Design, progress and challenges of a double-blind trial of warfarin versus aspirin for symptomatic intracranial arterial stenosis

Marc I. Chimowitz, H. Howlett-Smith, A. Calcaterra, N. Lessard, B. Stern, M. Lynn, V. Hertzberg, G. Cotsonis, S. Swanson, T. Tutu-Gxashe, P. Griffin, A. Kosinski, C. Chester, W. Asbury, S. Rogers, M. Frankel, S. Levine, Seemant Chaturvedi, C. Benesch, A. Woolfenden & 79 others C. Sila, R. Zweifler, P. Lyden, H. Barnett, D. Easton, A. Fox, A. Furlan, P. Gorelick, R. Hart, H. Meldrum, D. Sherman, H. Cloft, P. Hudgins, F. Tong, L. Caplan, D. Anderson, V. Miller, L. Sperling, W. Weintraub, J. Marshall, S. Manoukian, O. Samuels, B. Lane, J. Braimah, S. Sailor-Smith, B. Asbury, D. Wiseman, J. Andersen, A. Sampson-Haggood, S. Kasner, D. Liebeskind, B. Cucchiara, J. Chalela, M. McGarvey, J. Luciano, S. Shaw, M. Corrozi, K. Rockwell, J. Zentner, S. Bean, D. Cole, I. Katzan, N. Rudd, M. Horvat, L. Bragg, K. Begany, G. Mazzoli, P. Teal, C. Johnston, D. Synnot, J. Busser, C. Jackson, J. Werner, N. Kelly, T. McClean, J. Gonzales, C. Adams, Jose G Romano, A. Forteza, A. Hidalgo, M. Concha, Sebastian Koch, A. Ferreira, R. Wityk, E. Aldrich, K. Lane, S. Rice, L. White, T. Traill, C. Hemphill, W. Smith, L. Hewlett, C. Reed, S. Fields, J. Nehira, L. Wechsler, J. Gebel, S. Goldstein, T. Jovin

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Background and Relevance: Atherosclerotic stenosis of the major intracranial arteries is an important cause of transient ischemic attack (TIA) or stroke. Of the 900,000 patients who suffer a TIA or stroke each year in the USA, intracranial stenosis is responsible for approximately 10%, i.e. 90,000 patients. There have been no prospective trials evaluating antithrombotic therapies for preventing recurrent vascular events in these patients. The main objective of this trial is to compare warfarin [International Normalized Ratio (INR) 2-3] with aspirin (1,300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients presenting with TIA or stroke caused by stenosis of a major intracranial artery. Study Design: Prospective, randomized, double-blind, multicenter trial. The sample size required will be 403 patients per group, based on stroke and vascular death rates of 33% per 3 years in the aspirin group vs. 22% per 3 years in the warfarin group, a p value of 0.05, power of 80%, a 24% rate of 'withdrawal of therapy', and a 1% rate of 'lost to follow-up'. Conduct of Trial: Patients with TIA or nondisabling stroke caused by ≥50% stenosis of a major intracranial artery documented by catheter angiography are randomized to warfarin or aspirin. Patients are contacted monthly by phone and examined every 4 months until a common termination date. Mean follow-up in the study is expected to be 3 years. Conclusion: This study will determine whether warfarin or aspirin is superior for patients with symptomatic intracranial arterial stenosis. Furthermore, it will identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high to justify a subsequent trial comparing intracranial angioplasty/stenting with best medical therapy in this subset of patients.

Original languageEnglish
Pages (from-to)106-117
Number of pages12
JournalNeuroepidemiology
Volume22
Issue number2
DOIs
StatePublished - Mar 20 2003
Externally publishedYes

Fingerprint

Warfarin
Aspirin
Pathologic Constriction
Stroke
Transient Ischemic Attack
Arteries
Blood Vessels
International Normalized Ratio
Lost to Follow-Up
Therapeutics
Angioplasty
Sample Size
Multicenter Studies
Angiography
Catheters
Prospective Studies
Mortality

Keywords

  • Aspirin
  • Cerebral angiography
  • Clinical trial
  • Intracranial atherosclerosis
  • Stroke
  • Warfarin

ASJC Scopus subject areas

  • Epidemiology
  • Clinical Neurology

Cite this

Chimowitz, M. I., Howlett-Smith, H., Calcaterra, A., Lessard, N., Stern, B., Lynn, M., ... Jovin, T. (2003). Design, progress and challenges of a double-blind trial of warfarin versus aspirin for symptomatic intracranial arterial stenosis. Neuroepidemiology, 22(2), 106-117. https://doi.org/10.1159/000068744

Design, progress and challenges of a double-blind trial of warfarin versus aspirin for symptomatic intracranial arterial stenosis. / Chimowitz, Marc I.; Howlett-Smith, H.; Calcaterra, A.; Lessard, N.; Stern, B.; Lynn, M.; Hertzberg, V.; Cotsonis, G.; Swanson, S.; Tutu-Gxashe, T.; Griffin, P.; Kosinski, A.; Chester, C.; Asbury, W.; Rogers, S.; Frankel, M.; Levine, S.; Chaturvedi, Seemant; Benesch, C.; Woolfenden, A.; Sila, C.; Zweifler, R.; Lyden, P.; Barnett, H.; Easton, D.; Fox, A.; Furlan, A.; Gorelick, P.; Hart, R.; Meldrum, H.; Sherman, D.; Cloft, H.; Hudgins, P.; Tong, F.; Caplan, L.; Anderson, D.; Miller, V.; Sperling, L.; Weintraub, W.; Marshall, J.; Manoukian, S.; Samuels, O.; Lane, B.; Braimah, J.; Sailor-Smith, S.; Asbury, B.; Wiseman, D.; Andersen, J.; Sampson-Haggood, A.; Kasner, S.; Liebeskind, D.; Cucchiara, B.; Chalela, J.; McGarvey, M.; Luciano, J.; Shaw, S.; Corrozi, M.; Rockwell, K.; Zentner, J.; Bean, S.; Cole, D.; Katzan, I.; Rudd, N.; Horvat, M.; Bragg, L.; Begany, K.; Mazzoli, G.; Teal, P.; Johnston, C.; Synnot, D.; Busser, J.; Jackson, C.; Werner, J.; Kelly, N.; McClean, T.; Gonzales, J.; Adams, C.; Romano, Jose G; Forteza, A.; Hidalgo, A.; Concha, M.; Koch, Sebastian; Ferreira, A.; Wityk, R.; Aldrich, E.; Lane, K.; Rice, S.; White, L.; Traill, T.; Hemphill, C.; Smith, W.; Hewlett, L.; Reed, C.; Fields, S.; Nehira, J.; Wechsler, L.; Gebel, J.; Goldstein, S.; Jovin, T.

In: Neuroepidemiology, Vol. 22, No. 2, 20.03.2003, p. 106-117.

Research output: Contribution to journalArticle

Chimowitz, MI, Howlett-Smith, H, Calcaterra, A, Lessard, N, Stern, B, Lynn, M, Hertzberg, V, Cotsonis, G, Swanson, S, Tutu-Gxashe, T, Griffin, P, Kosinski, A, Chester, C, Asbury, W, Rogers, S, Frankel, M, Levine, S, Chaturvedi, S, Benesch, C, Woolfenden, A, Sila, C, Zweifler, R, Lyden, P, Barnett, H, Easton, D, Fox, A, Furlan, A, Gorelick, P, Hart, R, Meldrum, H, Sherman, D, Cloft, H, Hudgins, P, Tong, F, Caplan, L, Anderson, D, Miller, V, Sperling, L, Weintraub, W, Marshall, J, Manoukian, S, Samuels, O, Lane, B, Braimah, J, Sailor-Smith, S, Asbury, B, Wiseman, D, Andersen, J, Sampson-Haggood, A, Kasner, S, Liebeskind, D, Cucchiara, B, Chalela, J, McGarvey, M, Luciano, J, Shaw, S, Corrozi, M, Rockwell, K, Zentner, J, Bean, S, Cole, D, Katzan, I, Rudd, N, Horvat, M, Bragg, L, Begany, K, Mazzoli, G, Teal, P, Johnston, C, Synnot, D, Busser, J, Jackson, C, Werner, J, Kelly, N, McClean, T, Gonzales, J, Adams, C, Romano, JG, Forteza, A, Hidalgo, A, Concha, M, Koch, S, Ferreira, A, Wityk, R, Aldrich, E, Lane, K, Rice, S, White, L, Traill, T, Hemphill, C, Smith, W, Hewlett, L, Reed, C, Fields, S, Nehira, J, Wechsler, L, Gebel, J, Goldstein, S & Jovin, T 2003, 'Design, progress and challenges of a double-blind trial of warfarin versus aspirin for symptomatic intracranial arterial stenosis', Neuroepidemiology, vol. 22, no. 2, pp. 106-117. https://doi.org/10.1159/000068744
Chimowitz, Marc I. ; Howlett-Smith, H. ; Calcaterra, A. ; Lessard, N. ; Stern, B. ; Lynn, M. ; Hertzberg, V. ; Cotsonis, G. ; Swanson, S. ; Tutu-Gxashe, T. ; Griffin, P. ; Kosinski, A. ; Chester, C. ; Asbury, W. ; Rogers, S. ; Frankel, M. ; Levine, S. ; Chaturvedi, Seemant ; Benesch, C. ; Woolfenden, A. ; Sila, C. ; Zweifler, R. ; Lyden, P. ; Barnett, H. ; Easton, D. ; Fox, A. ; Furlan, A. ; Gorelick, P. ; Hart, R. ; Meldrum, H. ; Sherman, D. ; Cloft, H. ; Hudgins, P. ; Tong, F. ; Caplan, L. ; Anderson, D. ; Miller, V. ; Sperling, L. ; Weintraub, W. ; Marshall, J. ; Manoukian, S. ; Samuels, O. ; Lane, B. ; Braimah, J. ; Sailor-Smith, S. ; Asbury, B. ; Wiseman, D. ; Andersen, J. ; Sampson-Haggood, A. ; Kasner, S. ; Liebeskind, D. ; Cucchiara, B. ; Chalela, J. ; McGarvey, M. ; Luciano, J. ; Shaw, S. ; Corrozi, M. ; Rockwell, K. ; Zentner, J. ; Bean, S. ; Cole, D. ; Katzan, I. ; Rudd, N. ; Horvat, M. ; Bragg, L. ; Begany, K. ; Mazzoli, G. ; Teal, P. ; Johnston, C. ; Synnot, D. ; Busser, J. ; Jackson, C. ; Werner, J. ; Kelly, N. ; McClean, T. ; Gonzales, J. ; Adams, C. ; Romano, Jose G ; Forteza, A. ; Hidalgo, A. ; Concha, M. ; Koch, Sebastian ; Ferreira, A. ; Wityk, R. ; Aldrich, E. ; Lane, K. ; Rice, S. ; White, L. ; Traill, T. ; Hemphill, C. ; Smith, W. ; Hewlett, L. ; Reed, C. ; Fields, S. ; Nehira, J. ; Wechsler, L. ; Gebel, J. ; Goldstein, S. ; Jovin, T. / Design, progress and challenges of a double-blind trial of warfarin versus aspirin for symptomatic intracranial arterial stenosis. In: Neuroepidemiology. 2003 ; Vol. 22, No. 2. pp. 106-117.
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abstract = "Background and Relevance: Atherosclerotic stenosis of the major intracranial arteries is an important cause of transient ischemic attack (TIA) or stroke. Of the 900,000 patients who suffer a TIA or stroke each year in the USA, intracranial stenosis is responsible for approximately 10{\%}, i.e. 90,000 patients. There have been no prospective trials evaluating antithrombotic therapies for preventing recurrent vascular events in these patients. The main objective of this trial is to compare warfarin [International Normalized Ratio (INR) 2-3] with aspirin (1,300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients presenting with TIA or stroke caused by stenosis of a major intracranial artery. Study Design: Prospective, randomized, double-blind, multicenter trial. The sample size required will be 403 patients per group, based on stroke and vascular death rates of 33{\%} per 3 years in the aspirin group vs. 22{\%} per 3 years in the warfarin group, a p value of 0.05, power of 80{\%}, a 24{\%} rate of 'withdrawal of therapy', and a 1{\%} rate of 'lost to follow-up'. Conduct of Trial: Patients with TIA or nondisabling stroke caused by ≥50{\%} stenosis of a major intracranial artery documented by catheter angiography are randomized to warfarin or aspirin. Patients are contacted monthly by phone and examined every 4 months until a common termination date. Mean follow-up in the study is expected to be 3 years. Conclusion: This study will determine whether warfarin or aspirin is superior for patients with symptomatic intracranial arterial stenosis. Furthermore, it will identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high to justify a subsequent trial comparing intracranial angioplasty/stenting with best medical therapy in this subset of patients.",
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T1 - Design, progress and challenges of a double-blind trial of warfarin versus aspirin for symptomatic intracranial arterial stenosis

AU - Chimowitz, Marc I.

AU - Howlett-Smith, H.

AU - Calcaterra, A.

AU - Lessard, N.

AU - Stern, B.

AU - Lynn, M.

AU - Hertzberg, V.

AU - Cotsonis, G.

AU - Swanson, S.

AU - Tutu-Gxashe, T.

AU - Griffin, P.

AU - Kosinski, A.

AU - Chester, C.

AU - Asbury, W.

AU - Rogers, S.

AU - Frankel, M.

AU - Levine, S.

AU - Chaturvedi, Seemant

AU - Benesch, C.

AU - Woolfenden, A.

AU - Sila, C.

AU - Zweifler, R.

AU - Lyden, P.

AU - Barnett, H.

AU - Easton, D.

AU - Fox, A.

AU - Furlan, A.

AU - Gorelick, P.

AU - Hart, R.

AU - Meldrum, H.

AU - Sherman, D.

AU - Cloft, H.

AU - Hudgins, P.

AU - Tong, F.

AU - Caplan, L.

AU - Anderson, D.

AU - Miller, V.

AU - Sperling, L.

AU - Weintraub, W.

AU - Marshall, J.

AU - Manoukian, S.

AU - Samuels, O.

AU - Lane, B.

AU - Braimah, J.

AU - Sailor-Smith, S.

AU - Asbury, B.

AU - Wiseman, D.

AU - Andersen, J.

AU - Sampson-Haggood, A.

AU - Kasner, S.

AU - Liebeskind, D.

AU - Cucchiara, B.

AU - Chalela, J.

AU - McGarvey, M.

AU - Luciano, J.

AU - Shaw, S.

AU - Corrozi, M.

AU - Rockwell, K.

AU - Zentner, J.

AU - Bean, S.

AU - Cole, D.

AU - Katzan, I.

AU - Rudd, N.

AU - Horvat, M.

AU - Bragg, L.

AU - Begany, K.

AU - Mazzoli, G.

AU - Teal, P.

AU - Johnston, C.

AU - Synnot, D.

AU - Busser, J.

AU - Jackson, C.

AU - Werner, J.

AU - Kelly, N.

AU - McClean, T.

AU - Gonzales, J.

AU - Adams, C.

AU - Romano, Jose G

AU - Forteza, A.

AU - Hidalgo, A.

AU - Concha, M.

AU - Koch, Sebastian

AU - Ferreira, A.

AU - Wityk, R.

AU - Aldrich, E.

AU - Lane, K.

AU - Rice, S.

AU - White, L.

AU - Traill, T.

AU - Hemphill, C.

AU - Smith, W.

AU - Hewlett, L.

AU - Reed, C.

AU - Fields, S.

AU - Nehira, J.

AU - Wechsler, L.

AU - Gebel, J.

AU - Goldstein, S.

AU - Jovin, T.

PY - 2003/3/20

Y1 - 2003/3/20

N2 - Background and Relevance: Atherosclerotic stenosis of the major intracranial arteries is an important cause of transient ischemic attack (TIA) or stroke. Of the 900,000 patients who suffer a TIA or stroke each year in the USA, intracranial stenosis is responsible for approximately 10%, i.e. 90,000 patients. There have been no prospective trials evaluating antithrombotic therapies for preventing recurrent vascular events in these patients. The main objective of this trial is to compare warfarin [International Normalized Ratio (INR) 2-3] with aspirin (1,300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients presenting with TIA or stroke caused by stenosis of a major intracranial artery. Study Design: Prospective, randomized, double-blind, multicenter trial. The sample size required will be 403 patients per group, based on stroke and vascular death rates of 33% per 3 years in the aspirin group vs. 22% per 3 years in the warfarin group, a p value of 0.05, power of 80%, a 24% rate of 'withdrawal of therapy', and a 1% rate of 'lost to follow-up'. Conduct of Trial: Patients with TIA or nondisabling stroke caused by ≥50% stenosis of a major intracranial artery documented by catheter angiography are randomized to warfarin or aspirin. Patients are contacted monthly by phone and examined every 4 months until a common termination date. Mean follow-up in the study is expected to be 3 years. Conclusion: This study will determine whether warfarin or aspirin is superior for patients with symptomatic intracranial arterial stenosis. Furthermore, it will identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high to justify a subsequent trial comparing intracranial angioplasty/stenting with best medical therapy in this subset of patients.

AB - Background and Relevance: Atherosclerotic stenosis of the major intracranial arteries is an important cause of transient ischemic attack (TIA) or stroke. Of the 900,000 patients who suffer a TIA or stroke each year in the USA, intracranial stenosis is responsible for approximately 10%, i.e. 90,000 patients. There have been no prospective trials evaluating antithrombotic therapies for preventing recurrent vascular events in these patients. The main objective of this trial is to compare warfarin [International Normalized Ratio (INR) 2-3] with aspirin (1,300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients presenting with TIA or stroke caused by stenosis of a major intracranial artery. Study Design: Prospective, randomized, double-blind, multicenter trial. The sample size required will be 403 patients per group, based on stroke and vascular death rates of 33% per 3 years in the aspirin group vs. 22% per 3 years in the warfarin group, a p value of 0.05, power of 80%, a 24% rate of 'withdrawal of therapy', and a 1% rate of 'lost to follow-up'. Conduct of Trial: Patients with TIA or nondisabling stroke caused by ≥50% stenosis of a major intracranial artery documented by catheter angiography are randomized to warfarin or aspirin. Patients are contacted monthly by phone and examined every 4 months until a common termination date. Mean follow-up in the study is expected to be 3 years. Conclusion: This study will determine whether warfarin or aspirin is superior for patients with symptomatic intracranial arterial stenosis. Furthermore, it will identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high to justify a subsequent trial comparing intracranial angioplasty/stenting with best medical therapy in this subset of patients.

KW - Aspirin

KW - Cerebral angiography

KW - Clinical trial

KW - Intracranial atherosclerosis

KW - Stroke

KW - Warfarin

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DO - 10.1159/000068744

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EP - 117

JO - Neuroepidemiology

JF - Neuroepidemiology

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