• Shamir R Mehta, Christopher B Granger, William E Boden, Philippe Gabriel Steg, Jean-Pierre Bassand, David P Faxon, Rizwan Afzal, Susan Chrolavicius, Sanjit S Jolly, Petr Widimsky, Alvaro Avezum, Hans-Jurgen Rupprecht, Jun Zhu, Jacques Col, Madhu K Natarajan, Craig Horsman, Keith A A Fox, Salim Yusuf, and TIMACS Investigators.
• Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada. smehta@mcmaster.ca
• N. Engl. J. Med. 2009 May 21; 360 (21): 216521752165-75.

BackgroundEarlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain.MethodsWe randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography < or = 24 hours after randomization) or delayed intervention (coronary angiography > or = 36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. A prespecified secondary outcome was death, myocardial infarction, or refractory ischemia at 6 months.ResultsCoronary angiography was performed in 97.6% of patients in the early-intervention group (median time, 14 hours) and in 95.7% of patients in the delayed-intervention group (median time, 50 hours). At 6 months, the primary outcome occurred in 9.6% of patients in the early-intervention group, as compared with 11.3% in the delayed-intervention group (hazard ratio in the early-intervention group, 0.85; 95% confidence interval [CI], 0.68 to 1.06; P=0.15). There was a relative reduction of 28% in the secondary outcome of death, myocardial infarction, or refractory ischemia in the early-intervention group (9.5%), as compared with the delayed-intervention group (12.9%) (hazard ratio, 0.72; 95% CI, 0.58 to 0.89; P=0.003). Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (hazard ratio, 0.65; 95% CI, 0.48 to 0.89) but not in the two thirds at low-to-intermediate risk (hazard ratio, 1.12; 95% CI, 0.81 to 1.56; P=0.01 for heterogeneity).ConclusionsEarly intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients. (ClinicalTrials.gov number, NCT00552513.)2009 Massachusetts Medical Society

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