Background Limited post-marketing data exist on the use of the Solitaire FR device in clinical practice. The North American Solitaire Stent Retriever Acute Stroke (NASA) registry aimed to assess the real world performance of the Solitaire FR device in contrast with the results from the SWIFT (Solitaire with the Intention for Thrombectomy) and TREVO 2 (Trevo versus Merci retrievers for thrombectomy revascularization of large vessel occlusions in acute ischemic stroke) trials.
Methods The investigator initiated NASA registry recruited North American sites to submit retrospective angiographic and clinical outcome data on consecutive acute ischemic stroke (AIS) patients treated with the Solitaire FR between March 2012 and February 2013. The primary outcome was a Thrombolysis in Myocardial Ischemia (TIMI) score of ≥2 or a Treatment in Cerebral Infarction (TICI) score of ≥2a. Secondary outcomes were 90 day modified Rankin Scale (mRS) score, mortality, and symptomatic intracranial hemorrhage.
Results 354 patients underwent treatment for AIS using the Solitaire FR device in 24 centers. Mean time from onset to groin puncture was 363.4±239 min, mean fluoroscopy time was 32.9±25.7 min, and mean procedure time was 100.9±57.8 min. Recanalization outcome: TIMI ≥2 rate of 83.3% (315/354) and TICI ≥2a rate of 87.5% (310/354) compared with the operator reported TIMI ≥2 rate of 83% in SWIFT and TICI ≥2a rate of 85% in TREVO 2. Clinical outcome: 42% (132/315) of NASA patients demonstrated a 90 day mRS ≤2 compared with 37% (SWIFT) and 40% (TREVO 2). 90 day mortality was 30.2% (95/315) versus 17.2% (SWIFT) and 29% (TREVO 2).
Conclusions The NASA registry demonstrated that the Solitaire FR device performance in clinical practice is comparable with the SWIFT and TREVO 2 trial results.
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Mechanical thrombectomy for acute ischemic stroke (AIS) has shown significant technical advances in the past 5 years.1–5 In light of the negative results of the Interventional Management of Stroke III (IMS-III), the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and the Local versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS) trials for endovascular treatment of AIS,6–8 the recent results of the Solitaire with the Intention for Thrombectomy (SWIFT) and the Trevo versus Merci retrievers for thrombectomy revascularization of larger vessel occlusions in acute ischemic stroke (TREVO 2) randomized trials for AIS demonstrated significantly better recanalization rates and good clinical outcomes with the Solitaire FR (Covidien, EV3 Neurovascular, Irvine, California, USA) and Trevo (Stryker Neurovascular, Mountain View, California, USA) devices compared with the Merci retriever (Stryker Neurovascular)4 ,5 within 8 h of symptom onset. Although the results of SWIFT and TREVO 2 are promising, industry sponsored clinical trials have strict inclusion and exclusion criteria and specific time windows, which may limit the generalizability of these results. Therefore, it becomes critical to duplicate the trial results in clinical practice, independent of the device manufacturer and sponsors. Replication of these results by different investigators will provide stronger evidence to support the efficacy and safety profile of the device. In addition, prior to introducing new thrombectomy devices in randomized clinical efficacy trials, it is of paramount importance to demonstrate device performance consistency across different clinical centers and operators. Large post-marketing independent studies allow further exploratory analysis of device performance and technical nuances that may provide invaluable data to guide the design of future AIS endovascular therapy clinical trials.
Limited data exist on the use of the Solitaire FR device in real world clinical practice following its approval by the Food and Drug Administration in March of 2012. The North American Solitaire Acute Stroke (NASA) registry, the largest post-marketing study to date, aimed to assess the real world revascularization performance, safety, and clinical efficacy of the Solitaire FR device in comparison with the results from the SWIFT and TREVO 2 clinical trials.
The investigator initiated NASA retrospective registry recruited 24 clinical sites within North America to submit demographic, clinical presentation, procedural, technical, site adjudicated angiographic, and clinical outcome data on consecutive AIS patients treated with the Solitaire FR device between March 2012 and February 2013. All patients in the NASA registry received the Solitaire FR device as the first choice device to restore blood flow. The data were stored and analyzed by the central coordinating site, the Medical College of Wisconsin. This study was performed without industry sponsorship or funding. Institutional review board approval was obtained from each institution's review board; only de-identified information was submitted for analysis.
Primary outcome success was defined as achieving a Thrombolysis in Myocardial Ischemia (TIMI) score of ≥2 or a Treatment in Cerebral Infarction (TICI) score of ≥2a (as defined by the SWIFT and TREVO 2 trial definitions, respectively4 ,5 ,9), as documented on the angiogram at the end of the procedure or prior to the use of rescue therapy.
Secondary outcomes were symptomatic intracranial hemorrhage (sICH) on the 24 h follow-up head CT, modified Rankin Scale (mRS) score, and mortality at 90 days. sICH was defined as any parenchymal hematoma, subarachnoid hemorrhage, or intraventricular hemorrhage associated with worsening of the National Institutes of Health Stroke Scale (NIHSS) score by ≥4 within 24 h.
Baseline characteristics and demographic data were analyzed and contrasted with the SWIFT and TREVO 2 patients. Fisher exact or χ2 tests were used for categorical variables and the Student's t test/F test for continuous variables. Revascularization and clinical outcome data were also compared between the NASA, SWIFT, and TREVO 2 cohorts. Statistical significance was set at p<0.05. Statistical analyzes were performed using JMP V.10 (SAS institute, Cary, North Carolina, USA).
Demographic and baseline data
The NASA post-marketing registry enrolled 354 consecutive AIS patients treated with the Solitaire FR device as a first pass and treatment choice. Demographic and baseline characteristics are shown in table 1 for the NASA, SWIFT, and TREVO 2 groups. No difference was observed in baseline age between the cohorts (mean age of 67.3 vs 67.1 vs 67.4 years in the NASA, SWIFT, and TREVO 2 groups, respectively) with all groups almost equally divided between genders. The mean NIHSS at presentation was 18.1 in the NASA group compared with 17.3 and 18.3 in the SWIFT and TREVO 2 groups, respectively. In the NASA cohort, a larger proportion of patients with basilar occlusions were treated (10.2%), compared with 2% and 8% in the SWIFT and TREVO 2 groups, respectively. Mean time from symptom onset to groin puncture was longer in the NASA group, at 363.4 min, versus 301.6 and 276 min in the SWIFT and TREVO 2 groups, respectively. Mean time to revascularization or end of procedure was longer in the NASA population compared with the SWIFT trial (50 vs 36 min, respectively) and median time to revascularization was 77 min in the NASA cohort compared with 47.8 min in the TREVO 2 trial (TREVO 2 reported median time only).
Revascularization and technical
In the NASA cohort, the TIMI ≥2 revascularization rate was 83.3%, which mirrored the operator adjudicated outcome in the SWIFT trial (83%) (table 2). The TICI ≥2a, ≥2b, and 3 revascularization rates were 87.5%, 72.5%, and 40.2% in the NASA group versus 85%, 68%, and 14% in the TREVO 2 group, respectively. Rescue therapy was used in 25.7% of NASA patients compared with 21% and 18% in the SWIFT and TREVO 2 groups, respectively. The number of passes was 2 or less in 76% of cases, and 3 or less in 94% of NASA cases.
The 90 day mRS score was available in 315/354 (89%) NASA patients. The overall rate of good clinical outcome at 90 days (defined as mRS ≤2) was 42% in the NASA cohort and 37% and 40% in the SWIFT and TREVO 2 trials, respectively (table 2). The 90 day mortality rate was 30.2% (NASA), 17.2% (SWIFT), and 29% (TREVO 2). The rate of sICH was 9.9% in the NASA cohort, and 2% and 4% in the SWIFT and TREVO 2 trials, respectively.
To date, the NASA registry is the largest independent investigator initiated study reporting the post-market use of the Solitaire FR device in the USA for the treatment of AIS patients with large intracranial vessel occlusions.
No difference in mean age or gender proportions was demonstrated between the NASA, SWIFT, and TREVO 2 cohorts. Mean NIHSS scores were not statistically different between the NASA, SWIFT, and TREVO 2 groups. Diabetes was less prominent in the NASA cohort compared with the TREVO 2 trial (25% vs 38%, respectively). All remaining baseline comorbidities were similar between the groups (table 1).
Time to groin puncture
Mean time from symptom onset to groin puncture was longer in the NASA registry than in the randomized trials, but similar to other stent retriever case studies.10 ,11 This was an anticipated finding in the NASA cohort as physicians tend to practice according to their local standards and may not follow the 8 h time window for treatment found in clinical trials. In this registry, investigators included patients treated outside the 8 h time window if imaging indicated a significant mismatch (per site investigator), worsening mild deficit on presentation, or posterior circulation strokes.
Vessel occlusion sites
The target vessels treated were similar in all cohorts, except for the posterior circulation, which was higher in the NASA registry (10.2%) compared with the SWIFT (2%) and TREVO 2 (8%) trials.4 ,5 A higher proportion of patients with posterior circulation strokes was also noted in two smaller post-marketing Solitaire FR registries.10 ,12 In clinical practice, physicians may treat a higher proportion of posterior circulation patients outside the traditional 8 h time window, due to the poor natural history of basilar artery occlusion. In the context of the SWIFT and TREVO 2 trials, these patients would have been excluded. Enrollment of more patients with posterior circulation strokes may also, in part, explain the longer time from symptom onset to groin puncture in the NASA registry compared with the SWIFT and TREVO 2 trials.
The site adjudicated revascularization results in the NASA registry were similar to the published results in the SWIFT and TREVO 2 trials (the reported site adjudicated results). TIMI ≥2 was achieved in 83.3% and 83% of patients in the NASA and SWIFT groups, respectively, while 87.5% of NASA and 85% TREVO 2 patients achieved TICI ≥2a. Our results reflect the consistent performance of the Solitaire FR device (and more generally stent retrievers) in clinical practice, as confirmed in previous case series.10–14 For example, in the US study of 102 patients, 88% achieved successful recanalization and 96% of 141 patients in the European Solitaire FR registry achieved a TICI score of ≥2a.10 ,12 In addition, the NASA registry results are consistent with the recent results of the prospective multicenter Solitaire FR Thrombectomy for Acute Revascularization (STAR) study in which 79.2% (160/202) of patients achieved successful revascularization (defined as TICI ≥2b, per core lab within three passes).15 While the overall rate of revascularization (TICI ≥2) may be close to those in the randomized trials, the rate of complete revascularization (TICI 3) was higher in the NASA group than the rate reported in the TREVO 2 trial (40.2% vs 14%) which may, in part, be related to site adjudication bias.5 A similar higher rate of TICI 3 was found in the European Solitaire FR registry of 37%, which was adjudicated by a core lab.12 This discrepancy in results might also be explained by increased operator experience and confidence, and the additional use of techniques, such as ‘lesional suction thrombectomy’ during retrieval, that may not be permitted in trials.
Time to revascularization
Time to revascularization was prolonged in this cohort compared with other clinical trials and registries, which may be related to inclusion of tandem lesions where proximal cervical intervention is necessary prior to intracranial thrombectomy. Another potential explanation is the lack of data in this registry on the exact timing of achieving successful revascularization (first attempt vs final revascularization result) or a consistent definition on end of the procedure timing.
A higher rate of rescue therapy use was observed in the NASA group (25.7%) compared with the SWIFT and TREVO 2 groups (21% and 18%, respectively). In real life practice, physicians tend to use more devices to achieve what they consider their optimal target revascularization outcome. In clinical trials, use of additional devices may be discouraged if the trial target revascularization end point is achieved. This may be, in part, related to lack of standardization in defining successful revascularization and what constitutes a meaningful and safe revascularization grade.16 ,17
The 90 day favorable clinical outcome rate, defined as an mRS score of ≤2, was 42% in the NASA registry compared with 37% and 40% in the SWIFT and TREVO 2 trials, respectively. Despite the longer time from symptom onset to puncture and a larger proportion of patients with posterior circulation strokes (10.2%) in the NASA registry, the rate of favorable clinical outcome was comparable with the SWIFT and TREVO 2 trial results. A similar finding was demonstrated in the European post-marketing study, where the rate of favorable outcome (mRS ≤2) was 55%.12
Intracranial hemorrhage in the NASA registry was higher than that observed in the prospective trials (9.9% vs 2% and 4% in the SWIFT and TREVO 2 trials, respectively). This may be explained, in part, by the difference in time to treatment from symptom onset and more liberal inclusion criteria in real life practice versus the stricter inclusion criteria in clinical trials, different patient selection criteria, perioperative management and differences in operative technique, as well as the higher proportion of rescue therapy use in NASA (25%) than in the SWIFT (21%) and TREVO 2 (18%) trials. A higher rate of sICH was also found in the European registry of 141 patients (4%) and in the US post-marketing experience (15%).10 ,12
Mortality in the NASA cohort (30.2%) was similar to the TREVO-2 trial (29%) but higher than in the SWIFT trial (17.2%).4 ,5 However, the rate of good clinical outcome was as good or better in the NASA registry. Several factors may explain the morality rate in this cohort, including heterogeneity between the groups, higher proportion of basilar occlusion, lack of age and NIHSS cut offs, and variability in the endovascular selection protocols across participating centers. In addition, in clinical trials, there may be a more rigorous level of clinical care and follow-up provided, as well as a higher threshold to implement life withdrawal measures. In the SWIFT and TREVO 2 trials, the difference in mortality may in part be explained by the difference in Alberta Stroke Program Early CT score distribution (>7 in 78% of the SWIFT group and in 50% of the TREVO 2 group). In the US experience of 101 patients, inhospital mortality was 26%, and 20% in the European experience of 141 patients.10 ,12
Data in the NASA registry were self-reported by the site investigator, and included a mixed group of retrospectively and prospectively followed patients. In addition, the NASA registry did not have a core imaging lab to adjudicate the cranial and vascular imaging, to confirm the rate of intracranial hemorrhage or recanalization. Finally, the rate of good clinical outcome was not universally blinded, and in some cases adjudicated from clinical notes or via telephone contact. Site adjudication bias may also overestimate favorable clinical outcome.
Although the NASA registry is not a direct comparator to the randomized SWIFT and TREVO 2 trials (due to differences in study design, etc),4 ,5 contrasting the main primary outcome measures with these trials is necessary to formulate an understanding of the performance of the device in real life practice. These data may provide valuable information that can guide future iterations of more efficient and safe devices to achieve higher rates of revascularization with a decreased number of passes, less time, and improve clinical outcomes. In addition, lessons learned from the post-marketing registries may be applied to the design of future clinical efficacy endovascular trials.
The NASA registry demonstrated the consistency of the Solitaire FR device performance in a post-marketing real life clinical practice, with high recanalization rates (87.5%) and favorable clinical outcome rates (42%) that were comparable with the results obtained in the SWIFT and TREVO 2 trials. In light of the negative results of the IMS-III, MR RESCUE, and SYNTHESIS trials for endovascular treatment of AIS,6 ,7 ,8 these promising and reproducible revascularization findings using a newer generation of stent retriever may influence clinical practice and guide the design of future endovascular AIS therapy trials.
Medical College of Wisconsin/Froedtert Hospital, Milwaukee, WI, Osama O Zaidat, Brian-Fred Fitzsimmons, John R Lynch, Marc A Lazzaro, Alicia C Castonguay, Mohammad Issa; Emory University School of Medicine, Atlanta, GA, Rishi Gupta, Raul G. Nogueira, Chung-Huan Johnny Sun; St. Luke's Kansas City, Kansas City, MO, Coleman O Martin, William E Holloway; Delray Medical Center, Delray Beach, FL, Nils Mueller-Kronast; California Pacific Medical Center, San Francisco, CA, Joey English; Nobl Barazangi, Christine Wong, Charlene Chen, Oana Spataru, Ann Bedenk, Megan Morrow, David Tong; Baptist Cardiac and Vascular Institute, Miami, FL, Italo Linfante, Guilherme Dabus, Eugene Lin, Edgar Samaniego; Alexian Brothers Medical Center, Elk Grove Village, IL, Tim W Malisch, Franklin Marden; Oregon Health and Science University, Portland, OR, Hormozd Bozorgchami; Wayne State University School of Medicine, Detroit, MI, Andrew Xavier; West Virginia University Hospital, Morgantown, WV, Ansaar Rai, Jennifer Domico; Vanderbilt University Medical Center, Nashville, TN, Michael T Froehler; University of Iowa, Iowa City, IA, Jeri Sieren, Heena Olalde; Provena Saint Joseph Medical Center, Joliet, IL, Aamir Badruddin; Boston Medical Center, Boston, MA, Thanh N Nguyen, Alexander M Norbash, Hesham Masoud, Judith Clark; Desert Regional Medical Center, Palm Springs, CA, Muhammad A Taqi, Tom Wolfe, Ajeet Sodhi; University of Kansas Medical Center, Kansas City, KS, Michael G Abraham; Texas Stroke Institute, Plano, TX, Vallabh Janardhan; University of Texas Health Science Center, Houston, TX, Hashem Shaltoni; UT Southwestern Medical Center, Dallas, TX, Roberta Novakovic, G Lee Pride Jr, Kim L Rickert, Babu G Welch, Jonathan A White; Massachusetts General Hospital, Boston, MA, Albert J Yoo, Thabele M Leslie-Mazwi, Joshua A Hirsch; University of Louisville Medical School, Louisville, KY, Alex Abou-Chebl; University of Texas, Houston, TX, Peng Roc Chen, Aditya Sanzgiri; Methodist Neurological Institute, Houston, TX, Gavin Britz; Duke University Medical Center, Durham, NC, Abhishek Agrawal; St Louis University, St Louis, MO, Ritesh Kaushal; University of Missouri, Columbia, MO, Ashish Nanda.
Collaborators Brian-Fred Fitzsimmons, John R Lynch, Marc A Lazzaro, Eugene Lin, Edgar Samaniego, Jennifer Domico, Jeri Sieren, Heena Olalde, Alexander M Norbash, Hesham Masoud, Judith Clark, Tom Wolfe, Ajeet Sodhi, Lee Pride Jr, Kim L Rickert, Babu G Welch, Jonathan A White, Thabele M Leslie-Mazwi, Joshua A Hirsch, Aditya Sanzgiri, and Abhishek Agrawal.
Contributors All authors participated in the design, conception, data gathering, writing, meaningful editing, suggestions, and feedback on the final manuscript.
Competing interests None.
Ethics approval Ethics approval was provided by the Medical College of Wisconsin institutional review board and the ethics committee at each participating institution.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement There are no additional unpublished data from this particular study comparing the post marketing experience of the Solitaire device with the industry sponsored prospective study. Additional questions are being addressed by other sub-papers such as: (1) The use of general anesthesia within NASA registry; (2) The use of balloon guide catheter within NASA; (3) The outcome in patients older than 80 years of age in NASA; (4) The time and recanalization as other predictors of outcome in NASA. These sub-papers are circulating among the primary NASA contributors and will be submitted to JNIS when ready.