Does early invasive intervention improve outcomes in patients with non-ST-segment-elevation myocardial infarction?

Angiography within 24 hours of presentation of non-ST-segment-elevation myocardial infarction (NSTEMI) decreases recurrent ischemia but does not decrease mortality. This study, however, was not large enough to detect a clinically relevant reduction in mortality of at least 15% if it truly exists. In the subset of patients at highest risk of death or myocardial infarction (MI), early angiography decreases the combined outcome of death, MI, or stroke. Individual outcome data for this high-risk population was not reported. Although there may not be an urgent need for early intervention in most NSTEMI patients, those at higher risk should make an earlier trip to the catheterization laboratory. (LOE = 1b)

Mehta SR, Granger CB, Boden WE, et al, for the TIMACS Investigators. Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med 2009;360(21):2165-2175.  [PMID:19458363]

Randomized controlled trial (single-blinded)

Industry + govt

Concealed

Inpatient (any location)

Using concealed allocation, these investigators conducted a large, multicenter trial, randomizing 3031 patients with NSTEMI to receive coronary angiography either within 24 hours or after 36 hours of presentation. Patients met 2 of the following 3 criteria: age of 60 or older, elevated cardiac markers, or EKG findings compatible with ischemia. The analysis was by intention to treat with good (99%) follow-up in both groups. There were more crossovers, due to prespecified criteria, of patients from the delayed intervention group to early intervention than the other way around (20.5% vs 9.9%), but it is unclear whether this had an impact on the results. The median time to intervention in the early group was 14 hours, compared with 50 hours in the delayed group. Early angiography did not significantly reduce the primary outcome of the combination of death, MI, or stroke at 6 months. However, the study only had the ability to find a 28% risk reduction or greater. Although a smaller difference in risk reduction may be clinically relevant, this study did not have the power to detect it, if it exists. For every 44 patients treated with early intervention, there was one less episode of recurrent ischemia (number needed to treat [NNT] = 44; 95% CI, 37-67). In addition, for every 16 patients at the highest risk of death or MI (as indicated by a risk score based on age, hemodynamic status, kidney function, presence of heart failure, ST-segment changes, and elevated cardiac markers) who received early intervention, there was one less episode of the combined outcome of death, MI, or stroke (NNT=16; 10-54). Bleeding rates were similar in both groups (3.1% vs 3.5%).