Background: In aggregate, published randomized trials of invasive versus conservative treatment in patients with unstable angina and non-ST-segment elevation myocardial infarction support an invasive strategy, but the optimal timing of an invasive approach is not fully established. The Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS) Thrombolysis in Myocardial Infarction (TIMI)-18 Trial treated all patients with upstream intravenous tirofiban and heparin for 48 hours or until revascularization, and randomized subjects to an invasive or conservative approach. We hypothesized that patients who underwent earlier intervention in the invasive arm would have improved outcomes.
Methods: We evaluated 1,078 participants from the invasive arm, who underwent angiography stratified by time after randomization to the procedure. The composite outcome was death, myocardial infarction (MI), or rehospitalization.
Results: At 6 months, the rates of the composite outcome were 15.4 and 19.5% for those undergoing catheterization before and after 48 hours after randomization, respectively, P = 0.34. Rates of individual endpoints were similar except MI, which occurred in 2.9 versus 6.5%, in those who underwent angiography before or after 48 hours, respectively, P = 0.08.
Conclusion: We could not identify a benefit to early intervention on hard endpoints. There were level time-dependent risks of cardiac events during a period of 48 hours prior to cardiac catheterization possibly due to the effect of glycoprotein IIb/IIIa receptor inhibition. Considering that the groups were not randomized based on time and the potential selection bias in this analysis, these data should be considered only hypothesis generating. A prospective, randomized trial is warranted to explore whether immediate invasive strategy is better than an early invasive strategy in the setting of glycoprotein IIb/IIIa receptor inhibition.