34). The findings were the same in multiple subgroups.

Invasive therapy was associated with harm (~2% absolute increase) within the first 6 months and benefit within 4 years (~2% absolute decrease).

SECONDARY OUTCOMES

    Cardiovascular death or myocardial infarction: 11.7% of the routine invasive group compared with 13.9% of the medical therapy group (p = 0.21)

    All-cause death: 6.4% of the routine invasive group compared with 6.5% of the medical therapy group (p = 0.67)

    Periprocedural myocardial infarction: (invasive/conservative hazard ratio [HR] 2.98, 95% confidence interval [CI] 1.87-4.74)

    Spontaneous myocardial infarction: (invasive/conservative HR 0.67, 95% CI 0.53-0.83)

QUALITY OF LIFE OUTCOMES - Improvement in symptoms was observed among those with daily/weekly/monthly angina, but not in those without angina.

INTERPRETATION - Among patients with stable ischemic heart disease and moderate to severe ischemia on noninvasive stress testing, routine invasive therapy failed to reduce major adverse cardiac events compared with optimal medical therapy. There was also no benefit from invasive therapy regarding all-cause mortality or cardiovascular mortality/myocardial infarction. One-third of subjects reported no angina symptoms at baseline. Routine invasive therapy was associated with harm at 6 months (increase in periprocedural myocardial infarctions) and associated with benefit at 4 years (reduction in spontaneous myocardial infarction). These results do not apply to patients with current/recent acute coronary syndrome, highly symptomatic patients, left main stenosis, or left ventricular ejection fraction <35%.

Although the overall interpretation of this trial was negative, there were mixed findings with evidence for both harm and benefit. This signals that: 1) invasive therapy for stable ischemic heart disease patients needs to be carefully considered in the context of angina burden and background medical therapy, and 2) likelihood that optimal coronary revascularization can be achieved with low procedural complications.

REFERENCES

1. Presented by Judith S. Hochman at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019.

2. Presented by John A. Spertus at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019 (quality of life outcomes).