Initial Invasive or Conservative Strategy for Stable Coronary Disease
Comprehensive Overview
Published in the New England Journal of Medicine in 2020, this study, known as the ISCHEMIA trial, asked whether patients with stable coronary artery disease and moderate or severe ischemia on stress testing do better with an invasive strategy, cardiac catheterization and revascularization added to medical therapy, than with medical therapy alone, a question left unresolved by earlier trials that enrolled patients with any level of ischemia rather than focusing on those thought most likely to benefit from intervention. Researchers randomly assigned 5,179 patients at 320 sites in 37 countries to an initial invasive strategy, angiography with revascularization when feasible, plus medical therapy, or to an initial conservative strategy of medical therapy alone, with angiography reserved for cases where medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, tracked over a median follow-up of 3.2 years, with a key secondary outcome of death from cardiovascular causes or myocardial infarction alone. The topline result was that the invasive strategy did not reduce the incidence of this composite outcome or death from any cause compared with the conservative strategy.
Outcomes and Implications
The most important finding was that over a median of 3.2 years, the primary composite outcome occurred in 318 patients assigned to the invasive strategy and 352 assigned to the conservative strategy, with no statistically significant difference between groups. The two strategies actually produced opposing patterns over time: at 6 months, event rates were higher with the invasive strategy, 5.3% versus 3.4%, largely reflecting procedure-related heart attacks, while by 5 years the trend had reversed, with cumulative event rates of 16.4% for the invasive strategy versus 18.2% for the conservative strategy, though this later difference was not statistically definitive either. Results for the key secondary outcome, death from cardiovascular causes or heart attack, followed a similar pattern. Deaths from any cause were nearly identical between groups, 145 with the invasive strategy versus 144 with the conservative strategy. Notably, the trial's findings were sensitive to how heart attacks were defined; using a broader definition that counted more procedure-related infarctions, the early risk associated with the invasive strategy grew larger. No evidence emerged that any subgroup, based on diabetes status, angina frequency, or ischemia severity, benefited more from one strategy than the other. The authors conclude that among patients with stable coronary disease and moderate or severe ischemia, an initial invasive strategy did not reduce the risk of ischemic cardiovascular events or death from any cause compared with an initial conservative strategy, underscoring that routine early intervention offers no clear advantage in this population.