Little if any benefit to early invasive strategy for stable angina and at least moderate reversible ischemia (ISCHEMIA trial)

Référence

Maron DJ, Hochman JS, Reynolds HR, et al, for the ISCHEMIA Research Group. Initial invasive or conservative strategy for stable coronary disease. N Engl J Med 2020;382(15):1395-1407.

Sommaire

These investigators identified patients with stable angina and moderate to severe reversible ischemia on a stress test that included imaging, or severe reversible ischemia on a stress test without imaging. Most patients underwent coronary computed tomography angiography to rule out left main disease or the absence of obstructive coronary disease. The authors excluded patients with impaired ejection fraction, impaired renal function, recent acute coronary syndrome, or left main stenosis greater than 50%. The median age of participants was 64 years, 77% were men, 42% had diabetes, and 19% had a previous myocardial infarction (MI). Groups were balanced at the beginning of the study and analysis was by intention to treat. The original goal was to randomize 8000 patients and follow them up for 4 years, but slow recruitment led to a smaller sample size and a change in the primary outcome to a composite of death from cardiovascular causes, MI, hospitalization for unstable angina, heart failure, or cardiac arrest. Ultimately, 5179 patients were randomized to receive an initial invasive strategy (medical therapy and angiography, followed by revascularization, if indicated) or a strategy of medical therapy alone with angiography reserved for patients who failed medical therapy. Patients were followed up for a median of 3.2 years. In both groups, both the primary composite and a secondary composite of acute MI or cardiovascular death were more common during the first year after enrollment due to periprocedural MIs. This increase was even greater when using a less restrictive definition of procedural MI. During subsequent years, there was a nonsignificant trend favoring the invasive strategy. There was no significant difference between groups for the primary outcome (12.3% invasive vs 13.6% medical; hazard ratio 0.93; 95% CI 0.80 - 1.08), no significant difference in the secondary composite of cardiovascular death or MI, and no difference in all-cause mortality (145 vs 144 deaths). Although 79% in the invasive strategy group underwent revascularization, only 21% required it in the medical therapy group. There were 5337 procedures in the invasive group and only 1506 in the medical therapy group, which is a large difference in resource consumption and cost. Subgroup analyses revealed trends toward greater benefit in patients with more vessels involved, in those with proximal left anterior descending coronary artery involvement, and in patients with more ischemia at baseline. An analysis of angina symptom scores found improvement with invasive therapy in those with weekly or monthly angina at baseline, but not in those with no reported angina. However, these differences of a few points were unlikely to be clinically meaningful (see Spertus, et al. N Engl J Med 2020;382:1408-1419).