Detailed Analysis of Periprocedural Strokes in Patients Undergoing Intracranial Stenting in Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS)
Background and Purpose—Enrollment in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was halted due to the high risk of stroke or death within 30 days of enrollment in the percutaneous transluminal angioplasty and stenting arm relative to the medical arm. This analysis focuses on the patient and procedural factors that may have been associated with periprocedural cerebrovascular events in the trial.
Methods—Bivariate and multivariate analyses were performed to evaluate whether patient and procedural variables were associated with cerebral ischemic or hemorrhagic events occurring within 30 days of enrollment (termed periprocedural) in the percutaneous transluminal angioplasty and stenting arm.
Results—Of 224 patients randomized to percutaneous transluminal angioplasty and stenting, 213 underwent angioplasty alone (n=5) or with stenting (n=208). Of these, 13 had hemorrhagic strokes (7 parenchymal, 6 subarachnoid), 19 had ischemic stroke, and 2 had cerebral infarcts with temporary signs within the periprocedural period. Ischemic events were categorized as perforator occlusions (13), embolic (4), mixed perforator and embolic (2), and delayed stent occlusion (2). Multivariate analyses showed that higher percent stenosis, lower modified Rankin score, and clopidogrel load associated with an activated clotting time above the target range were associated (P≤0.05) with hemorrhagic stroke. Nonsmoking, basilar artery stenosis, diabetes, and older age were associated (P≤0.05) with ischemic events.
Conclusions—Periprocedural strokes in SAMMPRIS had multiple causes with the most common being perforator occlusion. Although risk factors for periprocedural strokes could be identified, excluding patients with these features from undergoing percutaneous transluminal angioplasty and stenting to lower the procedural risk would limit percutaneous transluminal angioplasty and stenting to a small subset of patients. Moreover, given the small number of events, the present data should be used for hypothesis generation rather than to guide patient selection in clinical practice.
See related article, page 2806.
Enrollment in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was stopped due to the high rate of stroke and death within 30 days of enrollment in the stenting arm compared with the medical arm.1 In this article, we report the technical outcomes after percutaneous transluminal angioplasty and stenting (PTAS) in the trial, the types of periprocedural strokes that occurred, and a detailed analysis of the patient, lesion, and procedural characteristics that may have been associated with periprocedural cerebral ischemic and hemorrhagic events.
Study Design and Patient Population
SAMMPRIS is an investigator-initiated, randomized clinical trial funded by the National Institute of Neurological Disorders and Stroke that is being conducted at 50 sites in the United States.1,2 Medical treatment and follow-up of enrolled patients will continue until March 2013. Details of the study design have been published previously.1,2 Eligible patients had transient ischemic attack or nondisabling stroke within 30 days before enrollment attributed to angiographically verified 70% to 99% stenosis of a major intracranial artery.
PTAS in the trial was performed with the Gateway PTA Balloon Catheter and Wingspan Stent System (both manufactured by Boston Scientific Corporation). Details of the PTAS procedure, postprocedure care, and aggressive medical management (same in both arms of the trial) have already been published.2 Patients randomized to PTAS were required to undergo the procedure within 3 business days of randomization. Patients not on daily clopidogrel (75 mg) for 5 days before PTAS were given a 600-mg loading dose between 6 and 24 hours before PTAS. Intravenous heparin was administered during PTAS to achieve an activated clotting time (ACT) of between 250 and 300 seconds.
Follow-Up and Assessment of Outcome
Patients were evaluated at study entry, 4 days (by study coordinator), 30 days after enrollment, and continue to be seen every 4 months. If a periprocedural stroke was suspected, the patient was examined by a study neurologist and brain imaging was typically performed. All potential study end points were adjudicated centrally as described previously.1,2
Ischemic stroke was defined as a new focal neurological deficit of sudden onset lasting at least 24 hours that was not associated with a hemorrhage on brain CT or MRI. Cerebral infarct with temporary signs (CITS) was defined as a new infarct on brain imaging associated with neurological signs that lasted <24 hours. Symptomatic hemorrhagic stroke was defined as parenchymal, subarachnoid, or intraventricular hemorrhage detected by CT or MRI that was associated with new neurological signs or symptoms lasting ≥24 hours or a seizure. Hemorrhagic stroke associated with symptoms or signs (but no seizure) that lasted <24 hours was defined as an asymptomatic hemorrhagic stroke.
Subtype Classification of Events
All periprocedural (within 30 days after randomization) ischemic strokes, CITS, and hemorrhagic strokes were categorized by consensus of the 3 primary investigators (D.F., C.P.D., M.I.C.) based on an assessment of the available imaging and clinical data. Hemorrhagic strokes were classified as subarachnoid hemorrhages (SAHs) when the bleeding was predominantly subarachnoid and the presentations were evident immediately after the procedure or as reperfusion hemorrhages when the bleeding was predominantly intraparenchymal (ICH) and within the vascular distribution of the stented vessel. Ischemic strokes were categorized as perforator occlusions if the infarct(s) could be localized to the distribution supplied by perforating vessels arising within the margins of the stent or embolic if the infarct was in a territorial distribution distal to the treated lesion. When more than one mechanism contributed to the clinical findings, the stroke was described as mixed. Delayed stent occlusion was diagnosed if there was imaging or other presumptive evidence of stent occlusion.
In the analyses of risk factors for periprocedural events, we separated the ischemic events (stroke, CITS) from the hemorrhagic strokes. Although CITS and asymptomatic hemorrhagic strokes were not primary end points, we included these events because we were primarily interested in the underlying mechanism of ischemic and hemorrhagic injury after PTAS rather than the clinical outcome.
Bivariate associations between patient, lesion, and procedural factors and ischemic and hemorrhagic events were assessed using Fisher exact test (for categorical factors) and the independent groups t test or Wilcoxon rank-sum test (for continuous factors). Stepwise logistic regression analysis was done to relate the occurrence of an end point to multiple clinical factors. Factors were included as candidates for inclusion in the model if the probability value for the bivariate association with the end point was <0.2. The probability value for inclusion or removal from the model was 0.05. The Hosmer-Lemeshow goodness-of-fit test was used to assess the fit of the model. No adjustments were made for multiple comparisons. All analyses were done in SAS 9.2.
Technical Results of PTAS
Of the 224 patients randomized to PTAS, 4 patients declined the procedure after randomization. The procedure was initiated in the other 220 patients a median of 9 days after the qualifying event (range, 1–34 days). In these 220 cases, general anesthesia was performed in 217 (98.6%) and the ACT was maintained between 250 and 300 seconds throughout the procedure in 101 of 206 cases (49.0%) in which ACT was measured. The procedures were aborted in 6 cases without attempting PTAS owing to factors identified on angiography at the time of the planned procedure (interval occlusion of artery [n=3], resolution of stenosis to <50% [n=1], incidental adjacent aneurysm [n=1], or dissection rather than atherosclerosis [n=1]). In another case, attempts to cross the lesion with a wire were unsuccessful. On a per-patient basis (excluding the 6 patients that PTAS was not attempted and 2 patients in whom stenting was performed without predilation), an angioplasty balloon was successfully positioned across the lesion and inflated in 211 of 212 patients (99.5%). Stents were positioned and deployed across the lesion in 208 of 214 patients (97.2%) in whom PTAS was attempted (ie, 5 patients had angioplasty alone, one lesion could not be crossed).
Of the 213 procedures in which angioplasty alone or stenting was done, the number of balloons used for predilation were one in 187 cases (87.8%), 2 in 23 cases (10.8%), 3 in one case, and none in 2 cases. Of the 226 stents introduced into a guiding catheter, 208 (92.0%) were successfully navigated across the lesion and deployed. Poststenting balloon dilation was performed in 21 of 208 (10.1%) patients who had a stent placed. Stent success (ie, the lesion was accessed and a stent was placed across the stenosis resulting in <50% residual stenosis by local reading) was achieved in 197 of 214 patients (92.0%) in whom PTAS was attempted. Procedural success (ie, placement of the last stent used with <50% stenosis at the end of the procedure and without stroke or death within 24 hours of the procedure) was achieved in 174 of 214 patients (81.3%). The mean percent stenosis at the various stages of the PTAS procedures was 79.7% pre-PTAS, 40.2% postangioplasty, and 27.0% at the end of the procedure.
Types of Periprocedural Strokes
A total of 33 periprocedural strokes (14.7%) occurred among the 224 patients assigned to the PTAS arm. Ten were hemorrhagic and 23 ischemic. Three of the ischemic strokes occurred in patients in whom PTAS was not done because of findings on angiography at the time of the planned PTAS procedure. One occurred immediately after an angiogram that showed the stenosis had decreased to <50%. Two others occurred in patients whose previously stenotic artery had progressed to complete occlusion. Both had strokes in the territory of the occluded artery, one at 3 days and one at 4 days after angiography. Because PTAS was not performed in these patients, these events were omitted from the risk factor analysis. One stroke that was adjudicated as ischemic in the primary article1 was the result of intentional coil occlusion of an artery that had been perforated by a wire during the procedure. In this analysis, this event was counted as a hemorrhage yielding 19 ischemic strokes and 11 symptomatic hemorrhagic strokes.
The 19 periprocedural ischemic strokes were classified as predominantly perforator occlusions in 12, embolic in 3, mixed perforator and embolic in 2, and delayed stent occlusion in 2. The 2 strokes associated with stent occlusion occurred 4 and 6 days after the procedures and both were large ipsilateral hemisphere strokes. In addition to these ischemic strokes, there were 2 CITS, one perforator occlusion and one embolic.
Of the 11 symptomatic hemorrhagic strokes, 6 were parenchymal brain hemorrhages (ICH) and 5 were SAHs. Of the 6 ICHs, one was evident immediately after the procedure and 5 were noted when neurological signs developed ≥4 hours after PTAS. All ICHs were distributed within the vascular territory of the treated artery. Of the 6 ICHs, 4 were fatal, one resulted in a modified Rankin score (mRS) of 5, and one resulted in a mRS of 2 at 90 days. Of the 5 SAHs, all were recognized during or immediately after the procedure, none were fatal, and the resulting mRSs at 90 days were 0, 2, 3, 4, and 5, respectively.
In addition to the 11 symptomatic hemorrhagic strokes, one patient with transient postoperative nausea had a cerebellar ICH on CT (categorized as an asymptomatic reperfusion hemorrhage). A second patient had 2 syncopal events after angioplasty that prompted a CT demonstrating SAH. By definition, these 2 hemorrhages were considered asymptomatic and, together with the symptomatic hemorrhages, comprised 13 hemorrhagic strokes. Of the 34 events (21 ischemic events, 13 hemorrhagic strokes), 33 (97%) occurred within 6 days of PTAS and one CITS occurred 3 weeks later.
Risk Factors for Periprocedural Hemorrhagic Stroke
The data for all variables evaluated in the bivariate analyses for an association with hemorrhagic stroke (n=13) are provided in online-only Data Supplement Tables I and II. Tables 1 and 2 show those factors that were associated with a P<0.2 in the bivariate analyses. A stepwise logistic regression analysis involved 201 patients, including all 13 patients with hemorrhagic strokes (12 patients were excluded from the analysis because of missing data). Three factors were associated with hemorrhagic stroke in the multivariate analysis: higher percent stenosis, low mRS score (0 versus 1–3), and clopidogrel load associated with intraprocedural ACTs >300 seconds. Table 3 shows the adjusted results from the model with the OR for hemorrhagic stroke for these 3 significant variables. The model did not have a significant lack of fit (P=0.42).
Bivariate analyses for the reperfusion hemorrhages alone (n=7) showed that mean percent stenosis was higher in patients with hemorrhages (86.3%±5.6% versus 79.5%±6.7%, P=0.009) and that patients with a loading dose of clopidogrel associated with high ACTs were at higher risk (4 of 43 [9.3%] versus 3 of 165 [1.8%], P=0.03). All 7 reperfusion hemorrhages occurred after PTAS of lesions with both ≥80% stenosis and diameter at the site of stenosis of <0.6 mm. Bivariate analyses for the SAHs alone (n=6) showed that higher mean percent stenosis immediately pre-PTAS (86.5%±8.3% with SAH versus 79.5%±6.6% without SAH; P=0.01) was a risk factor.
Risk Factors for Periprocedural Ischemic Events
The data for all variables evaluated in the bivariate analyses for an association with ischemic stroke or CITS (n=21) are provided in online-only Data Supplement Tables I and II. Tables 4 to 5 show those factors that were associated with a P<0.2 in the bivariate analyses. Of note, patients with basilar stenosis had a 20.8% rate of ischemic events versus 6.7% for other arteries (P=0.01). Smoking status was a highly significant variable (P=0.002) with higher rates of ischemic events among never smokers (18.1%) than former smokers and current smokers (4.7%). Patients with qualifying events of transient ischemic attack (8.9%) or nonperforator stroke on baseline imaging (14.3%) had higher rates of ischemic events than patients with a perforator stroke on baseline imaging (0%; P=0.01).
A stepwise logistic regression analysis relating clinical factors to the occurrence of an ischemic event included 198 patients among whom there were 19 events (15 patients were excluded from the multivariate analysis because of missing data, 2 of whom had a stroke or CITS). The factors associated with an increased risk of an ischemic event in the multivariate analysis were never smoked, basilar stenosis, diabetes, and older age. Table 6 shows the adjusted results from the model with the OR for ischemic events for these significant variables. The model did not have a significant lack of fit (P=0.23).
Bivariate analyses for ischemic events involving perforator territories (n=15; 12 perforator strokes, 2 mixed perforator/embolism, one CITS) showed that older age (P=0.03), never smoked (P=0.01), old infarcts on baseline imaging (P=0.03), and basilar stenosis (P=0.007) were associated with an increased risk of perforator infarcts post-PTAS. Of 48 patients with basilar artery stenosis, 8 (16.7%) had a perforator infarct post-PTAS. No relationship was found between qualifying event type (transient ischemic attack versus acute perforator territory infarct versus acute nonperforator territory infarct on baseline imaging) and perforator infarct post-PTAS. Of 45 patients who had an acute infarct in a perforator territory on baseline imaging, none (0%) had a new perforator territory infarct after PTAS.
Time From Qualifying Event and Periprocedural Stroke
The time between the qualifying event and PTAS had no impact on the risk of a hemorrhagic event (P=0.26). In the 6 patients with SAH, the times from the qualifying event to PTAS were 4, 9, 11, 22, 24, and 27 days. In the 7 patients with ICH, the times from the qualifying event to PTAS were 3, 5, 6, 8, 20, 26, and 32 days. No relationship was found either between the proximity of PTAS to the qualifying event or the risk of an ischemic event (online-only Data Supplement Table II). The rates of ischemic stroke, symptomatic hemorrhagic stroke, or any death at 30 days were 15.7% in the PTAS arm and 7% in the medical arm in patients enrolled within 7 days of their qualifying event (P=0.02) and were 13.8% in the PTAS arm and 4.5% in the medical arm (P=0.14) in patients enrolled beyond 7 days of their qualifying event.
SAMMPRIS provides the only large prospective cohort of patients undergoing PTAS for symptomatic intracranial atherosclerosis by credentialed interventionists at multiple sites with all potential end points evaluated by site neurologists and central blinded adjudicators. As such, the trial provides unique data to evaluate the technical success of PTAS as well as the causes and risk factors for the cerebrovascular complications of PTAS.
Use of the Wingspan system in SAMMPRIS was associated with high rates of technical success confirming previous reports that the system is sufficiently flexible and of a low enough profile to allow for reliable intracranial navigation and deployment by experienced operators.3–5 Periprocedural strokes in SAMMPRIS had multiple causes with perforator occlusion being by far the most common cause of ischemic stroke and hemorrhagic stroke nearly evenly divided between SAH and reperfusion hemorrhage.
Periprocedural ischemic events were associated with never smoked, basilar stenosis, diabetes, and older age. Smokers had dramatically lower periprocedural ischemic events in SAMMPRIS than nonsmokers. This “smokers paradox,” which has also been observed after coronary interventions,6–10 may be related to the fact that nonsmokers in SAMMPRIS were more likely to be female, diabetic, and hypertensive, which may have increased their risk of periprocedural stroke compared with smokers. Additionally, smokers tend to be more responsive to clopidogrel than nonsmokers because smoking induces the hepatic cytochrome p450 system that is involved in the conversion of clopidogrel to its active metabolite.11–13 This “smokers paradox” may, in part, account for the lower risk of periprocedural stroke after PTAS that has been reported in regions of the world where smoking is more prevalent.14–16
Occlusion of perforators was the most common cause of ischemic events after PTAS, especially after basilar PTAS, as reported previously.3 This may be the result of atherosclerotic debris being displaced or “snowplowed” over the perforator origins during angioplasty or stent deployment. Of note, however, is that the perforator-rich middle cerebral artery was associated with the lowest rate of periprocedural ischemic stroke of all arteries stented in the trial (see online-only Data Supplement Table I). Advanced techniques such as high-resolution MRI of the arterial wall may be useful to identify plaque features that could lead to better selection of patients for intracranial PTAS.17,18 Importantly, SAMMPRIS showed no relationship between perforator stroke presentation and the risk of perforator stroke post-PTAS, that is, including patients with perforator stroke presentations in SAMMPRIS does not explain the high periprocedural stroke rate in the trial, as has been suggested previously.19
Hemorrhagic strokes were associated with higher percent stenosis, low mRS score, and clopidogrel load associated with high intraprocedural ACTs. Higher percent stenoses, especially in vessels with small diameters, are typically more difficult to cross with a microwire, conceivably with a higher risk of perforation. In addition, these higher grade stenoses may also be associated with more severe hemodynamic impairment, which could increase the risk of reperfusion hemorrhage when flow is restored. A higher risk of hemorrhagic stroke with a clopidogrel load and high ACTs is not surprising and attests to the challenge of balancing the risk of thrombosis and hemorrhage during the procedure. Meticulous attention to keeping the ACT range in target throughout the procedure is important but is difficult as illustrated by the fact that this was only achieved in approximately half the patients undergoing PTAS. The association between low mRS score and hemorrhagic stroke post-PTAS is difficult to explain and could be a Type I error.
The original Wingspan Humanitarian Device Exemption pilot study20 did not allow stenting within 7 days of a qualifying stroke presumably because of concerns about reperfusion hemorrhage; however, it has been suggested that stenting may offer the highest benefit in patients as soon as possible after a transient ischemic attack or stroke.19 We found no relationship between time from qualifying event to PTAS and the risks of periprocedural ischemic events or hemorrhagic stroke. Additionally, the benefit of medical therapy over PTAS at 30 days after enrollment was similar in patients enrolled within 7 days of their qualifying event compared with patients enrolled beyond 7 days. As such, these data do not suggest that a 2- to 3-week “waiting period” after the qualifying event would have benefitted those patients in the stenting arm of SAMMPRIS.
Although SAMMPRIS is the largest available prospective series of intracranial PTAS to date, the overall number of events is still relatively small. Correspondingly, it is possible that significant relationships between patient and procedural variables and the risk of periprocedural stroke could have been missed or underestimated (Type II error). Another consequence of the small number of events is that the factors identified in the regression modeling are sensitive to small changes in the data. Given the large number of analyses performed, it is also possible that some of the significant relationships between individual variables and procedural outcomes could be false-positives (Type I error). Also, as evidenced by the wide CIs, the estimates for the ORs are imprecise. As such, these data should be used for hypothesis generation only.
In summary, periprocedural strokes in SAMMPRIS encompassed all putative mechanisms of angioplasty and stenting complications. Although we identified some factors associated with an increased risk of periprocedural stroke, these factors are highly prevalent in the SAMMPRIS population (see online-only Data Supplement Tables I and II). Therefore, excluding patients with high-risk features from undergoing PTAS to lower the risk of periprocedural stroke would limit the procedure to a very small subset of patients with intracranial stenosis. Moreover, given the limitations of the present analysis, particularly the small number of events, the results should be viewed with caution and not used as the basis for clinical treatment without further confirmatory studies.
Sources of Funding
The SAMMPRIS trial was funded by a research grant (U01 NS058728) from the US Public Health Service National Institute of Neurological Disorders and Stroke (NINDS). In addition, the following Clinical and Translational Science Awards, funded by the National Institutes of Health, provided local support for the evaluation of patients in the trial: Medical University of South Carolina (UL1RR029882), University of Florida (UL1RR029889), University of Cincinnati (UL1RR029890), and University of California, San Francisco (UL1RR024131). Stryker Neurovascular (formerly Boston Scientific Neurovascular) provided study devices and supplemental funding for third party device distribution, site monitoring, and study auditing. This research is also supported by the Investigator-Sponsored Study Program of AstraZeneca that donates rosuvastatin (Crestor) to study patients.
Drs Fiorella, Derdeyn, Turan, Janis, and Chimowitz, Michael Lynn, MS, and Bethany Lane, RN, serve on the Executive Committee of the SAMMPRIS trial, which is funded by the National Institute of Neurological Disorders and Stroke (NINDS; grant number U01 NS058728). All receive salary support from the SAMMPRIS grant. All other authors were investigators in SAMMPRIS and were reimbursed from the SAMMPRIS grant for their effort. The following investigators report additional support: David Fiorella, MD, PhD, has received institutional research support from Siemens Medical Imaging and Microvention; consulting fees from Codman/Johnson and Johnson, NFocus, W.L. Gore and Associates, and EV3/Covidien; and royalties from Codman/Johnson and Johnson. He has received honoraria from Scientia and has ownership interest in CVSL and Vascular Simulations. Colin Derdeyn, MD, receives grant support from the NINDS (P50 55977; R01 NS051631). He is also on the Scientific Advisory Board for W.L Gore and Associates and is the Chair of the Scientific Advisory Board for Pulse Therapeutics. Michael J. Lynn, MS, receives grant support from the National Eye Institute. He is the principal investigator of the Coordinating Center for Infant Aphakia Treatment Study (EY013287) and a coinvestigator on the Core Grant for Vision Research (EY006360). Stanley L. Barnwell, MD, PhD, has been a consultant for Stryker Corporation. Brian L. Hoh, MD, has received research support from National Institutes of Health (NIH) grant number 1K08NS067058-01. Dr Hoh has served as an expert witness for several medical defense cases including 2 cases on an arteriovenous malformation embolism, one on a venous stent, and one on a subarachnoid hemorrhage. Elad I. Levy, MD, has received research support from Boston Scientific Corporation, Codman & Shurtleff Inc, and EV3/Covidien. Dr Levy has shareholder/ownership interest in Intratech Medical Ltd and Mynx/Access Closure. Dr Levy has acted as a consultant for Codman & Shurtleff Inc, TheraSyn Sensors Inc, and EV3/Covidien. He has received honoraria payment from Boston Scientific Corporation. Dr Levy has also received other financial/material support from Abbott Vascular and EV3/Covidien. Dr Levy has provided expertise in a legal review. Richard P. Klucznik, MD, has received payment for speakers' bureau appointments from EV3/Covidien and Microvention. Cameron G. McDougall, MD, has served on medical advisory boards for Covidien and W.L. Gore & Associates. G. Lee Pride, Jr, MD, has received research support for the ACES and LVIS trials. Dr Pride has received honoraria payment from the Texas Neurological Society (invited speaker) and ACOR (invited speaker). Osama O. Zaidat, MD, MS, has acted as a consultant for EV3/Covidien, Codman Neurovascular, Stryker Corporation, and Microvention. Michael F. Waters, MD, PhD, has received research support from an NIH K23 grant and an NIH Challenge Grant. Dr Waters has provided expertise in a legal review. J. Maurice Hourihane, MD, has served as an expert witness in a medical defense case. Andrei V. Alexandrov, MD, has received research support from NINDS for the Specialized Programs of Translational Research in Acute Stroke (SPORTRIAS) trial. Dr Alexandrov has received honoraria payment for CME lectures. He has ownership interest with Cerevast Therapeutics and has also been involved with their consultant/advisory board. Mark D. Johnson, MD, has received research support for the Insulin Resistance after Stroke Trial (IRIS), Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT), Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial (POINT) trials. Harry J. Cloft, MD, PhD, has received research support for the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) Carotid Stent registry. Bethany F. Lane, RN, has received consulting fees from Microvention Terumo. Tanya N. Turan, MD, is a past recipient of funding from the American Academy of Neurology (AAN) Foundation Clinical Research Training Fellowship and is the current recipient of a K23 grant from NIH/NINDS (1 K23 NS069668-01A1). She has also served as an expert witness in medical legal cases. Scott Janis, PhD, is a program director at the NINDS. Marc Chimowitz, MBChB, has received research grants from NINDS to fund the Aspirin Or Warfarin To Prevent Stroke (Dr WASID) trial (1 R01 NS36643) and to fund other research on intracranial stenosis (1 K24 NS050307 and 1 R01 NS051688). He currently serves on the stroke adjudication committee of an industry-funded osteoporosis drug trial (Merck and Co, Inc) and on the Data Safety Monitoring Board of another industry-funded patent foramen ovale closure trial (W.L Gore and Associates) and is compensated for those activities. He has also served as an expert witness in medical legal cases.
↵* See list of SAMMPRIS investigators in online-only Data Supplement.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.112.661173/-/DC1.
- Received April 17, 2012.
- Revision received June 12, 2012.
- Accepted June 13, 2012.
- © 2012 American Heart Association, Inc.
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