Downloaded from http://jnis.bmj.com/ on April 23, 2015 - Published by group.bmj.com
Commentary
Game changer for endovascular treatment of acute ischemic stroke? Marc I Chimowitz Although there has been great hope that endovascular treatment would improve the outcome of patients with acute ischemic stroke, current data from completed randomized trials have failed to provide evidence that endovascular treatment is superior to medical treatment.1–3 These trials, however, have been criticized for poor patient selection, delay from stroke onset to initiation of endovascular treatment and limited success in achieving adequate revascularization of occluded intracranial arteries with the firstgeneration devices used in these trials.4 To establish that endovascular therapy is more effective than medical treatment in subgroups of patients with acute ischemic stroke in future trials, progress will need to be made on all three of these fronts. Some progress has already been made in refining patient selection criteria and instituting programs to reduce the time from stroke onset to initiation of treatment,5 but the most remarkable progress has been made in improving revascularization with newer devices. In previous randomized trials with first-generation devices, the limited success in revascularization was attributed to one or more of the following: high rate of failure to achieve recanalization; long duration from groin puncture to revascularization; or inadequate restoration of sufficient antegrade flow. Two subsequent randomized trials (SWIFT6 and TREVO 27) evaluating newer devices, the stent retrievers, showed that these devices were significantly more effective for improving revascularization and patient outcome at 90 days compared with a first-generation device (the Merci retriever). In the SWIFT trial the mean time from symptom onset to arterial puncture was close to 5 h and the median (IQR) time from initial placement of the guide catheter (not groin puncture) to achievement of recanalization or end of the procedure was 36 min (18–65 min) with the stent retriever and 52 min (31–73 min) with the Merci device. Successful recanalization (defined as the achievement of Thrombolysis In Correspondence to Dr Marc I Chimowitz, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29435, USA; [email protected] 252
Myocardial Ischemia (TIMI) scale 2 or 3 flow in all treatable vessels) with the study device alone was attained in 69% of patients treated with the stent retriever and in 30% of patients treated with the Merci device, as determined by the core laboratory (per site readings, these success rates were 83% and 48%, respectively). Successful recanalization at the end of the procedure, including the use of adjunctive endovascular treatments, was achieved in 89% of patients in the stent retriever arm and in 67% of patients in the Merci arm based on site readings.6 In the TREVO 2 trial the mean time from symptom onset to arterial puncture was 4.5–4.6 h and the mean time to a Thrombolysis In Cerebral Infarction (TICI) reperfusion score ≥2 (ie, 2a, 2b or 3) or the end of the procedure was 47.8 min with the stent retriever and 47.3 min with the Merci device. Based on core laboratory readings, 86% of patients treated with the stent retriever and 60% of patients treated with the Merci device achieved a TICI score of ≥2 (the corresponding percentages based on site readings were 85% and 66%, respectively). Successful reperfusion at the end of the procedure, including the use of adjunctive treatments, was achieved in 92% of patients in the stent retriever arm and in 77% of patients in the Merci arm based on core laboratory readings. A TICI score of 2b or 3, which is now considered the technical standard of successful revascularization, was achieved in 68% of patients treated with the stent retriever and in 44% of patients treated with the Merci device as measured by the core laboratory.7 Turk and colleagues report a new endovascular technique that achieved an unprecedented rate of revascularization of occluded intracranial arteries in a series of 98 patients presenting with acute ischemic stroke at six centers.8 This endovascular treatment involves a direct aspiration firstpass technique (coined ADAPT) using new-generation flexible large-bore aspiration catheters inserted to the face of the thrombus to achieve revascularization of the occluded intracranial artery. If the aspiration technique fails, stent retrievers can be inserted through the large-bore catheters to attempt revascularization. Using this sequential approach, the authors were able to revascularize the
occluded intracranial artery and achieve TICI 2b or 3 flow 95% of the time (based on site readings) at a mean time of 36.6 min after groin puncture. The aspiration component alone achieved successful revascularization in 78% of patients at a mean time of 31.6 min, but in the additional 17% of patients in whom an adjunctive device was successfully used to recanalize the artery, the mean time to revascularization was almost double (56.8 min). Although initiation of endovascular treatment occurred on average 8.5 h after symptom onset and the mean NIH Stroke Scale score was 17.2 on presentation, 40% of patients had a modified Rankin Scale score of 0–2 at 90 days. These exciting results will inevitably lead to inferences that this technique is superior to other new endovascular devices, as well as claims of superior efficacy of this endovascular therapy over medical therapy, but it is important to remember that this was an uncontrolled study without central evaluation of angiograms or clinical endpoints by blinded adjudicators. Proof of superiority of this technique over other devices and of newer endovascular treatments over medical therapy will require randomized trials, several of which are ongoing.9 Undoubtedly, the substantial improvement in time to recanalization and the much higher rates of complete or near complete revascularization with ADAPT and other new devices provide endovascular therapy with the best chance yet to fulfill its promise as an important treatment for lowering morbidity after acute ischemic stroke. As physicians treating patients with acute ischemic stroke, we have an important responsibility to complete the ongoing randomized trials as soon as possible,9 hopefully with definitive evidence emerging from these trials establishing that better outcomes can be achieved with the new endovascular devices in well selected patients than with currently available medical therapy which leaves far too many patients with substantial disability after stroke. Competing interests The author has received the following grant support from NIH/NINDS for research related to the secondary prevention of stroke in patients with intracranial arterial stenosis: the WASID Trial (R01 NS36643), the NIH Wingspan Registry (R01 NS051688), the SAMMPRIS Trial (U01 NS058728) and a K24 grant (K24 NS050307). Corporate support for this research has consisted of Bayer providing aspirin and placebo aspirin for the WASID trial, Bristol-Myers Squibb supplying warfarin and placebo warfarin for the WASID trial, Stryker Neurovascular (formerly Boston Scientific Neurovascular) providing study devices and supplemental funding for third party device distribution, site monitoring and study auditing in the SAMMPRIS trial, and the Investigator-Sponsored Study Program of AstraZeneca that donated rosuvastatin (Crestor) to study patients in SAMMPRIS. Chimowitz MI. J NeuroIntervent Surg May 2014 Vol 6 No 4
Downloaded from http://jnis.bmj.com/ on April 23, 2015 - Published by group.bmj.com
Commentary Provenance and peer review Commissioned; internally peer reviewed.
J NeuroIntervent Surg 2014;6:252–253. doi:10.1136/neurintsurg-2014-011187 6
REFERENCES 1
2
To cite Chimowitz MI. J NeuroIntervent Surg 2014;6:252–253. Received 24 February 2014 Accepted 26 February 2014 Published Online First 12 March 2014
3
4
5
▸ http://dx.doi.org/10.1136/neurintsurg-2014-011125
Broderick JP, Palesch YY, Demchuk AM, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013;368:893–903. Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013;368:904–13. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 2013;368:914–23. Nogueira RG, Gupta R, Dávalos A. IMS-III and SYNTHESIS expansion trials of endovascular therapy in acute ischemic stroke: how can we improve? Stroke 2013;44:3272–4. Saver JL, Jovin TG, Smith WS, et al. Stroke treatment academic industry roundtable: research priorities in the
7
8
9
assessment of neurothrombectomy devices. Stroke 2013;44:3596–601. Saver JL, Jahan R, Levy EI, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 2012;380:1241–9. Nogueira RG, Lutsep HL, Gupta R, et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet 2012;380: 1231–40. Turk AS, Frei D, Fiorella D, et al. ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy. J NeuroIntervent Surg 2014;6:260–4. Goyal M, Shamy M, Menon BK, et al. Endovascular stroke trials: why we must enroll all eligible patients. Stroke 2013;44:3591–5.
Scan here to listen to a podcast with Marc Chimowitz on this article
Chimowitz MI. J NeuroIntervent Surg May 2014 Vol 6 No 4
253
Downloaded from http://jnis.bmj.com/ on April 23, 2015 - Published by group.bmj.com
Game changer for endovascular treatment of acute ischemic stroke? Marc I Chimowitz J NeuroIntervent Surg 2014 6: 252-253 originally published online March 12, 2014
doi: 10.1136/neurintsurg-2014-011187 Updated information and services can be found at: http://jnis.bmj.com/content/6/4/252
These include:
References Email alerting service
This article cites 8 articles, 3 of which you can access for free at: http://jnis.bmj.com/content/6/4/252#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Commentary
Game changer for endovascular treatment of acute ischemic stroke? Marc I Chimowitz Although there has been great hope that endovascular treatment would improve the outcome of patients with acute ischemic stroke, current data from completed randomized trials have failed to provide evidence that endovascular treatment is superior to medical treatment.1–3 These trials, however, have been criticized for poor patient selection, delay from stroke onset to initiation of endovascular treatment and limited success in achieving adequate revascularization of occluded intracranial arteries with the firstgeneration devices used in these trials.4 To establish that endovascular therapy is more effective than medical treatment in subgroups of patients with acute ischemic stroke in future trials, progress will need to be made on all three of these fronts. Some progress has already been made in refining patient selection criteria and instituting programs to reduce the time from stroke onset to initiation of treatment,5 but the most remarkable progress has been made in improving revascularization with newer devices. In previous randomized trials with first-generation devices, the limited success in revascularization was attributed to one or more of the following: high rate of failure to achieve recanalization; long duration from groin puncture to revascularization; or inadequate restoration of sufficient antegrade flow. Two subsequent randomized trials (SWIFT6 and TREVO 27) evaluating newer devices, the stent retrievers, showed that these devices were significantly more effective for improving revascularization and patient outcome at 90 days compared with a first-generation device (the Merci retriever). In the SWIFT trial the mean time from symptom onset to arterial puncture was close to 5 h and the median (IQR) time from initial placement of the guide catheter (not groin puncture) to achievement of recanalization or end of the procedure was 36 min (18–65 min) with the stent retriever and 52 min (31–73 min) with the Merci device. Successful recanalization (defined as the achievement of Thrombolysis In Correspondence to Dr Marc I Chimowitz, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29435, USA; [email protected] 252
Myocardial Ischemia (TIMI) scale 2 or 3 flow in all treatable vessels) with the study device alone was attained in 69% of patients treated with the stent retriever and in 30% of patients treated with the Merci device, as determined by the core laboratory (per site readings, these success rates were 83% and 48%, respectively). Successful recanalization at the end of the procedure, including the use of adjunctive endovascular treatments, was achieved in 89% of patients in the stent retriever arm and in 67% of patients in the Merci arm based on site readings.6 In the TREVO 2 trial the mean time from symptom onset to arterial puncture was 4.5–4.6 h and the mean time to a Thrombolysis In Cerebral Infarction (TICI) reperfusion score ≥2 (ie, 2a, 2b or 3) or the end of the procedure was 47.8 min with the stent retriever and 47.3 min with the Merci device. Based on core laboratory readings, 86% of patients treated with the stent retriever and 60% of patients treated with the Merci device achieved a TICI score of ≥2 (the corresponding percentages based on site readings were 85% and 66%, respectively). Successful reperfusion at the end of the procedure, including the use of adjunctive treatments, was achieved in 92% of patients in the stent retriever arm and in 77% of patients in the Merci arm based on core laboratory readings. A TICI score of 2b or 3, which is now considered the technical standard of successful revascularization, was achieved in 68% of patients treated with the stent retriever and in 44% of patients treated with the Merci device as measured by the core laboratory.7 Turk and colleagues report a new endovascular technique that achieved an unprecedented rate of revascularization of occluded intracranial arteries in a series of 98 patients presenting with acute ischemic stroke at six centers.8 This endovascular treatment involves a direct aspiration firstpass technique (coined ADAPT) using new-generation flexible large-bore aspiration catheters inserted to the face of the thrombus to achieve revascularization of the occluded intracranial artery. If the aspiration technique fails, stent retrievers can be inserted through the large-bore catheters to attempt revascularization. Using this sequential approach, the authors were able to revascularize the
occluded intracranial artery and achieve TICI 2b or 3 flow 95% of the time (based on site readings) at a mean time of 36.6 min after groin puncture. The aspiration component alone achieved successful revascularization in 78% of patients at a mean time of 31.6 min, but in the additional 17% of patients in whom an adjunctive device was successfully used to recanalize the artery, the mean time to revascularization was almost double (56.8 min). Although initiation of endovascular treatment occurred on average 8.5 h after symptom onset and the mean NIH Stroke Scale score was 17.2 on presentation, 40% of patients had a modified Rankin Scale score of 0–2 at 90 days. These exciting results will inevitably lead to inferences that this technique is superior to other new endovascular devices, as well as claims of superior efficacy of this endovascular therapy over medical therapy, but it is important to remember that this was an uncontrolled study without central evaluation of angiograms or clinical endpoints by blinded adjudicators. Proof of superiority of this technique over other devices and of newer endovascular treatments over medical therapy will require randomized trials, several of which are ongoing.9 Undoubtedly, the substantial improvement in time to recanalization and the much higher rates of complete or near complete revascularization with ADAPT and other new devices provide endovascular therapy with the best chance yet to fulfill its promise as an important treatment for lowering morbidity after acute ischemic stroke. As physicians treating patients with acute ischemic stroke, we have an important responsibility to complete the ongoing randomized trials as soon as possible,9 hopefully with definitive evidence emerging from these trials establishing that better outcomes can be achieved with the new endovascular devices in well selected patients than with currently available medical therapy which leaves far too many patients with substantial disability after stroke. Competing interests The author has received the following grant support from NIH/NINDS for research related to the secondary prevention of stroke in patients with intracranial arterial stenosis: the WASID Trial (R01 NS36643), the NIH Wingspan Registry (R01 NS051688), the SAMMPRIS Trial (U01 NS058728) and a K24 grant (K24 NS050307). Corporate support for this research has consisted of Bayer providing aspirin and placebo aspirin for the WASID trial, Bristol-Myers Squibb supplying warfarin and placebo warfarin for the WASID trial, Stryker Neurovascular (formerly Boston Scientific Neurovascular) providing study devices and supplemental funding for third party device distribution, site monitoring and study auditing in the SAMMPRIS trial, and the Investigator-Sponsored Study Program of AstraZeneca that donated rosuvastatin (Crestor) to study patients in SAMMPRIS. Chimowitz MI. J NeuroIntervent Surg May 2014 Vol 6 No 4
Downloaded from http://jnis.bmj.com/ on April 23, 2015 - Published by group.bmj.com
Commentary Provenance and peer review Commissioned; internally peer reviewed.
J NeuroIntervent Surg 2014;6:252–253. doi:10.1136/neurintsurg-2014-011187 6
REFERENCES 1
2
To cite Chimowitz MI. J NeuroIntervent Surg 2014;6:252–253. Received 24 February 2014 Accepted 26 February 2014 Published Online First 12 March 2014
3
4
5
▸ http://dx.doi.org/10.1136/neurintsurg-2014-011125
Broderick JP, Palesch YY, Demchuk AM, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013;368:893–903. Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013;368:904–13. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 2013;368:914–23. Nogueira RG, Gupta R, Dávalos A. IMS-III and SYNTHESIS expansion trials of endovascular therapy in acute ischemic stroke: how can we improve? Stroke 2013;44:3272–4. Saver JL, Jovin TG, Smith WS, et al. Stroke treatment academic industry roundtable: research priorities in the
7
8
9
assessment of neurothrombectomy devices. Stroke 2013;44:3596–601. Saver JL, Jahan R, Levy EI, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 2012;380:1241–9. Nogueira RG, Lutsep HL, Gupta R, et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet 2012;380: 1231–40. Turk AS, Frei D, Fiorella D, et al. ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy. J NeuroIntervent Surg 2014;6:260–4. Goyal M, Shamy M, Menon BK, et al. Endovascular stroke trials: why we must enroll all eligible patients. Stroke 2013;44:3591–5.
Scan here to listen to a podcast with Marc Chimowitz on this article
Chimowitz MI. J NeuroIntervent Surg May 2014 Vol 6 No 4
253
Downloaded from http://jnis.bmj.com/ on April 23, 2015 - Published by group.bmj.com
Game changer for endovascular treatment of acute ischemic stroke? Marc I Chimowitz J NeuroIntervent Surg 2014 6: 252-253 originally published online March 12, 2014
doi: 10.1136/neurintsurg-2014-011187 Updated information and services can be found at: http://jnis.bmj.com/content/6/4/252
These include:
References Email alerting service
This article cites 8 articles, 3 of which you can access for free at: http://jnis.bmj.com/content/6/4/252#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
