Endovascular Thrombectomy for Acute Ischemic Stroke in Failed Intravenous Tissue Plasminogen Activator Versus Non–Intravenous Tissue Plasminogen Activator Patients
Revascularization and Outcomes Stratified by the Site of Arterial Occlusions
Background and Purpose— Intracranial mechanical thrombectomy is a therapeutic option for acute ischemic stroke patients failing intravenous tissue plasminogen activator (IV tPA). We compared patients treated by mechanical embolus removal in cerebral ischemia (MERCI) thrombectomy after failed IV tPA with those treated with thrombectomy alone.
Methods— We pooled MERCI and Multi MERCI study patients, grouped them either as failed IV tPA or non–IV tPA, and assessed revascularization rates, procedural complications, symptomatic hemorrhage rates, clinical outcomes, and mortality. We also evaluated outcomes stratified by the occlusion site and final revascularization.
Results— Among 305 patients, 48 failed, and 257 were ineligible for IV tPA. Nonresponders to IV tPA trended toward a higher revascularization rate (73% versus 63%) and less mortality (27.7% versus 40.1%) and had similar rates of symptomatic hemorrhage and procedural complications. Favorable 90-day outcomes were similar in failed and non–IV tPA patients (38% versus 31%), with no difference according to occlusion site. Among patients failing IV tPA, good outcomes tended to occur more frequently in revascularized patients (47.1% versus 15.4%), although this relationship was attributable solely to middle cerebral artery and not internal carotid artery occlusions, with no difference in mortality. Among IV tPA–ineligible patients, revascularization correlated with good outcome (47.4% versus 4.4%) and less mortality (28.5% versus 59.6%).
Conclusions— The risks of hemorrhage and procedure-related complications after mechanical thrombectomy do not differ with respect to previous IV tPA administration. Thrombectomy after IV tPA achieves similar rates of good outcomes, a tendency toward lower mortality, and similar revascularization rates when stratified by clot location. Good outcomes correlate with successful revascularization except with internal carotid artery occlusions in tPA-nonresponders.
Revascularization rates in acute ischemic stroke patients with intravenous tissue plasminogen activator (IV tPA) treatment may be as low as 6% for internal carotid artery (ICA) terminus, 30% for middle cerebral artery (MCA) trunk, and 30% for basilar occlusions.1,2 Nonresponse to IV tPA is associated with poor clinical outcomes.3 Although the initial IV tPA trials did not assess revascularization,4–6 failed IV tPA patients have emerged as a subgroup with persistent occlusions, confirmed by noninvasive or catheter angiography.7–10 The time window defining failed IV tPA has not been established. Because revascularization after IV tPA is typically confirmed by transcranial Doppler ultrasonography within the first hour,11 this may be an appropriate window within which to consider rescue reperfusion therapies for IV tPA nonresponders.
The Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials were prospective, multicenter, endovascular mechanical thrombectomy trials for acute ischemic stroke patients treated within 8 hours of symptom onset who were either ineligible for or failed IV tPA therapy, introducing Merci Retriever thrombectomy as an option for acute ischemic stroke patients.12–15 The Multi MERCI trial also showed that significant hemorrhage from the combined use of IV tPA and thrombectomy (failed IV tPA group) was not significantly higher than with thrombectomy alone (non–IV tPA group).14,15 However, it is possible that the effect of nonresponse to IV tPA varies depending on occlusion location and final revascularization. We pooled data from these 2 trials and analyzed outcomes and revascularization rates in patients with failed IV tPA versus non–IV tPA, stratified by vessel occlusion.
Pooled data from the previously reported MERCI and Multi MERCI trials13,15 were analyzed retrospectively in this study. A family of Merci Retrievers (Concentric Medical, Inc.) was used to extract clot from intracranial vessels. The MERCI trial only enrolled patients who were ineligible for IV tPA. In Multi MERCI, patients receiving IV tPA (0.6 mg/kg or 0.9 mg/kg) within 3 hours of stroke onset were included if persistent vessel occlusion was confirmed by angiography. Intra-arterial (IA) tPA was only allowed in cases of thrombectomy failure after 6 passes or to treat distal embolus after successful proximal thrombectomy.
Patients were dichotomized into failed and non–IV tPA groups. Clinical variables, revascularization rates, symptomatic hemorrhage rates, clinical outcomes and mortality at 90 days, and clinically significant procedural complications were compared. Clot locations were confirmed by catheter angiography and were hierarchically categorized based on the most proximal occlusion location: ICA, MCA, or vertebro-basilar.
Successful revascularization was defined as achieving thrombolysis in myocardial infarction II or III flow in all treatable vessels (ICA, M1, M2, vertebral, and basilar) documented on final post-thrombectomy angiogram. CT or MRI brain imaging was performed at baseline, 24 hours, and at any time there was a decline in patient neurological status. Symptomatic intracranial hemorrhage was defined as a point increase of ≥4 in the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours with evidence of any blood on 24-hour head CT/MRI scan or any intracranial hemorrhage in which no additional NIHSS scores were available followed by patient death. Intracerebral hemorrhages were further categorized as hemorrhagic infarction type I and II, or parenchymal hematoma types I and II, as described previously.5 Procedure-related adverse events were adjudicated by an independent data safety 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 score of ≥4 points or death, groin complication requiring surgery, or blood transfusion.
Neurological status was quantified by the NIHSS and modified Rankin Scale (mRS) at 90 days. Good outcome at 90 days was defined as mRS ≤2. Additional comparisons of revascularization, procedural complications, good outcomes, and mortality were stratified by the occlusion site, and outcomes were further stratified by final revascularization.
Categorical data were analyzed by the Fisher exact and χ2 tests. Continuous data were assessed for normality by the Kolmogorov–Smirnov test; normally distributed continuous data were analyzed by Student t test, and for unevenly distributed continuous data, the Mann–Whitney U test was used. A P value <0.05 was considered statistically significant. No adjustment was made for multiplicity. Statistical analyses were performed using SAS software (version 8.2; SAS Institute Inc).
A total of 305 patients were enrolled in the 2 trials: 141 patients in MERCI and 164 patients in Multi MERCI. Forty-eight (15.7%) failed IV tPA, and 257 (84.3%) were not eligible to receive IV tPA before mechanical thrombectomy. In the failed IV tPA group, the mean age was 67.8±12.7 years, and 56.3% (27 of 48) were women. Mean baseline NIHSS score was 19.1±5.5. The mean IV tPA dose was 57±16 mg. In the non–IV tPA group, the mean age was 67.6±16.3 years, and 51.4% (132 of 257) were women. Mean baseline NIHSS score was 19.8±6.7. Baseline characteristics (Table 1) for these 2 populations were similar with the exception of a higher distribution of comorbid dyslipidemia in those failing IV tPA (46.8% versus 31.6%; P<0.05).
Patients with failed IV tPA tended to have a shorter time to intervention and shorter procedure duration (4.0 versus 4.4 hours). Table 1 shows the distribution of occlusion locations, categorized hierarchically by the most proximal occlusion. The distribution of occlusion location was not different between groups, with the MCA being the most common, then the ICA, and then the vertebro-basilar system.
The final revascularization rates were similar between groups (72.9% versus 63.0%), with comparable intergroup IA tPA use. In tPA-nonresponders, revascularization was achieved in 66.7% (12 of 18) of ICA, 74.1% (20 of 27) of MCA, and 100% (3 of 3) of vertebro-basilar occlusions (Table 2). In the non–IV tPA patients, revascularization was achieved in 61.7% (50 of 81), 61.6% (93 of 151), and 76.0% (19 of 25), respectively (Table 3). There was no intergroup difference.
Symptomatic Hemorrhage and Complications
Symptomatic hemorrhage was similar between groups (10.4% versus 8.6%). The 2.1% rate of symptomatic parenchymal hematoma II in patients with failed IV tPA was similar to the 1.9% rate in the non–IV tPA patients. Symptomatic hemorrhage rates by occlusion site were as follows for the failed and non–IV tPA groups, respectively: ICA, 11.1% for both; MCA, 11.1% versus 5.3%; and vertebro-basilar, 0% versus 20.0% (Tables 2 and 3⇑). Symptomatic hemorrhage in ICA occlusions was similar between groups. Although all parenchymal hematoma II hemorrhages occurred with MCA occlusions in the failed IV tPA group, the rates of all symptomatic hemorrhages for both MCA and vertebro-basilar occlusions were similar to the non–IV tPA group.
Hemorrhage by Revascularization Status
In tPA-nonresponders, symptomatic hemorrhage occurred equally by revascularization status (8.6% [3 of 35] versus 15.4% [2 of 13]). In the non–IV tPA group, revascularized patients had less symptomatic hemorrhage (4.3% [7 of 162] versus 15.8% [15 of 95]; P=0.002).
Procedural Adverse Events
Both groups had a similar rate of clinically significant procedural complications (4.2% versus 6.6%). In the failed IV tPA group, procedural complications only occurred with MCA occlusions, at a rate of 7.4%. In the non–IV tPA group, clinically significant complication rates by occlusion site were: ICA, 8.6%; MCA, 4.6%; and vertebro-basilar, 12.0%.
The rates of good clinical outcomes (mRS, 0 to 2) at 90 days were similar in the failed and non–IV tPA groups (38.3% versus 31.3%). Good outcomes by occlusion site in the failed and non–IV tPA groups were as follows, respectively (Tables 2 and 3⇑): ICA, 29.4% (5 of 17) versus 28.8% (23 of 80); MCA, 40.7% (11 of 27) versus 33.3% (46 of 138); and vertebro-basilar, 66.7% (2 of 3) versus 28.0% (7 of 25). The rate of good outcome at 90 days was similar between groups for each occlusion location.
Outcomes by Postprocedure Revascularization Status
In both groups, good clinical outcomes at 90 days occurred more frequently in subjects for whom revascularization was successful (Figure 1). In the failed IV tPA group, 47.1% (16 of 34) of revascularized patients had a good neurological outcome compared with 15.4% (2 of 13) of nonrevascularized patients (P=0.09), powered by MCA (55% versus 0%) but not ICA occlusions (27% versus 33%). In the non–IV tPA group, 47.4% (72 of 152) of revascularized patients had a good neurological outcome compared with 4.4% (4 of 91) of nonrevascularized patients (P<0.001). When stratified by occlusion site, a positive relationship existed between revascularization and good outcome, with the exception of ICA occlusions failing IV tPA.
Across cohorts, revascularized patients had a similar rate of good outcomes in both groups (47.1% versus 47.4%), whereas nonrevascularized patients in the failed IV tPA group trended toward better outcome than nonrevascularized patients in the non–IV tPA group (15.4% versus 4.4%; P=0.16). Figure 2 shows 90-day good outcomes stratified by revascularization status, IV tPA status, and occlusion location.
There was a trend toward less mortality at 90 days in the failed IV tPA group (27.7% [13 of 47] versus 40.1% [101 of 252]; P=0.08). Mortality rates in patients failing and not receiving IV tPA, by occlusion site, were as follows, respectively (Tables 2 and 3⇑): ICA, 35.3% (6 of 17) versus 50.6% (41 of 81); MCA, 22.2% (6 of 27) versus 33.6% (49 of 146); and vertebro-basilar, 33.3% (1 of 3) versus 44.0% (11 of 25). The rate of 90-day mortality was the same between groups for each occlusion location.
Mortality by Postprocedure Revascularization Status
Nonrevascularized patients had higher rates of mortality in both the failed IV tPA and non–IV tPA groups (Figure 1). Revascularized and nonrevascularized patients in the failed IV tPA groups had similar mortality at 90 days (23.5% versus 38.5%). In contrast, the mortality in the revascularized non–IV tPA group (28.5%) was lower than those not revascularized (59.6%; P<0.001).
Across cohorts, revascularized patients had a similar rate of mortality in both groups (23.5% versus 28.5%), although among nonrevascularized patients, there was trend toward decreased mortality in the failed IV tPA cohort (38.5% versus 59.6%; P=0.23). Mortality results, stratified by revascularization status and site of vascular occlusion, are shown in Figure 3.
The combination of IV tPA followed by mechanical thrombectomy achieves similar rates of good outcomes compared with thrombectomy alone. Previous IV tPA use does not increase symptomatic hemorrhage risk or procedure-related complications after thrombectomy. Revascularization rates are similar between the failed and non–IV tPA groups when stratified by occlusion location. Revascularized patients have better outcomes regardless of occlusion site.
Results from 2 different IV thrombolysis studies showed that the ICA, MCA, and basilar artery occlusions respond differently to thrombolytics, and revascularization was more frequent in distal occlusions.1,2 Revascularization and good outcomes may be improved by a combined multimodal approach.7–10,16–21 In a series of 69 patients (50 MCA, 18 ICA, and 1 basilar occlusion) treated by IA thrombolysis after nonresponse to IV tPA,9 the revascularization rate was 72.5%, similar to the 75% rate in another series of 16 patients with MCA and ICA occlusions.8
Two studies also demonstrated improved revascularization with mechanical clot disruption after failed IV tPA. In 32 patients with persistent MCA or ICA occlusion after IA or IV thrombolysis, aggressive mechanical clot disruption (angioplasty or stenting, catheter or wire clot maceration, and snare device) achieved successful revascularization (thrombolysis in myocardial infarction II/III) in 87.5% of MCA occlusions and 62.5% of ICA occlusions.16 In 7 patients with basilar occlusions treated by combined IV tPA and mechanical thrombectomy (snares and suction devices) or IA tPA, 87.5% of patients were revascularized.10
In our analysis, successful revascularization of ICA, MCA, and basilar artery occlusions was achieved with the Merci device in IV tPA nonresponders, with no difference in complications. Revascularization rates in our cohort of 66.7%, 74.1%, and 100% of ICA, MCA, and basilar occlusions, respectively, were comparable to those of previous combined approach cohorts.
We demonstrate no difference in the rates of symptomatic hemorrhage between patients either failing or ineligible for IV tPA who are subsequently treated with mechanical thrombectomy. The overall 10.4% rate of symptomatic hemorrhage in the combined IV tPA and thrombectomy group is comparable to the 8.2% rate from the pooled data of IV tPA trials.22 Our observed rate is also lower than the 12.2% rate observed in IA thrombolysis and 20% rate in IA plus IV thrombolysis from one multicenter study23 but slightly higher than the 6.2% and 5.8% rates from 2 other series of combined IA and IV thrombolysis.8,9
In our study, an 11.1% rate of symptomatic hemorrhage was found in patients with either ICA or MCA occlusions treated with a combined approach, whereas rates of symptomatic hemorrhage after thrombectomy alone were 11.1% in ICA, 5.3% in MCA, and 20% in basilar artery occlusions. Our rates of symptomatic hemorrhage in ICA occlusions in both groups were lower than the 18.8% rate seen in 16 patients treated with mechanical clot disruption after failed IV tPA.16
Patients in our study also experienced parenchymal hematoma II hemorrhage less frequently than described in Interventional Management of Stroke studies I and II, which occurred in 7.5% and 8.8% of patients, respectively.24,25 The decreased incidence of parenchymal hematoma II hemorrhages with the Merci device may be associated with the decreased use of thrombolytic drugs. Despite the theoretically increased risk of symptomatic hemorrhage with mechanical thrombectomy after failed IV tPA, there were numerically fewer procedure-related complications and mortality in the failed IV tPA group than the non–IV tPA group.
We found no difference in good outcomes and mortality between patients undergoing mechanical thrombectomy after failing or being ineligible for IV tPA. Similar rates of good outcomes have been reported in previous combined approach studies.7–10,16–21,25 In one study, 33 patients treated endovascularly (IA thrombolysis, Merci device, snare, or angioplasty) after IV tPA demonstrated lower mortality than 30 patients treated with IV tPA alone.19 In our study, good outcomes and mortality rates were similar in patients with MCA, ICA, and basilar artery occlusions treated with the combined approach. In patients undergoing thrombectomy alone, the rates of good clinical outcomes were similar among the different sites of occlusion, but there was a trend toward lower mortality in patients with MCA occlusions than basilar or ICA occlusions. The only group in this entire cohort with no notable relationship between good outcome and revascularization was in tPA-nonresponders with ICA occlusions. The implications of this finding are unclear at this time, although they may be a result of an uneven distribution of pre-MERCI disability or higher hemorrhage transformation rates after revascularization in this subgroup.
Previous endovascular studies have shown a strong association between successful revascularization and favorable clinical outcomes,13,15,26–28 and our analysis supports this assertion. In the non–IV tPA group, revascularized patients had a higher proportion of good outcomes and a lower rate of mortality. In addition, patients with revascularized MCA or basilar occlusions had better outcomes and less mortality than the nonrevascularized patients in both treatment groups. With ICA occlusions, good outcome was more frequent in revascularized patients in the non–IV tPA group but not in the failed IV tPA group.
This study has several limitations. Although the MERCI trial did not include failed IV tPA patients (by trial design), they contributed a greater number of non–IV tPA subjects for this analysis, facilitating a more meaningful comparison. Since the MERCI study, there has been progress in the Merci device, operator experience, and case selection, which may favor the failed IV tPA group (all from Multi MERCI). In addition, the failed IV tPA group presented earlier than the non IV tPA group, and since time from symptom onset to tPA bolus has also been shown to affect outcomes in the IV tPA trials, this may have contributed to detected differences.
In conclusion, the risk of symptomatic hemorrhage and procedural complication using the Merci Retriever after failed IV tPA is the same as using thrombectomy alone. Thrombectomy after IV tPA achieves similar rates of good outcomes, a tendency toward lower mortality, and similar revascularization rates when stratified by clot location. Good outcomes correlate with successful revascularization except with ICA occlusions in tPA-nonresponders.
MERCI Trial Investigators
Wade S. Smith, MD, PhD, University of California, San Francisco was the national principal investigator.
The data safety monitoring board included: 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.
The imaging core laboratory consisted of Paul Kim, MD, University of Southern California.
The writing committee included: 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.
The site principal investigators, coinvestigators, and study coordinators in order of enrollment are as follows. University of California at Los Angeles Medical Center (22): 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): 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. Saint Luke’s Hospital (21): 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): 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): John Pile-Spellman, MD; Sean Lavine, MD; Sundeep Mangla, MD; Philip Meyers, MD; and Leslie Schmidt, NP. The Stroke Center at Hartford Hospital (11): Isaac Silverman, MD; Stephen Ohki, MD; Gary Speigel, MD; Martha Ahlquist, LPN, CCRP; and Dawn Beland, MSN. NY Presbyterian Hospital–Cornell (6): 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): 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): Frank Huang-Hellinger, MD; and Susan Mitchell, RN. Riverside Methodist Hospital (5): 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): 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): 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): Vance Watson, MD; John DeSimone, MD; Manual Yepes, MD; and Theresa Kowal, RN. University of Maryland (2): Joanne Stallmeyer, MD; Abraham Obuchowski, MD; Greg Zoarski, MD; Marian LaMonte, MD; Marcella Wozniack, MD; and Deborah Schofield, RN. University of Pennsylvania (2): 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; Jessica Clarke, RN, BSN. Brigham and Women’s Hospital (1): 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): 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): 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): 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): Sten Solander, MD; Ana Felix, MD; Souvik Sen, MD; David Huang, MD; Nydia Melendez, MD; and Susan Wilson, MSN, FNP. Washoe Medical Center (1): Paul Katz, MD; Bradley Glenn, MD; Timothy Koci, MD; Anthony Bruno, MD; Mark Algood, MD; and Marta Heffner, RN. Baptist Memorial Clinical Research Center: John Barr, MD; Paul Broadbent, MD; Soren A. Singer, MD; Stephen D. Morris, MD; Sanat Dixit, MD; and Grace Miller. Barrow Neurological Institute: 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: Albert Alexander, MD; Joseph Acosta, MD; Jon Olson, MD; Kevin Callerame, MD; Rodney Hillis, MD; and Kimberly Hendricks, RN, MN. Emory University: Frank Tong, MD; Jacques Dion, MD; Michael Frankel, MD; Barney Stern, MD; Owen Samuels, MD; and Marc Chimowitz, MD. University of Texas, Houston: 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.
Multi MERCI Trial Investigators
Wade S. Smith, MD, PhD, University of California, San Francisco, was the international principal investigator.
The data safety monitoring board included: chair, Gene Sung, MD, MPH, University of Southern California; biostatistician, Phil Hormel, MS; and members, Tim W. Malisch, MD, Alexian Brothers Medical Center; Steven Rudolph, MD, Maimonides Medical Center; and Arun Amar, MD, Stanford University.
The imaging core laboratory consisted of Paul Kim, MD, University of Southern California. The biostatistician was Phil Hormel, MS.
The writing committee included: 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.
The site principal investigators, coinvestigators, and study coordinators in order of number of patients treated are as follows. St Luke’s Hospital (50): Naveed Akhtar, MD, 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): 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): 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): 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): 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): Don Frei, MD; Dan Huddle, MD; Richard Bellon, MD; Christopher Finale, MD; Carol Greenwald, MD; and Don Smith, MD. Florida Hospital Neuroscience Institute (8): Frank Hellinger, MD; Laura Billanovic, RN; and Susan Mitchell, RN. NY Presbyterian Hospital–Cornell (4): 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): John Pile-Spellman, MD; Sean Lavine, MD; Philip Meyers, MD; and Leslie Schmidt, NP. Georgetown University (3): 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): 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): 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: John Barr, MD; Paul Broadbent, MD; Sanat Dixit, MD; Grace Miller; and Stephen D. Morris, MD. University of Pittsburgh Medical Center: 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 Phil Hormel, MS, biostatistician, for his programming and assistance of the analysis.
Gary R. Duckwiler is a scientific advisor and stockholder in Concentric Medical, Inc. Gary Walker is an employee of Concentric Medical, Inc.
A list of the MERCI trial investigators appears in Appendix 1.
A list of the Multi MERCI trial investigators appears in Appendix 2.
- Received November 18, 2009.
- Revision received December 16, 2009.
- Accepted December 18, 2009.
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