Randomized comparison of upstream tirofiban versus downstream high bolus dose tirofiban or abciximab on tissue-level perfusion and troponin release in high-risk acute coronary syndromes treated with percutaneous coronary interventions: the EVEREST trial.

OBJECTIVES: We aimed to compare the effects of upstream tirofiban versus downstream high-dose bolus (HDB) tirofiban and abciximab on tissue level perfusion and troponin I release in high-risk non-ST-segment elevation acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI).

BACKGROUND: Optimal timing and dosage of glycoprotein IIb/IIIa inhibitors for ACS remain to be explored.

METHODS: We randomized 93 high-risk ACS patients undergoing PCI to receive upstream (in the coronary care unit) tirofiban, downstream (just prior to PCI) HDB tirofiban, and downstream abciximab. We evaluated the effects of the three drug regimens on tissue-level perfusion using the corrected Thrombolysis In Myocardial Infarction (TIMI) frame count, the TIMI myocardial perfusion grade (TMPG), and intracoronary myocardial contrast echocardiography (MCE) before and immediately after PCI and after cardiac troponin I (cTnI).

RESULTS: The TMPG 0/1 perfusion was significantly less frequent with upstream tirofiban compared with HDB tirofiban and abciximab both before (28.1% vs. 66.7% vs. 71%, respectively; p = 0.0009) and after PCI (6.2% vs. 20% vs. 35.5%, respectively; p = 0.015). Upstream tirofiban was also associated with a significantly higher MCE score index (0.88 +/- 0.18 vs. 0.77 +/- 0.32 vs. 0.71 +/- 0.30, respectively; p < 0.05). Post-procedural cTnI elevation was significantly less frequent among patients in the upstream tirofiban group compared with the HDB tirofiban and abciximab groups (9.4% vs. 30% vs. 38.7%, respectively; p = 0.018). The cTnI levels after PCI were significantly lower with upstream tirofiban compared with HDB tirofiban (3.8 +/- 4.1 vs. 7.2 +/- 12; p = 0.015) and abciximab (3.8 +/- 4.1 vs. 9 +/- 13.8; p = 0.0002)

CONCLUSIONS: Among high-risk non-ST-segment-elevation ACS patients treated with an early invasive strategy, upstream tirofiban is associated with improved tissue-level perfusion and attenuated myocardial damage.