Patient selection for i.v. thrombolysis and thrombectomy

Transcription

1 3 rd Congress of the European Academy of Neurology Amsterdam, The Netherlands, June 24 27, 2017 Teaching Course 8 Acute treatment and early secondary prevention of stroke Level 2 Patient selection for i.v. thrombolysis and thrombectomy Urs Fischer Bern, Switzerland Urs.Fischer@insel.ch

2 2015 has become the year of the big breakthrough in the history of modern stroke treatment: in the first few months of 2015 more positive stroke trials were published than in the last 20 years before. Eight randomized controlled trials have now consistently shown that endovascular stroke treatment in combination with best medical treatment is superior to best medical treatment alone in patients with an acute occlusion of the internal carotid artery or the main stem of the middle cerebral artery. After the publication of the NINDS trial in 1995, which proofed the efficacy of intravenous thrombolysis with rt-pa in patients with an acute ischemic stroke within 3 hours after symptom onset major positive trials in acute stroke treatment were lacking. The ECASS III Trial showed in 1998, that rt-pa is also effective 3 to 4.5 hours after symptom onset and the PROACT II Trial proofed in 1999, that intra-arterial Pro-Urokinase improves outcome in stroke patients with an acute occlusion of the main stem of the middle cerebral artery. Nevertheless Pro-Urokinase was not approved by the FDA due to few patients and marginal significance. 1

3 Many physicians have observed that outcome in stroke patients can be approved if immediate vessel recanalization can be achieved. However recanalization rates after intravenous thrombolysis in patients with proximal vessel occlusion are not higher than 30-40%. Pioneers of acute endovascular stroke treatment performed the first endovascular procedure in Switzerland in 1992 and they showed with their team in many nonrandomized studies that recanalization rates and outcome in patients with proximal vessel occlusion are significantly better after endovascular stroke treatment than after intravenous thrombolysis alone. The clinical effect of acute stroke treatment is often obvious: stroke patients arrive with a severe neurological deficit and sometimes show a significant improvement in the angiography suite immediately after vessel recanalization. Some of these patients are even able to go home after a few days. Despite these evident clinical results the efficacy of endovascular stroke treatment could not be proven for many years. Even in 2013 three randomized controlled trial on endovascular stroke treatment (i.e. IMS III, MR RESCUE, SYNTHESIS) showed no benefit of endovascular stroke treatment compared to intravenous thrombolysis. However these trials had many methodological issues: the majority of patients were treated with first-generation endovascular devices with low recanalization rates, the time window from symptom onset to revascularization was substantial and - most importantly - vessel imaging prior to randomization was not mandatory. The important breakthrough came with new endovascular devices (i.e. stent retrievers). Currently there are 8 published randomized controlled trials (MR CLEAN; REVASCAT; ESCAPE; EXTEND-IA; SWIFT PRIME; THRACE; THERAPY; PISTE) i,ii,iii,iv,v, which compared stroke patients with best 2

4 medical treatment (majority with rt-pa) and best medical plus endovascular treatment (most patients were treated with stent-retrievers). Recanalization rates after endovascular therapy were significantly higher than in the control group and more patients survived in the endovascular group without a relevant handicap. According to an individual patient data metaanalysis of five trials the number needed to treat was 2.6. The unanswered questions Despite this major breakthrough many issues in acute stroke treatment are still unresolved: How to increase stroke care in Europe? According to a recent ESO ESMINT EAN SAFE survey on acute stroke treatment in Europe there are still many regions in Europe where intravenous thrombolysis and endovascular therapy is still unavailable for the majority of stroke patients. Therefore efforts have to be done to increase the number of stroke units, intravenous thrombolysis and endovascular stroke therapy. How to select the right patient for endovascular stroke treatment? In the above mentioned trials patients with unknown time of symptom onset and those arriving in the stroke center more than 6 hours after symptom onset were excluded. The DAWN trial, presented at ESOC 2017 showed, that patients after 6 hours with a mismatch have a major benefit from endovascular treatment with a number needed to treat of 2.8 (paper not yet published). Advanced imaging is likely to play an important role in patients with unclear time of symptom onset. According to the pivotal trials endovascular stroke treatment seems also to be effective in the 3

5 elderly even though outcome is generally worse in these patients than in younger patients. Is bridging therapy necessary? Whether treatment with iv t-pa prior to mechanical clot retrieval in patients with large artery anterior circulation stroke is of any benefit is currently one of the most important unanswered questions in acute stroke management. A randomized trial comparing direct mechanical thrombectomy with bridging therapy will solve this question and is currently planned. Is endovascular stroke treatment also effective in basilar artery occlusions? In the above mentioned trials patients with occlusions of the basilar artery were excluded. Whether endovascular stroke treatment is effective in these patients is still unproven. Is endovascular stroke treatment also effective in tandem occlusions? Patients with an acute occlusion of the extracranial internal carotid artery in combination with an acute intracranial occlusion were excluded in most trials. Even though the benefit of endovascular stroke treatment in these patients is very likely the final proof by a randomized controlled trial is still missing. Conscious sedation or general anesthesia? Endovascular procedures can be performed by conscious sedation or general anesthesia. Several trials suggest that conscious sedation and general anesthesia are equally effective. 4

6 Which device should be used? It is still unknown whether some devices are superior than others and whether proximal protection devices are beneficial to prevent thrombus fragmentation and distal embolization of thrombi. However most patients in the above mentioned trials were treated with the Solitaire device. But head-to head comparisons of different devices are lacking. Conclusions: Endovascular stroke therapy is now the standard of care in patients with acute occlusions of main arteries in the anterior circulation. Patients with an occlusion of smaller vessels should be immediately treated with intravenous thrombolysis. All stroke patients should have immediate access to a stroke units and stroke center with the possibility for intravenous and endovascular stroke treatment. Even though there was a major breakthrough in acute stroke treatment in 2015 many issues in the management of acute stroke treatment are still unresolved. After this major breakthrough we have to start to answer the unanswered questions. Disclosure: Urs Fischer is Principal Investigator of the ELAN, SWIFT DIRECT and the SWITCH trial and he is a consultant for Covidien (Medtronic). 5

7 References: 1. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372: Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372: Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, et al. Endovascular therapy for ischemic stroke with perfusionimaging selection. N Engl J Med 2015;372: Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al. Stent-Retriever Thrombectomy after Intravenous t-pa vs. t-pa Alone in Stroke. N Engl J Med 2015:372: Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, et al. Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke. N Engl J Med 2015:372: