Marc I Chimowitz

Medical University of South Carolina, Charleston, South Carolina, United States

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Publications (104)775.53 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) medical group had a much lower primary end point rate than predicted from the preceding Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. This result has been attributed to the aggressive medical therapy used in SAMMPRIS, but an alternative hypothesis is that SAMMPRIS patients were at lower risk. We undertook analyses to evaluate these competing hypotheses. Using proportional hazards regression, we compared the SAMMPRIS primary end point between SAMMPRIS medical patients and WASID patients meeting the same qualifying criteria adjusted for confounding baseline characteristics. The unadjusted comparison of the SAMMPRIS primary end point showed a significantly higher risk for WASID patients (P=0.009, logrank test) with 12 month Kaplan-Meier estimates of 21.9% in WASID and 12.6% in SAMMPRIS and hazard ratio 1.9 (95% confidence interval =1.2-3.0). The analyses identified the following confounding factors that varied between the studies and that conferred a higher risk: lack of statin use at enrollment (hazard ratio =1.8, 95% confidence interval =1.1-2.9, P=0.027) that was more prevalent among WASID patients (39% versus 14%, P<0.0001) and prior infarcts in the territory of the symptomatic vessel (hazard ratio =1.8, 95% confidence interval =1.1-2.9, P=0.023) that was more prevalent among SAMMPRIS patients (34% versus 22%, P=0.015).The hazard ratio for WASID versus SAMMPRIS adjusted for these 2 characteristics was 1.9 (95% confidence interval =1.1-3.2). After adjustment for confounding baseline characteristics, WASID patients had an almost 2-fold higher risk of the SAMMPRIS primary end point, which supports the hypothesis that the lower rate of the primary end point in the medical arm of SAMMPRIS compared with WASID patients was as a result of the aggressive medical management used in SAMMPRIS. URL: Unique identifier: NCT00576693. © 2015 American Heart Association, Inc.
    Stroke 08/2015; 46(9). DOI:10.1161/STROKEAHA.115.009656 · 5.72 Impact Factor
  • Tanya N Turan · Marc I Chimowitz
    The Lancet Neurology 04/2015; 14(6). DOI:10.1016/S1474-4422(15)00049-6 · 21.90 Impact Factor
  • Marc I Chimowitz · Colin P Derdeyn
    JAMA The Journal of the American Medical Association 03/2015; 313(12):1219-20. DOI:10.1001/jama.2015.1276 · 35.29 Impact Factor
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    ABSTRACT: Stenting has been used as a rescue therapy in patients with intracranial arterial stenosis and a transient ischemic attack or stroke when on antithrombotic therapy (AT). We determined whether the stenting versus aggressive medical therapy for intracranial arterial stenosis (SAMMPRIS) trial supported this approach by comparing the treatments within subgroups of patients whose qualifying event (QE) occurred on versus off of AT. The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared between (1) percutaneous transluminal angioplasty and stenting plus aggressive medical therapy (PTAS) versus aggressive medical management therapy alone (AMM) for patients whose QE occurred on versus off AT and between (2) patients whose QE occurred on versus off AT separately for the treatment groups. Among the 284/451 (63%) patients who had their QE on AT, the 2-year primary end point rates were 15.6% for those randomized to AMM (n=140) and 21.6% for PTAS (n=144; P=0.043, log-rank test). In the 167 patients not on AT, the 2-year primary end point rates were 11.6% for AMM (n=87) and 18.8% for PTAS (n=80; P=0.31, log-rank test). Within both treatment groups, there was no difference in the time to the primary end point between patients who were on or off AT (AMM, P=0.96; PTAS, P=0.52; log-rank test). SAMMPRIS results indicate that the benefit of AMM over PTAS is similar in patients on versus off AT at the QE and that failure of AT is not a predictor of increased risk of a primary end point. Unique identifier: NCT00576693. © 2015 American Heart Association, Inc.
    Stroke 01/2015; 46(3). DOI:10.1161/STROKEAHA.114.007752 · 5.72 Impact Factor
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    ABSTRACT: Background: There are limited data on the specific mechanisms of stroke in patients with intracranial atherosclerotic stenosis (ICAS). We undertook this study to describe infarct patterns and likely mechanisms of stroke in a large cohort of patients with ICAS, and to evaluate the relationship of these infarct patterns to angiographic features (collaterals, stenosis location and stenosis severity). Methods: We evaluated infarct patterns in the territory of a stenotic intracranial artery on neuroimaging performed at baseline and during follow-up if a recurrent stroke occurred in patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. We defined the likely mechanism of stroke (artery-to-artery embolism, perforator occlusion, hypoperfusion or mixed) according to the site of ICAS and based on the infarct patterns on neuroimaging. Collaterals were assessed using American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grades, and stenosis severity using the WASID trial's measurement technique. We evaluated the association of infarct patterns with angiographic features using χ(2) tests. Results: The likely mechanisms of stroke based on the infarct patterns at baseline in the 136 patients included in the study were artery-to-artery embolism (n = 69; 50.7%), perforator occlusion (n = 34; 25%), hypoperfusion (n = 12; 8.8%) and mixed (n = 21; 15.5%). Perforator-occlusive infarcts were more frequent in the posterior circulation, and mixed patterns were more prevalent in the anterior circulation (both p < 0.01). Most of the mixed patterns in the anterior circulation combined small pial or scattered multiple cortical infarcts with infarcts in border-zone regions, especially the cortical ones. Isolated border-zone infarcts were not significantly associated with a poor grading for collaterals or the severity of stenosis. Among 47 patients with a recurrent infarct during follow-up, the infarct patterns suggested an artery-to-artery embolic mechanism in 29 (61.7%). Conclusions: Artery-to-artery embolism is probably the most common mechanism of stroke in both the anterior and the posterior circulations in patients with ICAS. An extension of intracranial atherosclerosis at the site of stenosis into adjacent perforators also appears to be a common mechanism of stroke, particularly in the posterior circulation, whereas hypoperfusion as the sole mechanism is relatively uncommon. Further research is important to accurately establish the specific mechanisms of stroke in patients with ICAS, since preliminary data suggest that the underlying mechanism of stroke is an important determinant of prognosis.
    Cerebrovascular Diseases 07/2014; 37(6):417-422. DOI:10.1159/000362922 · 3.75 Impact Factor
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    ABSTRACT: Background. Significant racial and ethnic disparities in stroke incidence, severity, and morbidity have been consistently reported; however, less is known about potential differences in poststroke rehabilitation outcomes. Objective. To examine racial and ethnic differences in poststroke rehabilitation outcomes. Methods. We completed an in-depth search of Medline and several major journals dedicated to publishing research articles on stroke, rehabilitation, and racial-ethnic patterns of disease over a 10-year period (2003-2012). We identified studies that reported rehabilitation outcomes and the race or ethnicity of at least two groups. Results. 17 studies involving 429,108 stroke survivors met inclusion criteria for the review. The majority (94%) of studies examined outcomes between Blacks and Whites. Of those studies examining outcomes between Blacks and Whites, 59% showed that Blacks were generally less likely to achieve equivalent functional improvement following rehabilitation. Blacks were more likely to experience lower FIM gain or change scores (range: 1-60%) and more likely to have lower efficiency scores (range: 5-16%) than Whites. Conclusions. Black stroke survivors appear to generally achieve poorer functional outcomes than White stroke survivors. Future studies are warranted to evaluate the precise magnitude of these differences, whether they go beyond chance, and the underlying contributory mechanisms.
    Stroke Research and Treatment 06/2014; 2014:950746. DOI:10.1155/2014/950746
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    ABSTRACT: The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines.
    Stroke 05/2014; 45(7). DOI:10.1161/STR.0000000000000024 · 5.72 Impact Factor
  • Marc I Chimowitz
    Journal of Neurointerventional Surgery 03/2014; 6(4). DOI:10.1136/neurintsurg-2014-011187 · 2.77 Impact Factor
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    ABSTRACT: Background and purpose: Medical and endovascular treatment options for stroke prevention in patients with symptomatic intracranial stenosis have evolved over the past several decades, but the impact of 2 major multicenter randomized stroke prevention trials on physician practices has not been studied. We sought to determine changes in US physician treatment choices for patients with intracranial atherosclerotic stenosis (ICAS) following 2 NIH-funded clinical trials that studied medical therapies (antithrombotic agents and risk factor control) and percutaneous transluminal angioplasty and stenting (PTAS). Methods: Anonymous surveys on treatment practices in patients with ICAS were sent to physicians at 3 time points: before publication of the NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial (pre-WASID survey, 2004), 1 year after WASID publication (post-WASID survey, 2006) and 1 year after the publication of the NIH-funded Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (post-SAMMPRIS survey, 2012). Neurologists were invited to participate in the pre-WASID survey (n=525). Neurologists and neurointerventionists were invited to participate in the post-WASID (n=598) and post-SAMMPRIS (n=2,080) surveys. The 3 surveys were conducted using web-based survey tools delivered by E-mail, and a fax-based response form delivered by E-mail and conventional mail. Data were analyzed using the χ2 test. Results: Before WASID, there was equipoise between warfarin and aspirin for stroke prevention in patients with ICAS. The number of respondents who recommended antiplatelet treatment for ICAS increased across all 3 surveys for both anterior circulation (pre-WASID=44%, post-WASID=85%, post-SAMMPRIS=94%) and posterior circulation (pre-WASID=36%, post-WASID=74%, post-SAMMPRIS=83%). The antiplatelet agent most commonly recommended after WASID was aspirin, but after SAMMPRIS it was the combination of aspirin and clopidogrel. The percentage of neurologists who recommended PTAS in >25% of ICAS patients increased slightly from pre-WASID (8%) to post-WASID surveys (12%), but then decreased again after SAMMPRIS (6%). The percentage of neurointerventionists who recommended PTAS in >25% of ICAS patients decreased from post-WASID (49%) to post-SAMMPRIS surveys (17%). Conclusions: The surveyed US physicians' recommended treatments for ICAS differed over the 3 survey periods, reflecting the results of the 2 NIH-funded clinical trials of ICAS and suggesting that these clinical trials changed practice in the USA.
    Cerebrovascular Diseases 02/2014; 37(3):203-211. DOI:10.1159/000358120 · 3.75 Impact Factor
  • Marc I Chimowitz · Louis R Caplan
    02/2014; 71(4). DOI:10.1001/jamaneurol.2013.6224
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    ABSTRACT: BACKGROUND AND PURPOSEFractional flow may identify hemodynamic effects and ischemic risk beyond percent stenosis of an artery. We hypothesized that diminished TOF-MRA signal intensity distal to an intracranial stenosis predicts stroke risk. METHODSTOF-MRA was acquired prospectively in the SONIA-WASID trials. The distal/proximal signal intensity ratio (SIR) was calculated from 3 mm regions of interest, blinded to outcome. Univariate and multivariate analyses included clinical variables, SIR, and invasive angiography measures to identify predictors for risk of stroke in the territory. RESULTS189 patients with 50-99% symptomatic intracranial stenosis in SONIA-WASID had TOF-MRA available. In univariate analysis, the hazard ratio (HR) for stroke in the territory of the symptomatic artery with SIR < .9 was 5.2 (1.8, 15.3; P < .001) as compared to SIR ≥ .9. Multivariate analysis correcting for baseline systolic blood pressure, LDL, centrally measured percent stenosis, recency of symptoms, TICI and downstream collaterals, the HR for SIR < .9 was 10.9 (2.0, 58.9; P < .001). In those with <70% stenosis, a SIR < .9 maintained a significant association with recurrent stroke in the territory (P = .006), with a 2-year event rate of 17.3%. CONCLUSIONS Fractional flow assessed by TOF-MRA SIR may be a useful noninvasive tool to identify high-risk intracranial lesions. CLINICAL TRIAL REGISTRATION-URLThis trial was not registered because enrollment began prior to July 1, 2005.
    Journal of neuroimaging: official journal of the American Society of Neuroimaging 02/2014; 25(1). DOI:10.1111/jon.12101 · 1.73 Impact Factor
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    ABSTRACT: Background Early results of the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial showed that, by 30 days, 33 (14·7%) of 224 patients in the stenting group and 13 (5·8%) of 227 patients in the medical group had died or had a stroke (percentages are product limit estimates), but provided insufficient data to establish whether stenting offered any longer-term benefit. Here we report the long-term outcome of patients in this trial. Methods We randomly assigned (1:1, stratified by centre with randomly permuted block sizes) 451 patients with recent transient ischaemic attack or stroke related to 70–99% stenosis of a major intracranial artery to aggressive medical management (antiplatelet therapy, intensive management of vascular risk factors, and a lifestyle-modification programme) or aggressive medical management plus stenting with the Wingspan stent. The primary endpoint was any of the following: stroke or death within 30 days after enrolment, ischaemic stroke in the territory of the qualifying artery beyond 30 days of enrolment, or stroke or death within 30 days after a revascularisation procedure of the qualifying lesion during follow-up. Primary endpoint analysis of between-group differences with log-rank test was by intention to treat. This study is registered with, number NCT 00576693. Findings During a median follow-up of 32·4 months, 34 (15%) of 227 patients in the medical group and 52 (23%) of 224 patients in the stenting group had a primary endpoint event. The cumulative probability of the primary endpoints was smaller in the medical group versus the percutaneous transluminal angioplasty and stenting (PTAS) group (p=0·0252). Beyond 30 days, 21 (10%) of 210 patients in the medical group and 19 (10%) of 191 patients in the stenting group had a primary endpoint. The absolute differences in the primary endpoint rates between the two groups were 7·1% at year 1 (95% CI 0·2 to 13·8%; p=0·0428), 6·5% at year 2 (–0·5 to 13·5%; p=0·07) and 9·0% at year 3 (1·5 to 16·5%; p=0·0193). The occurrence of the following adverse events was higher in the PTAS group than in the medical group: any stroke (59 [26%] of 224 patients vs 42 [19%] of 227 patients; p=0·0468) and major haemorrhage (29 [13%]of 224 patients vs 10 [4%] of 227 patients; p=0·0009). Interpretation The early benefit of aggressive medical management over stenting with the Wingspan stent for high-risk patients with intracranial stenosis persists over extended follow-up. Our findings lend support to the use of aggressive medical management rather than PTAS with the Wingspan system in high-risk patients with atherosclerotic intracranial arterial stenosis. Funding National Institute of Neurological Disorders and Stroke (NINDS) and others.
    The Lancet 01/2014; 383(9914):333–341. DOI:10.1016/S0140-6736(13)62038-3 · 45.22 Impact Factor
  • Tanya N Turan · Alison Smock · Marc I Chimowitz
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    ABSTRACT: Patients with symptomatic intracranial atherosclerotic disease have a high risk of recurrent stroke, and secondary prevention in these patients remains a challenge. Aggressive medical management of vascular risk factors is safe and effective for most high risk patients, but the role of endovascular and surgical therapies still remain uncertain. Future studies may identify novel therapeutic strategies for patients with intracranial atherosclerotic disease, but aggressive risk factor control remains the mainstay of evidenced-based treatment at this time.
    Current Cardiology Reports 12/2013; 15(12):422. DOI:10.1007/s11886-013-0422-y · 1.93 Impact Factor
  • Christine A Holmstedt · Tanya N Turan · Marc I Chimowitz
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    ABSTRACT: Intracranial atherosclerosis is one of the most common causes of stroke worldwide and is associated with a high risk of recurrent stroke. New therapeutic approaches to treat this high-risk disease include dual antiplatelet treatment, intensive management of risk factors, and endovascular therapy. Early data from randomised trials indicate that aggressive medical therapy is better than stenting for prevention of recurrent stroke in high-risk patients with atherosclerotic stenosis of a major intracranial artery. Nevertheless, there are subgroups of patients who remain at high risk of stroke despite aggressive medical therapy. Further research is needed to identify these high-risk subgroups and to develop more effective treatments. Non-invasive vascular imaging methods that could be used to identify high-risk patients include fractional flow on magnetic resonance angiography (MRA), quantitative MRA, and high-resolution MRI of the atherosclerotic plaque. Alternative therapies to consider for future clinical trials include angioplasty alone, indirect surgical bypass procedures, ischaemic preconditioning, and new anticoagulants (direct thrombin or Xa inhibitors).
    The Lancet Neurology 11/2013; 12(11):1106-14. DOI:10.1016/S1474-4422(13)70195-9 · 21.90 Impact Factor
  • Colin P Derdeyn · David Fiorella · Marc I Chimowitz
    Neurosurgery 10/2013; 74(2). DOI:10.1227/NEU.0000000000000227 · 3.62 Impact Factor
  • Marc I Chimowitz
    Stroke 07/2013; 44(9). DOI:10.1161/STROKEAHA.113.001290 · 5.72 Impact Factor
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    Stroke 05/2013; 44(6, Supplement 1):S41-S44. DOI:10.1161/STROKEAHA.111.000370 · 5.72 Impact Factor
  • Journal of the South Carolina Medical Association (1975) 02/2013; 108(5):128-31.
  • Marc I Chimowitz
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    ABSTRACT: Most ischemic strokes are caused by an embolic or thrombotic occlusion of an intracranial artery. The immediate aims of acute stroke treatment are recanalization of the occluded artery and reperfusion of the ischemic brain region. Currently, intravenous thrombolysis that is administered within 4.5 hours after the onset of a stroke is the only proven treatment.(1),(2) However, recanalization rates within 24 hours after the administration of intravenous tissue plasminogen activator (t-PA) are low when the occlusion involves a large intracranial artery, with rates of 14% for internal carotid arteries and 55% for middle cerebral arteries.(3) These low rates have prompted . . .
    New England Journal of Medicine 02/2013; 368(10). DOI:10.1056/NEJMe1215730 · 55.87 Impact Factor
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    ABSTRACT: BACKGROUND:: Enrollment in the Stenting and Aggressive Medical Management for the Prevention of stroke in Intracranial Stenosis (SAMMPRIS) trial was halted owing to higher than expected 30-day stroke rates in the stenting arm. Improvement in peri-procedural stroke rates from angioplasty and stenting for intracranial atherosclerotic disease (ICAD) requires an understanding of the mechanisms of these events. OBJECTIVE:: To identify the types and mechanisms of peri-procedural stroke after angioplasty and stenting for ICAD. METHODS:: Patients that suffered a hemorrhagic or ischemic stroke or a cerebral infarct with temporary signs (CITS) within 30 days of attempted angioplasty and stenting in SAMMPRIS were identified. Study records, including case report forms, procedure notes, and imaging were reviewed. Strokes were categorized as ischemic or hemorrhagic. Ischemic strokes were categorized as perforator territory, distal embolic, or delayed stent thrombosis. Hemorrhagic strokes were categorized as subarachnoid or intraparenchymal. Causes of hemorrhage (wire perforation, vessel rupture) were recorded. RESULTS:: Three patients suffered an ischemic stroke after diagnostic angiography. Two were unrelated to the procedure. Twenty-one patients suffered an ischemic stroke (n= 19) or CITS (n=2) within 30 days of angioplasty and stenting. Most (n=15) were perforator territory and many of these occurred after angiographically successful angioplasty and stenting of the basilar artery (n = 8). Six patients suffered subarachnoid hemorrhage (three from wire perforation) and seven a delayed intraparenchymal hemorrhage. CONCLUSION:: Efforts at reducing complications from angioplasty and stenting for ICAD must focus on reducing the risks of regional perforator infarction, delayed intraparenchymal hemorrhage, and wire perforation.
    Neurosurgery 01/2013; 72(5). DOI:10.1227/NEU.0b013e318286fdc8 · 3.62 Impact Factor

Publication Stats

4k Citations
775.53 Total Impact Points


  • 2008–2015
    • Medical University of South Carolina
      • • Department of Neurosciences (College of Medicine)
      • • Division of Neuroradiology
      Charleston, South Carolina, United States
  • 2012
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 1995–2009
    • Emory University
      • Department of Neurology
      Atlanta, Georgia, United States
  • 2007
    • University of Pennsylvania
      • Department of Neurology
      Filadelfia, Pennsylvania, United States
  • 2004–2005
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 1994
    • University of Rochester
      • Department of Neurology
      Rochester, NY, United States
  • 1992–1994
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • Creighton University
      Omaha, Nebraska, United States
  • 1990
    • New England Baptist Hospital
      Boston, Massachusetts, United States
    • Cleveland Clinic
      • Department of Neuroradiology
      Cleveland, Ohio, United States
  • 1989
    • Tufts University
      • Department of Neurology
      Бостон, Georgia, United States