It is important to note that although both the biomarker and TIMI risk stratification findings (i.e., patients with negative troponins or patients with TIMI risk score 0-2 do not benefit from an early invasive strategy) are often incorporated into routine clinical practice, the interaction between the primary outcome and these individual subgroups did not reach statistical significance however, given stark numerical differences and apparent risk-response pattern within the TIMI score group (i.e., as TIMI risk increased, benefit with early angiography increased), lack of statistical interaction likely reflects underpowered subgroups in this case rather than a spurious finding. Overall the results of TACTICS-TIMI 18 provide practical guidance for the selection of patients who are most likely to benefit from early coronary angiography and intervention in non-STEMI ACS. Importantly, patients with TIMI score 0-2 and patients with undetectable troponins (25% of the study population) did not appear to benefit from routine angiography and PCI, suggesting that it is reasonable to pursue stress testing in these low-risk patients with intervention reserved for patients with significant ischemia on functional testing. Notably there was no mortality benefit with an early invasive approach, and this strategy was associated with a 2% absolute increase in protocol-defined bleeding. This benefit was most apparent in patients presenting with ST segment changes, troponin elevation at presentation, and patients with intermediate or high TIMI risk scores (3 or greater). TACTICS-TIMI 18 demonstrated a clear reduction in major adverse cardiovascular events with an early invasive approach, driven primarily by a reduction in nonfatal MI and recurrent ischemia. Overall, 60% of patients in the early invasive arm underwent revascularization versus 36% in the conservative arm. In the conservative strategy, patients underwent coronary angiography only if noninvasive stress testing was positive or there was failure of medical therapy (prolonged angina at rest, hemodynamic instability, recurrent angina or MI). In the early invasive strategy arm, 97% of patients underwent coronary angiography a median of 22 hours (all within 48 hours) after presentation with PCI or CABG to culprit lesions. The 2001 Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy - Thrombolysis in Myocardial Infarction 18 (TACTICS-TIMI 18) trial randomized 2220 patients to either a protocolized early invasive strategy versus a delayed selectively invasive strategy with each arm receiving the IIb/IIIa inhibitor tirofiban. Unlike patients presenting with STEMI in which there is a clear mortality benefit to emergent coronary angiography and PCI, it is less clear whether patients with non-STEMI ACS (unstable angina or non-ST segment elevation MI) also benefit from routine early angiography and intervention. This benefit was largely limited to higher risk patients with TIMI score > 2. In patients with unstable angina or non-ST segment elevation MI, an early invasive strategy (in combination with glycoprotein IIb/IIIa inhibition with tirofiban) significantly reduced major cardiovascular events versus a selectively invasive strategy. In patients with unstable angina or non-ST segment elevation MI, does an early invasive PCI strategy reduce major cardiovascular events versus a more conservative, selectively invasive PCI strategy?
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