Clinical Outcomes in Middle Cerebral Artery Trunk Occlusions Versus Secondary Division Occlusions After Mechanical Thrombectomy
Pooled Analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI Trials
Background and Purpose— The benefit of endovascular revascularization of patients with acute ischemic stroke with middle cerebral artery (MCA) secondary division (M2) occlusions as compared with MCA trunk (M1) occlusions is not known. In this analysis, we compared revascularization status and clinical outcomes in patients with angiographically confirmed MCA M1 versus isolated M2 occlusions treated with mechanical thrombectomy using the Merci Retriever devices.
Methods— We retrospectively analyzed the pooled data of patients with MCA strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patient data were dichotomized into 2 groups: MCA M1 occlusions and isolated M2 occlusions. Baseline characteristics, revascularization rates, hemorrhage rates, complications, outcomes, and mortality were evaluated for both groups.
Results— Of 178 patients with MCA occlusion treated in the MERCI and Multi MERCI trials, 84.3% had M1 lesions and 15.7% had isolated M2 lesions. Patients with isolated M2 occlusions were revascularized at a higher rate, required a lower mean number of passes, and were associated with a trend toward shorter mean procedure time than patients with M1 occlusions. No statistically significant differences were found between M2 and M1 groups for symptomatic hemorrhage, clinically significant procedural adverse events, favorable 90-day outcome, or 90-day mortality, although in all instances, the M2 outcomes were numerically better than those in M1 subjects. In multivariate analysis, final revascularization was the strongest independent predictor of good outcome at 90 days.
Conclusions— Patients with both MCA M1 occlusions and isolated M2 occlusions can achieve a relatively high rate of revascularization and favorable clinical outcomes after mechanical thrombectomy. In fact, patients with isolated M2 occlusions had a higher rate of revascularization, required fewer passes, and had no increased complications compared with patients with M1 occlusions.
Patients with acute ischemic stroke caused by intracranial large vessel occlusion appear to respond differently to thrombolysis treatment depending on the occluded vessel site. In the vital randomized National Institute of Neurological Diseases and Stroke, European Cooperative Acute Stroke Study (ECASS), and Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke trials of intravenous (IV) tissue plasminogen activator (tPA), possibly due to the lack of accurate assessment of the clot location, neither the revascularization status nor clinical outcomes were influenced by the occluded vessel types.1–4 Middle cerebral artery (MCA) territory stroke accounts for the largest proportion of ischemic stroke population. However, in trials of IV and intra-arterial (IA) thrombolysis, few have reported the distinction of revascularization status and clinical outcomes between MCA trunk (M1) and isolated secondary division (M2) occlusions.1–8 Recent studies using transcranial Doppler ultrasonography and/or CT angiography revealed that the revascularization status of MCA M2 occlusions was superior to that of MCA M1 occlusions after IV tPA treatment.9,10 Patients with MCA M2 occlusions were twice as likely to have a favorable clinical outcome as patients with MCA M1 occlusions.9
The Prolyse in Acute Cerebral Thromboembolism (PROACT) II study included 61.7% of patients with MCA M1 occlusions, and the remainder presumably had isolated MCA M2 lesions; however, clinical outcomes stratified by M1 versus M2 occlusions have rarely, if ever, been reported.5 Recent studies of IA thrombolysis with urokinase treatment suggest that the revascularization status of MCA M1 occlusions was better than that of the isolated M2 occlusions, but the clinical outcome associated with the different clot lesions was not described.11,12
Mechanical thrombectomy with the Merci devices is a promising alternative treatment for patients with acute ischemic stroke who have either failed or are ineligible for IV tPA within 8 hours of initial symptom onset.13–17 As demonstrated by the pooled analysis of Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI Part I trials, patients with internal carotid artery (ICA) occlusions can achieve relatively high revascularization rates.17 However, the difference in outcomes between mechanical revascularization of the MCA M2 occlusion and the MCA M1 occlusion was not assessed. The purpose of this study was to evaluate whether angiographically confirmed MCA M1 versus isolated M2 occlusion influences the revascularization status and subsequent clinical outcomes among patients with acute ischemic stroke treated by mechanical thrombectomy with the Merci family of retriever devices. The safety and effectiveness of mechanical thrombectomy in all MCA occlusions were also compared between groups (M1 versus M2) by revascularization status.
Pooled data from the MERCI and Multi MERCI trials were retrospectively analyzed for identification of acute MCA strokes. The pooled data consisted of a total of 305 patients with ischemic stroke, 141 patients from MERCI and 164 patients from Multi MERCI. The protocol details of these 2 trials have been previously described.13–17 Briefly, enrolled patients were either ineligible for IV tPA or the occluded vessel failed to open after receiving IV tPA as confirmed by catheter angiography. A family of X series and L5 Merci Retriever devices (Concentric Medical, Inc, Mountain View, Calif) was used to attempt to restore the occluded intracranial vessel by retracting the clot from the vessel lumen. The first-generation devices (X4, X5, and X6 Retrievers) were available in both trials. The second-generation devices (L5 Retriever) were only used in Multi MERCI. IA fibrinolysis with tPA was allowed in cases of treatment failure with the device after 6 passes or to treat distal emboli not accessible to the device after successful proximal thrombectomy. Angioplasty and stenting of any lesion were not allowed per protocol.
Patients who had isolated MCA M1 and/or M2 occlusions confirmed by digital subtraction angiography were included in this study. The patients with ICA/MCA tandem or ICA-T occlusions were excluded from this analysis. The resulting patients were hierarchically dichotomized into 2 groups: an MCA M1 occlusion group and an isolated MCA M2 occlusion group. Successful revascularization was defined as achieving Thrombolysis In Myocardial Infarction (TIMI) II or III flow in all treatable vessels as confirmed by posttreatment digital subtraction angiogram. CT or MRI brain imaging was performed at baseline, 24 hours, and at any time there was a decline in patient neurological status. Intracerebral hemorrhages were categorized as hemorrhagic infarction Type I and II or parenchymal hematoma Types I and II according to the classifications of the ECASS trial. Symptomatic hemorrhage was defined as a ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours with evidence of any blood identified on 24-hour head CT/MRI scan or any intracranial hemorrhage in which no further NIHSS scores were available beyond baseline and the patient died. Procedure-related adverse events were adjudicated by an independent Data Safety and Monitoring Board and were defined as vascular perforation, intramural arterial dissection, or embolization of a previously uninvolved territory, symptomatic hemorrhage, and access site complications requiring surgery or transfusion. Clinically significant procedural complications were defined as a procedure complication with decline in NIHSS of ≥4 or death, groin complication requiring surgery, or blood transfusion.
Neurological status was quantified by the NIHSS and modified Rankin Scale (mRS) score at 30 days and 90 days. Patients in each occlusion group were assessed for revascularization rate, hemorrhagic transformation rate, clinically significant procedure-related complications, clinical outcome, and mortality at 90 days. Good outcome at 90 days was defined as mRS ≤2. Due to the relatively small sample size of isolated M2 occlusions, the data from M1 and M2 occlusions were pooled together and a multivariate logistic regression analysis was performed to determine the independent predictors of good outcome at 90 days. Further comparisons of clinical characteristics, complications, and outcomes were stratified by the revascularization status.
For comparisons of differences between groups, a 95% CI was constructed around the difference. If this interval did not contain zero, the difference was considered significant at the P=0.05 level. Although this is a retrospective subset analysis, sample sizes for the 2 groups allowed for at least 80% power of detecting a 28% absolute difference and at least 50% power for detecting a 20% absolute difference between groups in outcome rates. Univariable analyses were separately performed to identify independent predictors of good outcome at 90 days. All variables with Wald χ2 P<0.2 in univariable analysis as independent variables were included in the multivariable logistic regression model-building process to identify predictors for good outcome at 90 days. The model was built using forward/backward stepwise regression with variables entered at the 0.05 significance level and removed at the 0.10 significance level based on the χ2 statistic. After the main effects model was established, the hypothesis for the presence of any significant 2-way interaction terms was tested with the likelihood ratio χ2 (G2) statistic. The final model was then assessed for goodness of fit with the Hosmer and Lemeshow test. P<0.05 was considered statistically significant. Statistical analyses were performed using SAS software (Version 8.2; SAS Institute Inc).
Demographic Characteristics of Patients With MCA Stroke
One hundred seventy-eight patients with an angiographically confirmed MCA occlusion were treated in the MERCI and Multi MERCI trials. Of these, 80 were enrolled in MERCI and 98 were enrolled in Multi MERCI. The mean age was 69.0 (SD 15.7) years and 103 (57.9%) were women. The mean baseline NIHSS score was 18.8 (SD 5.8) points (range, 9 to 40). Twenty-seven (15.2%) patients in this cohort received IV tPA and failed to recanalize before mechanical embolectomy; the remaining 151 patients were ineligible for IV tPA. Mean time from stroke onset to arterial access was 4.3 (SD 1.6) hours (range, 0.7 to 10.8 hours).
Among the 178 patients, 84.3% (n=150) presented with an isolated MCA M1 occlusion or with a combined M1/M2 occlusion, and 15.7% (n=28) presented with an isolated MCA M2 occlusion. Among the 150 patients with MCA M1 occlusion, 73 were enrolled in MERCI and 77 were enrolled in Multi MERCI. Among the 28 patients with MCA M2 occlusion, 7 were enrolled in MERCI and 21 were enrolled in Multi MERCI. Baseline characteristics, including age, gender, NIHSS score, time from symptom onset to arterial access, and adjunctive tPA use, were not significantly different between patients in each group. Patients with MCA M1 occlusion were more likely to have coronary artery disease, a lower prothrombin time, and lower systolic blood pressure (Table 1). In the M1 cohort, the X6 and L5 devices were used most frequently (44.7% for each) with the X5 (34.0%) and X4 (6.7%) being less common. In the M2 cohort, the L5 device was most commonly used (53.6%) followed by the X6 (28.6%) and the X5 (25.0%). The X4 was not used in the M2 cohort. In both groups, 7% of patients were sedated at the time their baseline NIHSS was assessed. There was no significant difference in the motor score elements of the NIHSS between the cohorts, although there was a noticeably higher rate of severe or global aphasia in the M2 cohort (73.1%) as compared with the M1 cohort (52.5%).
Overall rates of revascularization (TIMI II/III flow) immediately after Merci treatment alone were 46.0% and 71.4% in the MCA M1 group and isolated M2 group, respectively (Table 2). The final revascularization rate for patients, including those who received adjunctive therapy, was higher in the isolated MCA M2 group than the MCA M1 group (82.1% versus 60.0%). In addition, compared with the MCA M1 occlusions, isolated MCA M2 occlusions were revascularized in fewer passes (2.1 versus 3.1) and trended toward quicker mean procedure times (1.6 versus 1.8 hours).
Good Outcome and Mortality
Favorable clinical outcomes at 90 days (mRS ≤2) were not significantly different between the 2 groups (Table 2), although there was a numerically higher frequency of good outcomes in the isolated MCA M2 occlusion group than the MCA M1 occlusion group (40.7% versus 33.3%). Although better outcomes might be expected with more distal occlusions in general, in this series, M2 occlusions were left-sided in 67.9% versus M1 occlusions being only 47.3% left-sided.
Mortality rates at 90 days were not significantly different between groups; however, it was numerically lower in the isolated MCA M2 occlusion group than in the MCA M1 occlusion group (25.9% versus 32.9%; Table 2).
Intracranial hemorrhage rates were not statistically different between groups (36.7% in the M1 group versus 42.9% in the M2 group). Symptomatic hemorrhage rates were not statistically different between groups (3.6% in the M2 group versus 6.7% in the M1 group). The patients with M2 occlusion had a numerically lower percentage of clinically significant procedure-related adverse events than the patients with M1 occlusion (3.6% versus 5.3%).
Multivariate Logistic Regression Analysis
Similar to prior MERCI trials analysis, age, baseline NIHSS, and revascularization status postprocedure were all predictors of good clinical outcomes at 90 days. The results are shown in Table 3. Final revascularization status was the strongest independent predictor of good outcomes with an OR of 30.91.
Comparison Between Revascularized and Nonrevascularized Patients
In all MCA occlusions, the revascularized patients had a higher rate of good 90-day outcomes, a lower rate of mortality and symptomatic hemorrhage, and had fewer passes and a shorter procedure time compared with the nonrevascularized patients (Table 4). Baseline characteristics, including age and NIHSS score, risk factors, and laboratory findings on admission were similar in patients with and without final revascularization postprocedure.
Results from this study suggest that patients presenting with MCA M1 occlusions or isolated M2 occlusions can achieve high revascularization rates and favorable clinical outcomes after mechanical thrombectomy with the Merci devices. Patients with isolated M2 occlusions achieved a higher revascularization rate and were associated with a trend of a shorter median procedure time.
Increasing evidence shows that revascularization rates and good clinical outcomes may be significantly impacted by the vessel occlusion location. In the IV and IA thrombolysis studies, MCA occlusions were more likely to respond to thrombolytic treatment than ICA and basilar artery occlusions.9,11 Compared with the previous analyses from the MERCI and Multi MERCI trials, the 60% revascularization rate in the MCA M1 group was similar to the 63% revascularization rate of ICA occlusions and lower than the 78% revascularization rate of vertebrobasilar artery occlusions treated with mechanical thrombectomy.17,18 The 82% revascularization rate in the isolated MCA M2 occlusions was significantly higher than other sites of occlusions.17,18
The 63.5% revascularization rate after mechanical thrombectomy for MCA occlusions observed in this study was higher than for patients treated with IV thrombolysis alone in other trials. In 1 study, transcranial Doppler-proven spontaneous recanalization within 6 hours of symptom onset occurred in 18% of the patients with MCA cardioembolic occlusions.19 In the PROACT II study, angiographically confirmed spontaneous recanalization at 6 to 8 hours after stroke onset occurred in approximately 18% of the placebo patients with acute MCA occlusion after receiving intravenous heparin.5 In another series of 82 patients with MCA main stem occlusions studied with MR angiography, based on TIMI flow grade, there was a higher spontaneous recanalization rate at 24 hours after symptom onset in the IV thrombolysis group compared with the no IV thrombolysis control group.20 The rates of partial and complete recanalization (TIMI II and III) were 38.5% in the IV thrombolysis group and 24% in the no IV thrombolysis group, respectively.20
Although the distinction of revascularization status between MCA M1 and isolated M2 occlusions was not reported in the published data from the IV thrombolysis trials, the superiority of revascularization in the isolated MCA M2 occlusions over the M1 occlusions in our study is consistent with 2 recent studies of IV thrombolysis.9,10 Based on transcranial Doppler criteria, complete recanalization up to 2 hours after IV tPA treatment was achieved in 44.2% (50 of 113 patients) and 30% (49 of 163 patients) in the MCA M2 and M1 occlusions, respectively.9 In another study with CT angiography and/or transcranial Doppler monitoring up to 24 hours after administration of IV tPA, patients with M1 occlusions (n=32) had 53% complete recanalization, whereas patients with M2 occlusions (n=19) had 68% complete recanalization.10 The comparison of recanalization rates between IV tPA followed by thrombectomy and thrombectomy alone was beyond our current study. IV tPA treatment before thrombectomy may soften the clot, facilitating clot penetration and retrieval with Merci devices. The potential benefit of recanalization induced by the combined therapy of IV tPA followed by mechanical thrombectomy in the different site arterial occlusions should be addressed in future studies.
Compared with the 121 treated patients in the PROACT II study, the patients in our cohort had similar rates of revascularization (63.5% in MERCI/Multi MERCI versus 66% in PROACT II), 90-day good outcomes (34.5% versus 40%) and mortality (31.8% versus 25%), and a lower rate of symptomatic hemorrhage (6.2% versus 10.0%), although the median baseline NIHSS score and mean age were higher in our cohort than in PROACT II (baseline NIHSS: 18 versus 17; age: 69 years versus 64 years).5 A comprehensive comparison of the data from MERCI/Multi MERCI data and PROACT is contained in a recent study.21 In a series of 100 patients with MCA occlusion treated with IA thrombolysis with urokinase, angiography showed MCA M1 occlusion in 57 patients, M2 occlusion in 21, and M3 or M4 occlusion in 22. A higher recanalization rate (76%), a better 90-day good outcome (68%), a lower mortality rate (10%), and a similar symptomatic hemorrhage rate (7%) were reported in all MCA occlusions in this study compared with those in our cohort.22 The good outcome may be associated with the low stroke score at admission (median baseline NIHSS, 14) and younger age (mean age, 61 years) in this study.
In the IA thrombolysis studies, revascularization was documented angiographically in patients with MCA strokes; however, the revascularization status and clinical outcomes stratified by the MCA M1 occlusions versus isolated M2 occlusions were not reported in these randomized clinical trials.5,8 In a large series of patients with stroke treated with IA thrombolysis with urokinase, revascularization rate (TIMI II and III) was reported in 77.6% of 147 patients with MCA M1 occlusions, whereas a 63.2% revascularization occurred in 57 patients with M2 occlusions.11 The lower rate of revascularization in isolated M2 occlusions compared with M1 occlusions differed from the results in our cohort. It is not clear if this difference was associated with the different endovascular regimens for IA thrombolysis and mechanical thrombectomy.
The data from this study further support the correlation between successful revascularization and the achievement of good clinical outcomes at 90 days postthrombectomy intervention. We found that successful revascularization was associated with a higher benefit–risk ratio in both M1 and isolated M2 occlusions. There was a trend of better clinical outcomes in patients with isolated M2 occlusions than in those with M1 occlusions. This beneficial effect on the isolated M2 lesions was also demonstrated by a transcranial Doppler study in a large series of patients who underwent IV tPA thrombolysis.9 The pooled data from Interventional Management of Stroke I and II trials showed that favorable clinical outcome in patients with isolated M2 occlusions was independent of the revascularization status because a percentage of patients with M2 occlusions achieved good clinical outcomes despite incomplete recanalization and reperfusion.6,7,23 It is not clear if the trend toward better clinical outcomes in patients with isolated M2 occlusions is associated with a higher revascularization rate or with a smaller ischemic area at risk. It is speculated that the relatively greater extent of collateral blood flow in M2 versus M1 occlusions is a potential factor in the likelihood of a given patient achieving a good clinical outcome. Although there was a trend for better outcomes in the M2 group versus the M1 group, this difference was probably minimized by the greater frequency of left-sided occlusions in the M2 group (67.9% versus 47.3%). Entry criteria for the study necessarily mandated high baseline NIHSS and therefore dominant hemisphere M2 occlusions were more likely to be enrolled.
Anecdotal case reports suggested that the occluded M2 branches can be reopened by mechanical therapy using microsnare or Attracter-18 devices if they failed to open with IA thrombolysis.24,25 However, these devices are not currently recommended for restoring blood flow in large intracranial arteries. Recently, another therapeutic tool to remove clots from the large intracranial arteries in patients with ischemic stroke, the Penumbra System, was cleared by the US Food and Drug Administration.26 This endovascular revascularization therapy may also benefit patients with stroke; however, its efficacy for isolated M2 strokes as well as M1 strokes is not yet clearly reported. In addition, the intracranial placement of self-expanding stents may be an alternative option for revascularization of acute MCA M1 occlusions, but its use in the isolated MCA M2 stroke may be limited.27
This study has several limitations. Data were retrospectively collected from 2 single-arm trials with a post hoc analysis. The sample size of patients with M2 occlusion enrolled into these 2 trials was smaller than that of the patients with M1 occlusion. Due to the fact that most of the patients with M2 occlusion were collected from the Multi MERCI trial, the better outcomes in the M2 occlusion group may result from an incorporation of knowledge gained from the practitioner’s increasing experiences and the newer generation of Merci Retriever devices available in Multi MERCI. Case selection may be biased. Baseline stroke severity was comparable in 2 groups, suggesting only patients with MCA M2 occlusion with severe neurological deficit were enrolled in 2 trials. The MCA M2 occlusion group may have included patients with large ischemic lesions at baseline or patients with initial MCA M1 or ever ICA/MCA tandem or ICA terminus occlusions who experienced IV tPA- or spontaneous-induced recanalization with futile reperfusion. This may explain the comparable clinical outcome at 3 months rather than simply the imbalance in the side of stroke among groups. Finally, the distribution of baseline antithrombotic use was not available from MERCI or Multi MERCI and could not be analyzed.
In conclusion, results from this retrospective analysis of pooled data of MERCI and Multi MERCI trials suggest that patients with isolated MCA M2 occlusions may benefit from a higher rate of revascularization and require fewer passes with Merci Retriever devices to recanalize when compared with patients with MCA M1 occlusions. Furthermore, based on a multivariate analysis using the pooled data from patients with MCA occlusions, it has been demonstrated that final revascularization is the strongest predictor of good outcomes at 90 days postprocedure.
Appendix 1: MERCI Trial Investigators
National Principal Investigator: Wade S. Smith, MD, PhD, University of California, San Francisco.
Data Safety Monitoring Board: Chair: Gene Sung, MD, University of Southern California; Biostatistician: Phil Hormel, MS; Members: Tim W. Malisch, MD, University of Illinois at Chicago; Steven L. Giannotta, MD, University of Southern California; Steven Rudolph, MD, Lenox Hill Hospital; and Fady T. Charbel, MD, University of Illinois at Chicago.
Imaging Core Laboratory: Paul Kim, MD, University of Southern California.
Writing Committee: Ronald Budzik, MD; Y. Pierre Gobin, MD; Thomas Grobelny, MD; Randall T. Higashida, MD; Chelsea Kidwell, MD; Helmi L. Lutsep, MD; Michael Marks, MD; Gary Nesbit, MD; Marilyn M. Rymer, MD; Jeffrey Saver, MD; Isaac E. Silverman, MD; Wade S. Smith, MD, PhD; Sidney Starkman, MD; and Gene Sung, MD.
Site Principal Investigator (PI), coinvestigators, and Study Coordinators in order of enrollment (N): University of California at Los Angeles Medical Center (22): PI: Sidney Starkman, MD; Gary Duckwiler, MD; Megan Leary, MD; Chelsea Kidwell, MD; Jeffrey Saver, MD; Fernando Vinuela, MD; Reza Jahan, MD; Y. Pierre Gobin, MD; and Judy Guzy, RN. Oregon Health Science University (22): PI: Helmi Lutsep, MD; Stanley Barnwell, MD; Wayne Clark, MD; Ted Lowenkopf, MD; Elizabeth North, MD; Joseph Quinn, MD; Robert Egan, MD; Todd Kuether, MD; John Roll, MD; George Luh, MD; Gary Nesbit, MD; and Barbara Dugan, RN. St Luke’s Hospital (21): PI: Thomas Grobelny, MD; Naveed Akhtar, MD; Steven Arkin, MD; Irene Bettinger, MD; Marilyn Rymer, MD; Charles Weinstein, MD; Michael Schwartzman, MD; Christine Boutwell, MD; and Barbara Gruenenfelder, RN. Massachusetts General Hospital (11): PI: Walter Koroshetz, MD; Johnny Pryor, MD; Neeraj Badjatia, MD; Ferdinando Buonarmo, MD; Lawrence Conrad, MD; David Greer, MD; Raul Nogueira, MD; James Rabinov, MD; Guy Rordorf, MD; Jonathan Rosand, MD; Lee Schwamm, MD; John Sims, MD; Eric Smith, MD; Brian Hoh, MD; Joshua Hirsch, MD; Cenk Ayata, MD; Leigh Hochberg, MD; and Joanie Cacciola, RN. NY Presbyterian Hospital–Columbia (11): PI: John Pile-Spellman, MD; Sean Lavine, MD; Sundeep Mangla, MD; Philip Meyers, MD; and Leslie Schmidt, NP. The Stroke Center at Hartford Hospital (11): PI: Isaac Silverman, MD; Stephen Ohki, MD; Gary Speigel, MD; Martha Ahlquist, LPN, CCRP; and Dawn Beland, MSN. NY Presbyterian Hospital–Cornell (6): PI: Alan Segal, MD; Ai-His Liu, MD; Igor Ougrets, MD; Howard Riina, MD; Y. Pierre Gobin, MD; and Kimberly Salvaggio, NP. University of California at San Francisco Medical Center (6): PI: Randall Higashida, MD; Christopher Dowd, MD; Van Halbach, MD; Vineeta Singh, MD; Nerissa Ko, MD; Jacob Elkins, MD; S. Claiborne Johnston, MD, PhD; J. Claude Hemphill, MD, MSc; David C. Bonovich, MD; Sharon Filler, RN; and Melissa Meighan, RN. Florida Hospital Neuroscience Institute (5): PI: Frank Huang-Hellinger, MD; Susan Mitchell, RN. Riverside Methodist Hospital (5): PI: Ronald Budzik, MD; Geoffrey Eubank, MD; Erik Arce, MD; Jim Fulop, MD; John Lippert, MD; Tom Davis, MD; J. Kevin McGraw, MD; Peter Pema, MD; and Paula Meyers, RN. Stanford University Medical Center (5): PI: Michael Marks, MD; Huy Do, MD; Gregory Albers, MD; Amie Hsia, MD; David Tong, MD; Christine Wijamn, MD; and Mary Marcellus, RN. Carolina Neurosurgery and Spine (4): PI: Joseph Bernard, MD; Gary DeFilipp, MD; Richard Bellon, MD; Barry McGinnis, MD; Andrea Dietrich, MD; Steve Putnam, MD; and Peggy Boltes, RN. Georgetown University (2): PI: Vance Watson, MD; John DeSimone, MD; Manual Yepes, MD; and Theresa Kowal, RN. University of Maryland (2): PI: Joanne Stallmeyer, MD; Abraham Obuchowski, MD; Greg Zoarski, MD; Marian LaMonte, MD; Marcella Wozniack, MD; and Deborah Schofield, RN. University of Pennsylvania (2): PI: David Liebeskind, MD; Scott Kasner, MD; Brett Cucchiara, MD; Steven Messe, MD; Robert Taylor, MD; Michael McGarvey, MD; Robert Hurst, MD; Linda Bagley, MD; John Weigele, MD; and Jessica Clarke, RN, BSN. Brigham and Women’s Hospital (1): PI: Walter Koroshetz, MD; Kai Frerichs, MD; Steven Feske, MD; Alexander Norbash, MD; Galen Hendersen, MD; Farzanah Sorond, MD; John Baker, MD; Peng Chen, MD; and Joanne O’Hara, RN. Latter-Day Saints Hospital (1): PI: John Jacobs, MD; Lisa Yananse, MD; Duane Blatter, MD; Albert Lee Bahr, MD; Collen Harker MD; David Pisani, MD; and Kathy Walker, RN. Louisiana State University at Shreveport (1): PI: Claudio Schonoholz, MD; Horacio D’Agostino, MD; Anil Nanda, MD; Roger Kelley, MD; and Donna Singleton, RN. State University of New York at Buffalo (1): PI: L. Nelson Hopkins, MD; Lee Guterman, MD; Elad Levy, MD; Jay Howington, MD; Mark Harrigan, MD; Ricardo Hanel, MD; and Annemarie Crumlish. University of North Carolina–Chapel Hill (1): PI: Sten Solander, MD; Ana Felix, MD; Souvik Sen, MD; David Huang, MD; Nydia Melendez, MD; and Susan Wilson, MSN, FNP. Washoe Medical Center (1): PI: Paul Katz, MD; Bradley Glenn, MD; Timothy Koci, MD; Anthony Bruno, MD; Mark Algood, MD; and Marta Heffner, RN. Baptist Memorial Clinical Research Center: PI: John Barr, MD; Paul Broadbent, MD; Soren A. Singer, MD; Stephen D. Morris, MD; Sanat Dixit, MD; and Grace Miller. Barrow Neurological Institute: PI: James Frey, MD; Cameron McDougall, MD; Felipe Albuquerque, MD; Mark Hekler, MD; David Fiorella, MD; Seth Larson, MD; Shafeeq Ladha, MD; Darin Okuda, MD; and Mary Harrigan, RN, MN. Baton Rouge General Hospital: PI: Albert Alexander, MD; Joseph Acosta, MD; Jon Olson, MD; Kevin Callerame, MD; Rodney Hillis, MD; and Kimberly Hendricks, RN, MN. Emory University: PI: Frank Tong, MD; Jacques Dion, MD; Michael Frankel, MD; Barney Stern, MD; Owen Samuels, MD; and Marc Chimowitz, MD. University of Texas, Houston: PI: Morgan Campbell, MD; John Choi, MD; Frank Yatsu, MD; Marc Malkoff, MD; James Grotta, MD; Edwin Cacayorin, MD; Christina Hall, MD; Lise Labiche, MD; Elizabeth Noser, MD; Joon Song, MD; Ken Uchino, MD; and Doralene Smith.
Appendix 2: Multi MERCI Trial Investigators
International Principal Investigator: Wade S. Smith, MD, PhD, University of California, San Francisco.
Data Safety Monitoring Board: Chair: Gene Sung, MD, MPH, University of Southern California. Biostatistician: Phil Hormel, MS. Members: Tim W. Malisch, MD, Alexian Brothers Medical Center; Steven Rudolph, MD, Maimonides Medical Center; and Arun Amar, MD, Stanford University.
Imaging Core Laboratory: Paul Kim, MD, University of Southern California.
Biostatistician: Phil Hormel, MS.
Writing Committee: Ronald Budzik, MD; Gary Duckwiler, MD; Donald Frei, MD; Y. Pierre Gobin, MD; Thomas Grobelny, MD; Randall T. Higashida; Frank Hellinger, MD; Dan Huddle, MD, MD; Chelsea Kidwell, MD; Walter Koroshetz, MD; David S. Liebeskind, MD; Helmi L. Lutsep, MD; Michael Marks, MD; Gary Nesbit, MD; Marilyn M. Rymer, MD; Jeffrey Saver, MD; Isaac E. Silverman, MD; Wade S. Smith, MD, PhD; Sidney Starkman, MD; and Gene Sung, MD, MPH.
Site Principal Investigator (PI), coinvestigators, and Study Coordinators in order of number of patients treated (N): St Luke’s Hospital (50): Co-PIs: Naveed Akhtar, MD, and Thomas Grobelny, MD; Annette Allen, RN; Steven Arkin, MD; Irene Bettinger, MD; Christine Boutwell, MD; Charlene Grau, RN; Barbara Gruenenfelder, RN; Marilyn Rymer, MD; Michael Schwartzman, MD; and Charles Weinstein, MD. Riverside Methodist Hospital (32): PI: Ronald Budzik, MD; Erik Arce, MD; Albert Berarducci, MD; Tom Davis, MD; Mark Dean, MD; Eric Dolen; Geoffrey Eubank, MD; Jim Fulop, MD; Xiamei Gao-Hickman, MD; John Lippert, MD; William Mayr, MD; J. Kevin McGraw, MD; Paula Meyers, RN; Peter Pema, MD; and Robert Wyatt, MD. Oregon Stroke Center (21): PI: Helmi Lutsep, MD; Stanley Barnwell, MD; Wayne Clark, MD; Barbara Dugan, RN; Robert Egan, MD; Todd Kuether, MD; Ted Lowenkopf, MD; Gary Nesbit, MD; Elizabeth North, MD; Bryan Peterson, MD; John Roll, MD; and Lisa Yanase, MD. The Stroke Center at Hartford Hospital (14): PI: Isaac Silverman, MD; Martha Ahlquist, LPN, CCRP; Dawn Beland, MSN; Joao Gomes, MD; Stephen Ohki, MD; and Gary Speigel, MD. University of California at Los Angeles Medical Center (12): PI: Sidney Starkman, MD; Latisha Ali; Brian Buck, MD; Dennis Chute, MD; Gary Duckwiler, MD; Judy Guzy, RN; Reza Jahan, MD; Doojin Kim, MD; David S. Liebeskind, MD; Victor Marder, MD; Bruce Ovbiagele, MD; Venkatakrishna Rajajee, MD; Lucas Restrepo, MD; Nerses Sanossian, MD; Jeffrey Saver, MD; Scott Selco, MD; Samir Shah, MD; Maria Shukman, RN; Satoshi Tateshima, MD; Amytis Towfighi, MD; Paul Vespa, MD; J. Pablo Villablanca, MD; Harry Vinters, MD; and Fernando Vinuela, MD. Swedish (Denver) Medical Center (9): Co-PIs: Don Frei, MD, and Dan Huddle, MD; Richard Bellon, MD; Christopher Finale, MD; Carol Greenwald, MD; and Don Smith, MD. Florida Hospital Neuroscience Institute (8): PI: Frank Hellinger, MD; Laura Billanovic, RN; and Susan Mitchell, RN. NY Presbyterian Hospital–Cornell (4): PI: Alan Segal, MD; Y. Pierre Gobin, MD; Jeffrey Katz, MD; Igor Ougrets, MD; Howard Riina, MD; and Kimberly Salvaggio, NP. University of Calgary, Foothills Hospital (4): PI: Michael Hill, MD; Philip Barker, MD; Andrew Demchuk, MD; Imanuel Dzialowski; Karyn Fischer, RN, MD; William Hu; Mark Hudon, MD; Will Morrish, MD; Suresh Subramanian, MD; Tim Watson, MD; and John Wong, MD. NY Presbyterian Hospital–Columbia (3): PI: John Pile-Spellman, MD; Sean Lavine, MD; Philip Meyers, MD; and Leslie Schmidt, NP. Georgetown University (3): PI: Vance Watson, MD; John DeSimone, MD; Timea Hodics, MD; Theresa Kowal, RN; Farid Parham, MD; Susan Sutten, MPH; and Manual Yepes, MD. Stanford University Medical Center (2): PI: Michael Marks, MD; Gregory Albers, MD; James Castle, MD; Huy Do, MD; Mahesh Jayerman, MD; Marten Lansberg, MD; Mary Marcellus, RN; Chitra Venkatsubmaran, MD; and Christine Wijman, MD. University of Alberta, Edmonton (2): PI: Ashfaq Shuaib, MD; Robert Ashforth, MD; Derek Emery, MD; Faraz Al-Hussain, MD; Muhammad Hussain, MD; Thomas Jeerakathil, MD; Kurshid Khan, MD; Mikael Murtaoghu, MD; Nazir Rizvi, MD; Maher Saqqur, MD; James Scozzafava, MD; Brenda Scwindt, RN; Muzaffar Siddiqui, MD; and Khalida Tariq, MD. Baptist Memorial Clinical Research Center: PI: John Barr, MD; Paul Broadbent, MD; Sanat Dixit, MD; Grace Miller; and Stephen D. Morris, MD. University of Pittsburgh Medical Center: PI: Tudor Jovin, MD; Max Hammer, MD; Michael Horowitz, MD; Vivek Reddy, MD; Tibetha Santucci, RN; Ken Uchino, MD; Nirav Vora, MD; and Lawrence Wechsler, MD.
We thank the MERCI writing committee for their assistance and review of the original abstract and Phil Hormel, MS, Biostatistician, Cindy Jahans (Concentric Medical), and Kirsten Valley (Concentric Medical) for their guidance, programming, and assistance of the analysis.
G.R.D. is a Scientific Advisor and stockholder in Concentric Medical, Inc. G.W. is an employee of Concentric Medical, Inc.
- Received November 2, 2009.
- Revision received December 11, 2009.
- Accepted January 19, 2010.
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