Initial Invasive or Conservative Strategy for Stable Coronary Disease (ISCHEMIA Trial)

ISCHEMIA is among the most consequential trials in cardiovascular medicine of the past generation. It randomized 5,179 patients with stable coronary disease and moderate or severe ischemia on stress testing to either an initial invasive strategy — angiography with revascularization when feasible, plus optimal medical therapy — or an initial conservative strategy — optimal medical therapy alone, with angiography reserved for treatment failure.

The invasive strategy did not reduce the composite primary endpoint over a median 3.2 years. Cardiovascular death or nonfatal MI occurred in 14.2 percent of the invasive group and 16.5 percent of the conservative group — a difference that was not statistically significant. All-cause mortality was identical. The invasive arm showed more early events (from periprocedural MI) while the conservative arm accumulated more late events, with the Kaplan-Meier curves crossing at approximately two years.

The trial dismantled a deeply held assumption in cardiology: that stress testing identifies ischemia, ischemia identifies revascularization targets, and revascularization improves prognosis. For the large population of patients with stable angina and objective ischemia on testing, this chain of inference turned out to be wrong — or at least not detectable over the follow-up periods achievable in randomized trials. Revascularization remains appropriate for refractory symptoms that optimal medical therapy cannot control, but it cannot be justified as prognosis-improving therapy in the stable patient.

We rate the evidence strong, with very high clinical significance. A landmark trial that fundamentally shifted the standard of care for stable coronary disease toward medical therapy first — one of the most practice-changing cardiovascular trials of the past decade.