Is there still a role for intravenous thrombolysis in the era of mechanical thrombectomy in patients with acute intracranial large artery occlusions?

Abstract

At the beginning of 2015 several randomized controlled trials (RCTs) showed, beyond a shadow of doubt, that mechanical thrombectomy was highly effective in patients with acute proximal intracranial arterial occlusions. This development has dramatically changed the management of acute ischaemic stroke. After the initial deception in 2013, when three neutral RCTs were published, mechanical thrombectomy is now considered the main treatment option in acute large intracranial vessel occlusions with or without intravenous thrombolysis (IVT) [1]. The next question is whether IVT can be skipped in these patients. Although a clear answer to this question is lacking, this approach of primary thrombectomy is already being implemented by some stroke physicians and neuro-interventionists. A parallel is being drawn with the treatment of acute myocardial infarction, where the IVT has been completely abandoned and primary percutaneous coronary intervention (PCI) is the first treatment option [2]. In this issue of the European Journal of Neurology, Feda and colleagues report a single center experience about the impact and significance of IVT in an academic stroke center in Germany [3]. They demonstrated that, even in a very well equipped comprehensive stroke center, IVT is still frequently offered to patients with proximal arterial occlusions. In more than 80% of the patients without clear contraindications for IVT, the treatment was given with good clinical outcomes. This message from the authors is important for several reasons. Although IVT appears to be less effective in recanalizing larger clots, there are several good reasons to still administer recombinant tissue plasminogen activator before thrombectomy [4]. Recanalization alone is not the primary goal, but reducing the degree of disability is the most important outcome measure. In several post hoc analyses of trial data and large cohort studies, IVT has been shown to be effective in patients with high baseline National Institutes of Health Stroke Scale scores in terms of reducing disability [5–7]. Approximately 8% of the patients with proximal cerebral arterial occlusions have already sufficient recanalization before the start of mechanical thrombectomy [8]. With the recent data about tenecteplase, an alternative and more specific fibrinolytic agent, this percentage can increase even up to 22%. In these patients, skipping IVT would necessitate mechanical thrombectomy, a more invasive and expensive treatment option than IVT alone [9]. One of the possible advantages of skipping IVT is to prevent devastating (intracranial) hemorrhagic complications. But when comparing the current available data, there is no decreased incidence of symptomatic intracerebral hemorrhage in the group that underwent primary mechanical thrombectomy compared to the IVT and adjunctive mechanical thrombectomy group [10,11]. The comparison being made with primary PCI for myocardial infarction, based on a pathophysiological point of view, is incorrect. Acute myocardial infarction is usually caused by a plaque rupture that acutely occludes the vessel and may necessitate placement of a permanent stent, because IVT is not able to recanalize a ruptured plaque. In the western world, intracranial arterial occlusions are most commonly caused by emboli from cardiac sources or from large vessel atherosclerosis of the cervical arteries and benefit from IVT after fibrinolysis of the clot. Moreover IVT could theoretically enhance the mechanical thrombectomy by recanalizing smaller arteries and dissolving distal emboli after mechanical proximal clot removal. There are ongoing RCTs, such as MR CLEAN NOIV (ISRCTN80619088), DIRECT-MT (NCT03469206) and the SWIFT-DIRECT (NCT03192332) that make a head to head comparison of IVT and mechanical thrombectomy against mechanical thrombectomy alone. Until these trials demonstrate a clear benefit from primary mechanical thrombectomy above the combined approach, every stroke patient deserves the most optimal treatment that includes IVT in the absence of clear contraindications. The study from