Thrombolysis Before Thrombectomy in Acute Large Vessel Occlusion: a Risk/Benefit Assessment and Review of the Evidence

Abstract

Recent evidence has shown an overwhelming benefit of mechanical thrombectomy for acute anterior circulation large vessel occlusion (LVO). Whether there is any additional benefit of IV tPA treatment prior to thrombectomy over thrombectomy alone is unproven in randomized trials. In this review, we summarize the available evidence for and against pre-thrombectomy treatment with IV tPA. In clinical trials demonstrating efficacy of thrombectomy, the majority of included patients were eligible for (and treated with) IV tPA. Systemic thrombolysis prior to thrombectomy is fraught with potential disadvantages: delay in thrombectomy, increased risk of systemic hemorrhagic complications and angioedema, and limitation of endovascular treatment options in patients who require more vigorous antithrombotic treatment (for instance due to stent placement). Two randomized clinical trials comparing outcomes of patients treated with IV tPA + thrombectomy versus thrombectomy alone have recently reported their outcomes. The DIRECT-MT investigators found no difference in functional outcomes or mortality among patients pre-treated with IV tPA prior to thrombectomy, while the SKIP investigators found similar rates of good functional outcome and mortality between treatment groups--although they failed to demonstrate non-inferiority. The limitations of these trials are reviewed here. Therefore, much of our understanding relies on indirect comparisons between patient groups, whereby patients treated with IV tPA + thrombectomy were compared with IV tPA-ineligible patients who underwent thrombectomy alone. Limited meta-analysis data suggest equipoise between combination therapy over a direct-to-thrombectomy approach for patients with acute LVO who meet criteria for IV tPA. Further confounding the picture is the emergence of IV tenecteplase as a potentially superior alternative to alteplase as a pre-thrombectomy systemic lytic agent in patients with LVO. While thrombectomy offers a more effective means of reperfusion in acute LVO compared with IV tPA alone, definitive evidence is lacking that thrombectomy without prior IV thrombolysis is equivalent (or superior) to thrombectomy preceded by IV tPA. While recent trial evidence has suggested non-inferiority of direct MT, given that IV thrombolysis has been established as a standard of care in acute ischemic stroke, IV tPA should be given in all eligible patients with disabling deficits for whom thrombectomy is not immediately available. Results of further, ongoing randomized trials will hopefully clarify what (if any) additional benefit there is for intravenous thrombolysis prior to thrombectomy, in what subgroups (if any) withholding IV thrombolysis prior to MT is beneficial, and furthermore, which agent (alteplase or tenecteplase) is the optimal drug for this indication.