| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1995;92:2811-2818.)
© 1995 American Heart Association, Inc.
Articles |
From the University of Massachusetts Medical Center, Worcester (J.M.G.); Duke University Medical Center, Durham, NC (C.B.G., R.M.C.); Thoraxcenter-Erasmus University, Rotterdam, Netherlands (M.L.S.); University of Maryland School of Medicine, Baltimore (M.A.S.); University of Washington, Seattle (W.D.W.); Green Lane Hospital, Auckland, New Zealand (H.D.W.); Tel-Aviv-Sourasky Medical Center, Tel-Aviv, Israel (G.I.B.); University Hospital Gasthuisberg, Leuven, Belgium (F. Van de W.); Flinders Cardiovascular Centre, Adelaide, SA, Australia (P.E.A.); and the Cleveland (Ohio) Clinic Foundation (E.J.T.).
Correspondence to Joel M. Gore, MD, Department of Medicine, University of Massachusetts Medical School, 55 Lake Ave N, Worcester, MA 01655.
Background Stroke is the most feared complication of thrombolysis for acute myocardial infarction because of the resulting mortality and disability. We analyzed the incidence, timing, and outcomes of stroke in an international trial.
Methods and Results Patients were randomly assigned to one of four thrombolytic strategies. Neurological events were confirmed clinically and anatomically and were adjudicated by a blinded committee. Stroke survivors, categorized by residual deficit and disability, assessed their quality of life with a time trade-off technique. Multivariable regression identified patient characteristics associated with intracranial hemorrhage. Overall, 1.4% of the patients had a stroke (93% anatomic documentation). The risk ranged from 1.19% with streptokinase/subcutaneous heparin therapy to 1.64% with combination thrombolytic therapy (P=.007). Primary intracranial hemorrhage rates ranged from 0.46% with streptokinase/subcutaneous heparin to 0.88% with combination therapy (P<.001). Of all strokes, 41% were fatal, 31% were disabling, and 24% were nondisabling, with no significant treatment-related differences. Stroke subtype affected prognosis: 60% of patients with primary intracranial hemorrhage died and 25% were disabled versus 17% dead and 40% disabled with nonhemorrhagic infarctions. Patients with moderate or severe residual deficits showed significantly decreased quality of life. Advanced age, lower weight, prior cerebrovascular disease or hypertension, systolic and diastolic blood pressures, randomization to tissue plasminogen activator, and an interaction between age and hypertension were significant predictors of intracranial hemorrhage.
Conclusions Stroke remains a rare but catastrophic complication of thrombolysis. Additional studies should assess the net clinical benefit of thrombolysis in high-risk subgroups, particularly the elderly and patients with prior cerebrovascular events.
Key Words: thrombolysis stroke mortality trials
This article has been cited by other articles:
![]() |
J. S. Saczynski, F. A. Spencer, J. M. Gore, J. H. Gurwitz, J. Yarzebski, D. Lessard, and R. J. Goldberg Twenty-Year Trends in the Incidence of Stroke Complicating Acute Myocardial Infarction: Worcester Heart Attack Study Arch Intern Med, October 27, 2008; 168(19): 2104 - 2110. [Abstract] [Full Text] [PDF] |
||||
![]() |
R D Lopes, K S Pieper, J R Horton, S M Al-Khatib, L K Newby, R H Mehta, F Van de Werf, P W Armstrong, K W Mahaffey, R A Harrington, et al. Short- and long-term outcomes following atrial fibrillation in patients with acute coronary syndromes with or without ST-segment elevation Heart, July 1, 2008; 94(7): 867 - 873. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Schulman, R. J. Beyth, C. Kearon, and M. N. Levine Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 257S - 298S. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. S. Berger, A. Stebbins, C. B. Granger, E. M. Ohman, P. W. Armstrong, F. Van de Werf, H. D. White, R. J. Simes, R. A. Harrington, R. M. Califf, et al. Initial Aspirin Dose and Outcome Among ST-Elevation Myocardial Infarction Patients Treated With Fibrinolytic Therapy Circulation, January 15, 2008; 117(2): 192 - 199. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. P. Alexander, L. K. Newby, P. W. Armstrong, C. P. Cannon, W. B. Gibler, M. W. Rich, F. Van de Werf, H. D. White, W. D. Weaver, M. D. Naylor, et al. Acute Coronary Care in the Elderly, Part II: ST-Segment-Elevation Myocardial Infarction: A Scientific Statement for Healthcare Professionals From the American Heart Association Council on Clinical Cardiology: In Collaboration With the Society of Geriatric Cardiology Circulation, May 15, 2007; 115(19): 2570 - 2589. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Perlroth, G. D. Sanders, and M. K. Gould Effectiveness and Cost-effectiveness of Thrombolysis in Submassive Pulmonary Embolism Arch Intern Med, January 8, 2007; 167(1): 74 - 80. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Zaitsev, K. Danielyan, J.-C. Murciano, K. Ganguly, T. Krasik, R. P. Taylor, S. Pincus, S. Jones, D. B. Cines, and V. R. Muzykantov Human complement receptor type 1-directed loading of tissue plasminogen activator on circulating erythrocytes for prophylactic fibrinolysis Blood, September 15, 2006; 108(6): 1895 - 1902. [Abstract] [Full Text] [PDF] |
||||
![]() |
A G Stanley, S Fletcher, A Tan, and D B Barnett Is warfarin a contraindication to thrombolysis in acute ST elevation myocardial infarction? Heart, August 1, 2006; 92(8): 1145 - 1146. [Full Text] [PDF] |
||||
![]() |
W. C. Winkelmayer, J. S. Benner, R. J. Glynn, S. Schneeweiss, P. S. Wang, M. A. Brookhart, R. Levin, J. D. Jackson, and J. Avorn Assessing Health State Utilities in Elderly Patients at Cardiovascular Risk Med Decis Making, May 1, 2006; 26(3): 247 - 254. [Abstract] [PDF] |
||||
![]() |
P. Trouillas and R. von Kummer Classification and Pathogenesis of Cerebral Hemorrhages After Thrombolysis in Ischemic Stroke Stroke, February 1, 2006; 37(2): 556 - 561. [Abstract] [Full Text] [PDF] |
||||
![]() |
Part 8: Stabilization of the Patient With Acute Coronary Syndromes Circulation, December 13, 2005; 112(24_suppl): IV-89 - IV-110. [Full Text] [PDF] |
||||
![]() |
B. J. Witt, R. D. Brown Jr., S. J. Jacobsen, S. A. Weston, B. P. Yawn, and V. L. Roger A Community-Based Study of Stroke Incidence after Myocardial Infarction Ann Intern Med, December 6, 2005; 143(11): 785 - 792. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. E. Szummer, S. D. Solomon, E. J. Velazquez, R. Kilaru, J. McMurray, J.-L. Rouleau, K. W. Mahaffey, A. P. Maggioni, R. M. Califf, M. A. Pfeffer, et al. Heart failure on admission and the risk of stroke following acute myocardial infarction: the VALIANT registry Eur. Heart J., October 2, 2005; 26(20): 2114 - 2119. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. H. Mehta, J. H. Alexander, F. Van de Werf, P. W. Armstrong, K. S. Pieper, J. Garg, R. M. Califf, and C. B. Granger Relationship of Incorrect Dosing of Fibrinolytic Therapy and Clinical Outcomes JAMA, April 13, 2005; 293(14): 1746 - 1750. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Ingall, W. M. O'Fallon, K. Asplund, L. R. Goldfrank, V. S. Hertzberg, T. A. Louis, and T. J. H. Christianson Findings From the Reanalysis of the NINDS Tissue Plasminogen Activator for Acute Ischemic Stroke Treatment Trial Stroke, October 1, 2004; 35(10): 2418 - 2424. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Menon, R. A. Harrington, J. S. Hochman, C. P. Cannon, S. D. Goodman, R. G. Wilcox, H. J. Schunemann, and E. M. Ohman Thrombolysis and Adjunctive Therapy in Acute Myocardial Infarction: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 549S - 575S. [Abstract] [Full Text] [PDF] |
||||
![]() |
U. Stenestrand and L. Wallentin Fibrinolytic Therapy in Patients 75 Years and Older With ST-Segment-Elevation Myocardial Infarction: One-Year Follow-up of a Large Prospective Cohort Arch Intern Med, April 28, 2003; 163(8): 965 - 971. [Abstract] [Full Text] [PDF] |
||||
![]() |
The Task Force on the Management of Acute Myocardi, F. Van de Werf, D. Ardissino, A. Betriu, D. V. Cokkinos, E. Falk, K. A.A. Fox, D. Julian, M. Lengyel, F.-J. Neumann, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation Eur. Heart J., January 1, 2003; 24(1): 28 - 66. [Full Text] [PDF] |
||||
![]() |
W. F. Baker Jr Thrombolytic Therapy Clinical and Applied Thrombosis/Hemostasis, October 1, 2002; 8(4): 291 - 314. [PDF] |
||||
![]() |
S. B. Soumerai, T. J. McLaughlin, D. Ross-Degnan, C. L. Christiansen, and J. H. Gurwitz Effectiveness of Thrombolytic Therapy for Acute Myocardial Infarction in the Elderly: Cause for Concern in the Old-Old Arch Intern Med, March 11, 2002; 162(5): 561 - 568. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Van de Werf, H.V. Barron, P.W. Armstrong, C.B. Granger, S. Berioli, G. Barbash, K. Pehrsson, F.W.A. Verheugt, J. Meyer, A. Betriu, et al. Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents. A comparison of TNK-tPA and rt-PA Eur. Heart J., December 2, 2001; 22(24): 2253 - 2261. [Abstract] [PDF] |
||||
![]() |
B. G. Angeja, M. G. Shlipak, A. S. Go, S. C. Johnston, P. D. Frederick, J. G. Canto, H. V. Barron, D. Grady, and for the National Registry of Myocardial Infarction Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1297 - 1301. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. Akkerhuis, J. W. Deckers, A. M. Lincoff, J. E. Tcheng, E. Boersma, K. Anderson, C. Balog, R. M. Califf, E. J. Topol, and M. L. Simoons Risk of Stroke Associated With Abciximab Among Patients Undergoing Percutaneous Coronary Intervention JAMA, July 4, 2001; 286(1): 78 - 82. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. N. Post, A. M. Stiggelbout, and P. P. Wakker The Utility of Health States After Stroke : A Systematic Review of the Literature Stroke, June 1, 2001; 32(6): 1425 - 1429. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Ottesen, L. Kober, S. Jorgensen, C. Torp-Pedersen, and on behalf of the TRACE Study Group Consequences of overutilization and underutilization of thrombolytic therapy in clinical practice J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1581 - 1587. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. F. Graumlich, J. Eikelboom, and S. Mehta Safety of Bolus vs Infusion Thrombolytic Therapy JAMA, April 25, 2001; 285(16): 2075 - 2075. [Full Text] [PDF] |
||||
![]() |
T. O. Tengs, M. Yu, E. Luistro, and H. B. Bosworth Health-Related Quality of Life After Stroke A Comprehensive Review Editorial Comment : Health-Related Quality Of Life After Stroke: A Comprehensive Review Stroke, April 1, 2001; 32(4): 964 - 972. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. M. Ohman, R. A. Harrington, C. P. Cannon, G. Agnelli, J. A. Cairns, and J.W. Kennedy Intravenous Thrombolysis in Acute Myocardial Infarction Chest, January 1, 2001; 119(1_suppl): 253S - 277S. [Full Text] [PDF] |
||||
![]() |
L. M. Brass, J. H. Lichtman, Y. Wang, J. H. Gurwitz, M. J. Radford, and H. M. Krumholz Intracranial Hemorrhage Associated With Thrombolytic Therapy for Elderly Patients With Acute Myocardial Infarction : Results From the Cooperative Cardiovascular Project Stroke, August 1, 2000; 31(8): 1802 - 1811. [Abstract] [Full Text] [PDF] |
||||
![]() |
Trial of Abciximab With and Without Low-Dose Reteplase for Acute Myocardial Infarction Circulation, June 20, 2000; 101(24): 2788 - 2794. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Ganz, K. M. Kuntz, G. A. Jacobson, and J. Avorn Cost-Effectiveness of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor Therapy in Older Patients with Myocardial Infarction Ann Intern Med, May 16, 2000; 132(10): 780 - 787. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. S. Rathore, A. K. Berger, K. P. Weinfurt, K. A. Schulman, W. J. Oetgen, B. J. Gersh, and A. J. Solomon Acute Myocardial Infarction Complicated by Atrial Fibrillation in the Elderly : Prevalence and Outcomes Circulation, March 7, 2000; 101(9): 969 - 974. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Tanne, M. J. Gorman, V. E. Bates, S. E. Kasner, P. Scott, P. Verro, J. R. Binder, J. M. Dayno, L. R. Schultz, and S. R. Levine Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke in Patients Aged 80 Years and Older : The tPA Stroke Survey Experience Stroke, February 1, 2000; 31(2): 370 - 375. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Jaillard, C. Cornu, A. Durieux, T. Moulin, F. Boutitie, K. R. Lees, and M. Hommel Hemorrhagic Transformation in Acute Ischemic Stroke : The MAST-E Study Stroke, July 1, 1999; 30(7): 1326 - 1332. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. W. Mahaffey, R. A. Harrington, M. L. Simoons, C. B. Granger, C. Graffagnino, M. J. Alberts, D. T. Laskowitz, J. M. Miller, M. A. Sloan, L. G. Berdan, et al. Stroke in Patients With Acute Coronary Syndromes : Incidence and Outcomes in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Circulation, May 11, 1999; 99(18): 2371 - 2377. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Mooe, B.-O. Olofsson, B. Stegmayr, and P. Eriksson Ischemic Stroke : Impact of a Recent Myocardial Infarction Stroke, May 1, 1999; 30(5): 997 - 1001. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Kasirajan, N. G. Smedira, J. F. McCarthy, F. Casselman, N. Boparai, and P. M. McCarthy Risk factors for intracranial hemorrhage in adults on extracorporeal membrane oxygenation Eur. J. Cardiothorac. Surg., April 1, 1999; 15(4): 508 - 514. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Y. Tung, C. B. Granger, M. A. Sloan, E. J. Topol, J. D. Knight, W. D. Weaver, K. W. Mahaffey, H. White, N. Clapp-Channing, M. L. Simoons, et al. Effects of Stroke on Medical Resource Use and Costs in Acute Myocardial Infarction Circulation, January 26, 1999; 99(3): 370 - 376. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Demchuk, L. B. Morgenstern, D. W. Krieger, T. Linda Chi, W. Hu, T. H. Wein, R. J. Hardy, J. C. Grotta, and A. M. Buchan Serum Glucose Level and Diabetes Predict Tissue Plasminogen Activator–Related Intracerebral Hemorrhage in Acute Ischemic Stroke Stroke, January 1, 1999; 30(1): 34 - 39. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. P. Cannon, C. M. Gibson, C. H. McCabe, A. A. J. Adgey, M. J. Schweiger, R. F. Sequeira, G. Grollier, R. P. Giugliano, M. Frey, H. S. Mueller, et al. TNK–Tissue Plasminogen Activator Compared With Front-Loaded Alteplase in Acute Myocardial Infarction : Results of the TIMI 10B Trial Circulation, December 22, 1998; 98(25): 2805 - 2814. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Sloan, C. A. Sila, K. W. Mahaffey, C. B. Granger, W. T. Longstreth Jr, P. Koudstaal, H. D. White, J. M. Gore, M. L. Simoons, W. D. Weaver, et al. Prediction of 30-Day Mortality Among Patients With Thrombolysis-Related Intracranial Hemorrhage Circulation, October 6, 1998; 98(14): 1376 - 1382. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Pfisterer, J. L. Cox, C. B. Granger, S. J. Brener, C. D. Naylor, R. M. Califf, F. van de Werf, A. L. Stebbins, K. L. Lee, E. J. Topol, et al. Atenolol use and clinical outcomes after thrombolysis for acute myocardial infarction: the GUSTO-I experience J. Am. Coll. Cardiol., September 1, 1998; 32(3): 634 - 640. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. F. Lundergan, J. S. Reiner, W. F. McCarthy, K. S. Coyne, R. M. Califf, A. M. Ross, and for the GUSTO-I Angiographic Investigators Clinical predictors of early infarct-related artery patency following thrombolytic therapy: importance of body weight, smoking history, infarct-related artery and choice of thrombolytic regimen: the GUSTO-I experience J. Am. Coll. Cardiol., September 1, 1998; 32(3): 641 - 647. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. T. F. Cheung, V. L. Serebruany, V. L. MD, and P. P. A. Gurbel Depressed Platelet Status in an Elderly Patient With Hemorrhagic Stroke After Thrombolysis for Acute Myocardial Infarction • Response Stroke, September 1, 1998; 29(9): 2002 - 2003. [Full Text] |
||||
![]() |
D. Tanne, S. Gottlieb, A. Caspi, H. Hod, A. Palant, L. Reisin, T. Rosenfeld, B. Peled, A. T. Marmor, J. Balkin, et al. Treatment and Outcome of Patients With Acute Myocardial Infarction and Prior Cerebrovascular Events in the Thrombolytic Era: The Israeli Thrombolytic National Survey Arch Intern Med, March 23, 1998; 158(6): 601 - 606. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. W. Mahaffey, C. B. Granger, M. A. Sloan, T. D. Thompson, J. M. Gore, W. D. Weaver, H. D. White, M. L. Simoons, G. I. Barbash, E. J. Topol, et al. Risk Factors for In-hospital Nonhemorrhagic Stroke in Patients With Acute Myocardial Infarction Treated With Thrombolysis : Results From GUSTO-I Circulation, March 3, 1998; 97(8): 757 - 764. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. L White Thrombolytic Therapy in Acute Myocardial Infarction Part II: 1997 Update Asian Cardiovasc Thorac Ann, March 1, 1998; 6(1): 03 - 10. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Gebel, C. A. Sila, M. A. Sloan, C. B. Granger, K. W. Mahaffey, J. Weisenberger, C. L. Green, H. D. White, J. M. Gore, W. D. Weaver, et al. Thrombolysis-Related Intracranial Hemorrhage : A Radiographic Analysis of 244 Cases From the GUSTO-1 Trial With Clinical Correlation Stroke, March 1, 1998; 29(3): 563 - 569. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. J. Topol Toward a New Frontier in Myocardial Reperfusion Therapy : Emerging Platelet Preeminence Circulation, January 20, 1998; 97(2): 211 - 218. [Full Text] [PDF] |
||||
![]() |
T. N. t-P. S. S. Group Intracerebral Hemorrhage After Intravenous t-PA Therapy for Ischemic Stroke Stroke, November 1, 1997; 28(11): 2109 - 2118. [Abstract] [Full Text] |
||||
![]() |
The Global Use of Strategies to Open Occluded Coro A Comparison of Reteplase with Alteplase for Acute Myocardial Infarction N. Engl. J. Med., October 16, 1997; 337(16): 1118 - 1123. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Zijlstra, A. W J van`t Hof, A. L. Liem, J. C A Hoorntje, H. Suryapranata, and M.-J. de Boer Transferring patients for primary angioplasty: a retrospective analysis of 104 selected high risk patients with acute myocardial infarction Heart, October 1, 1997; 78(4): 333 - 336. [Abstract] [Full Text] [PDF] |
||||
![]() |
The Global Use of Strategies to Open Occluded Coro A Clinical Trial Comparing Primary Coronary Angioplasty with Tissue Plasminogen Activator for Acute Myocardial Infarction N. Engl. J. Med., June 5, 1997; 336(23): 1621 - 1628. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. D. Berkowitz, C. B. Granger, K. S. Pieper, K. L. Lee, J. M. Gore, M. Simoons, P. W. Armstrong, E. J. Topol, and R. M. Califf Incidence and Predictors of Bleeding After Contemporary Thrombolytic Therapy for Myocardial Infarction Circulation, June 3, 1997; 95(11): 2508 - 2516. [Abstract] [Full Text] |
||||
![]() |
M. A. Sloan, T. R. Price, M. L. Terrin, S. Forman, J. M. Gore, B. R. Chaitman, M. Hodges, H. Mueller, W. J. Rogers, G. L. Knatterud, et al. Ischemic Cerebral Infarction After rt-PA and Heparin Therapy for Acute Myocardial Infarction : The TIMI-II Pilot and Randomized Clinical Trial Combined Experience Stroke, June 1, 1997; 28(6): 1107 - 1114. [Abstract] [Full Text] |
||||
![]() |
T. Mooe, P. Eriksson, and B. Stegmayr Ischemic Stroke After Acute Myocardial Infarction : A Population-Based Study Stroke, April 1, 1997; 28(4): 762 - 767. [Abstract] [Full Tex |