Current Issues in IV Thrombolysis

초록

Since the pivotal NINDS rtPA trial in 1996, intravenous(IV) tPA has been the mainstream treatment of acute ischemic treatment, even in these era of endovascular thrombectomy. Its indication and regimen has been almost standardized after many trials and errors, but it is still evolving its scope in diverse clinical situation. Application of IV tPA to minor or non-disabling stroke has long been a subject of debate. Recent study (PRISM) shows little benefit in this situation. Regarding the optimal dose of IV tPA, though ended as negative trial, ENCHANTED study showed no clear superiority of standard 0.9 over reduced 0.6mg/kg dose. Recent trials tested the application of IV tPA for the wake-up or unclear onset stroke (WAKE-UP, THAWS) or for >4.5h with favorable multimodal imaging profile (ECASS IV, EXTEND) with some positive results, casting some possibility of switch from time-based to tissue-based indication of IV thrombolysis. Sometimes, IV thrombolysis before endovascular thrombectomy seems to delay the groin puncture time with no additional benefit, and the effect of this bridging thrombolysis is doubted and investigated. (DIRECT-SAFE) The result might influence the long lasting debate between mother-ship vs. drip-and-ship model of stroke center organization. TPA has long been a lone player in the IV thrombolysis, but recently it faces a powerful challenger, TNK-tPA. With its favorable pharmacokinetic and pharmacodynamic profiles, TNK-tPA showed promising result compared to TPA in previous trials, and several parallel trials with TNK-tPA are currently ongoing. (TASTE, TEMPO, TWIST) The result of these trials might have potential of replacing tPA with TNK-tPA in the near future.