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Evevident
Original paper
2020NEJMCardiology

ISCHEMIA

Initial Invasive or Conservative Strategy for Stable Coronary Disease

RCTStable CAD

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Overview

In stable CAD with moderate/severe ischemia, an initial invasive strategy did not reduce major ischemic events or death versus conservative therapy over the primary follow-up.

Clinical takeaway

ISCHEMIA modernized COURAGE: even in moderate-to-severe ischemia, routine early angiography/revascularization does not clearly improve hard outcomes, though it can improve angina in symptomatic patients.

Key result

No significant reduction in the primary outcome with an initial invasive strategy (adjusted HR 0.93; 95% CI 0.80-1.08).

Practice impact

Supports conservative initial management for many stable CAD patients after excluding left main disease, with revascularization for symptoms or high-risk features.

Evidence

Study design

Randomized, open-label, controlled strategy trial.

Enrollment

5,179

Follow-up

Median 3.2 years.

Geography

Multinational, 320 sites in 37 countries

Clinical question

Does an initial invasive strategy improve outcomes compared with an initial conservative strategy in stable CAD with moderate or severe ischemia?

Population

  • Patients with stable coronary disease and moderate or severe ischemia on stress testing; left main disease was excluded by coronary CT angiography when feasible.

Intervention

Early angiography and revascularization when feasible plus optimal medical therapy.

Comparator

Initial optimal medical therapy with angiography reserved for failure of medical therapy or events.

Primary outcome

Composite of CV death, MI, hospitalization for unstable angina, hospitalization for HF, or resuscitated cardiac arrest.

An initial invasive strategy did not significantly reduce the primary composite outcome compared with an initial conservative strategy.

Hazard ratio / 0.93 / CI 95% CI 0.80-1.08 / p=0.34

Key results

  • Primary composite outcome: 318 events with the invasive strategy vs 352 with the conservative strategy; adjusted HR 0.93; 95% CI 0.80-1.08; p=0.34.
  • Event curves crossed: at 6 months the invasive strategy had a higher cumulative event rate (5.3% vs 3.4%), but at 5 years a lower rate (16.4% vs 18.2%).
  • All-cause mortality did not differ (145 vs 144 deaths; HR 1.05; 95% CI 0.83-1.32).
  • Angina-related quality of life improved most with the invasive strategy in patients with frequent baseline angina.

Harms

  • The invasive strategy carried early periprocedural risk, with a higher cumulative event rate in the first 6 months (5.3% vs 3.4%).
  • Findings were sensitive to the definition of myocardial infarction, with more procedural MIs of uncertain clinical importance when a broader definition was used.

Clinical Use

When to cite

  • When explaining why stable patients with moderate-to-severe ischemia do not automatically need an early invasive strategy if left main disease is excluded.

Practice impact

  • Supports conservative initial management for many stable CAD patients after excluding left main disease, with revascularization for symptoms or high-risk features.

Applicability

  • Most applicable to patients with stable coronary disease and moderate or severe ischemia in whom left main disease has been excluded.
  • Does not apply to acute coronary syndromes, significant left main stenosis, low ejection fraction, or highly symptomatic angina, which were excluded or under-represented.

Limitations

  • Excluded left main disease.
  • Not a trial of unstable ACS.
  • Interpretation complicated by procedural MI versus spontaneous MI definitions.
  • Open-label strategy design and slower-than-planned enrollment reduced statistical power.

Common misinterpretations

  • Do not read ISCHEMIA as showing revascularization has no role; it improved angina and quality of life in symptomatic patients.
  • Do not apply ISCHEMIA to acute coronary syndromes or to left main disease, which were excluded.

Related evidence

COURAGE - Earlier TrialFAME 2 - Contrasting Result

Citation

Maron DJ, Hochman JS, Reynolds HR, et al. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020;382(15):1395-1407. doi:10.1056/NEJMoa1915922

Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years.