(Circulation. 1996;94:1826-1833.)
© 1996 American Heart Association, Inc.
Articles |
Age and Outcome With Contemporary Thrombolytic Therapy
Results From the GUSTO-I Trial
Green Lane Hospital (H.D.W.), Auckland, New Zealand; Ichilov Hospital (G.I.B.), Tel Aviv, Israel; Duke University Medical Center (R.M.C., C.B.G., K.L.L.), Durham, NC; National Health Medical Research Council Clinical Trials Centre (R.J.S.), University of Sydney, Australia; University of Washington (W.D.W.), Seattle; Baylor College of Medicine/The Methodist Hospital (N.S.K.), Houston, Tex; Flinders Medical Centre (P.E.A.), Adelaide, Australia; University of Massachusetts Medical School (J.M.G.), Worcester; Hospital Tenon (A.V.), Paris, France; George Washington University Medical Center (A.M.R.), Washington, DC; and the Cleveland Clinic Foundation (E.J.T.), Cleveland, Ohio.
Correspondence to Dr Harvey White, Director of Cardiovascular Research, Green Lane Hospital, Epsom, Auckland 1003, New Zealand.
Background Elderly patients with acute myocardial infarction have much to gain from reperfusion with thrombolytic therapy but are also at increased risk of adverse events. We examined outcomes according to age of patients receiving thrombolysis in an international trial.
Methods and Results Patients were randomized to streptokinase plus subcutaneous heparin, streptokinase plus intravenous heparin, accelerated tissue plasminogen activator (TPA) plus intravenous heparin, or streptokinase and TPA plus intravenous heparin. Clinical outcomes at 30 days (death, stroke, and nonfatal, disabling stroke) and 1-year mortality were summarized descriptively for patients aged <65 (n=24 708), 65 to 74 (n=11 201), 75 to 85 (n=4625), and >85 years (n=412) and assessed as continuous functions of age. Older patients had a higher-risk profile with regard to baseline clinical and angiographic characteristics. Mortality at 30 days increased markedly with age (3.0%, 9.5%, 19.6%, and 30.3% in the four groups, respectively), as did stroke, cardiogenic shock, bleeding, and reinfarction. Combined death or disabling stroke occurred less often with accelerated TPA in all but the oldest patients, who showed a weak trend toward a lower incidence with streptokinase plus subcutaneous heparin: odds ratio 1.13; 95% confidence interval 0.6, 2.1. Similarly, accelerated TPA treatment resulted in lower 1-year mortality in all but the oldest patients (47% TPA versus 40.3% streptokinase).
Conclusions Lower mortality and greater net clinical benefit were seen with accelerated TPA in patients aged 
85 years. Because data are limited for patients aged >85 years, the relative superiority of a given thrombolytic regimen cannot be determined. The interactions of stroke and mortality with newer thrombolytic strategies must be examined explicitly in older patients.
Key Words: thrombolysis • tissue plasminogen activator • aging • streptokinase
This article has been cited by other articles:
 |
|
 |
|
  J. D. O'Brien, J. H. Ferguson, and S. E. Howlett Effects of ischemia and reperfusion on isolated ventricular myocytes from young adult and aged Fischer 344 rat hearts Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2174 - H2183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z Motovska, P Widimsky, M Aschermann, and on behalf of The PRAGUE Study Group Investigators The impact of gender on outcomes of patients with ST elevation myocardial infarction transported for percutaneous coronary intervention: analysis of the PRAGUE-1 and 2 studies Heart, March 1, 2008; 94(3): e5 - e5. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jahangir, S. Sagar, and A. Terzic Aging and cardioprotection J Appl Physiol, December 1, 2007; 103(6): 2120 - 2128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine J. Am. Coll. Cardiol., August 14, 2007; 50(7): e1 - e157. [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]
|
|
|
|
 |
|
 S. P. Schulman and G. Gerstenblith Arginine Therapy for Acute Myocardial Infarction--Reply JAMA, May 10, 2006; 295(18): 2139 - 2140. [Full Text] [PDF]
|
|
|
|
|
|
S. P. Schulman, L. C. Becker, D. A. Kass, H. C. Champion, M. L. Terrin, S. Forman, K. V. Ernst, M. D. Kelemen, S. N. Townsend, A. Capriotti, et al. L-Arginine Therapy in Acute Myocardial Infarction: The Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) Randomized Clinical Trial JAMA, January 4, 2006; 295(1): 58 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bueno, M. Martinez-Selles, E. Perez-David, and R. Lopez-Palop Mechanisms of death in elderly patients with acute myocardial infarction exposed to fibrinolytic therapy: reply Eur. Heart J., January 2, 2006; 27(2): 246 - 247. [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]
|
|
|
|
|
|
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, C. B. Granger, K. P. Alexander, E. Bossone, H. D. White, and M. H. Sketch Jr Reperfusion strategies for acute myocardial infarction in the elderly: Benefits and risks J. Am. Coll. Cardiol., February 15, 2005; 45(4): 471 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Lakatta and S. Schulman Age-associated cardiovascular changes are the substrate for poor prognosis with myocardial infarction J. Am. Coll. Cardiol., July 7, 2004; 44(1): 35 - 37. [Full Text] [PDF]
|
|
|
|
 |
|
 C.-I Cheng, K.-H. Yeh, H.-W. Chang, T.-H. Yu, Y.-H. Chen, H.-T. Chai, and H.-K. Yip Comparison of Baseline Characteristics, Clinical Features, Angiographic Results, and Early Outcomes in Men vs Women With Acute Myocardial Infarction Undergoing Primary Coronary Intervention Chest, July 1, 2004; 126(1): 47 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-K. Yip, C.-J. Wu, H.-W. Chang, C.-P. Wang, C.-I Cheng, S. Chua, and M.-C. Chen Cardiac Rupture Complicating Acute Myocardial Infarction in the Direct Percutaneous Coronary Intervention Reperfusion Era Chest, August 1, 2003; 124(2): 565 - 571. [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]
|
|
|
|
 |
|
 R. H. Mehta, K. A. Eagle, L. P. Coombs, E. D. Peterson, F. H. Edwards, F. D. Pagani, G. M. Deeb, S. F. Bolling, and R. L. Prager Influence of age on outcomes in patients undergoing mitral valve replacement Ann. Thorac. Surg., November 1, 2002; 74(5): 1459 - 1467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Thiemann Primary angioplasty for elderly patients with myocardial infarction: Theory, practice and possibilities J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1729 - 1732. [Full Text] [PDF]
|
|
|
|
|
|
J M Estess and E J Topol Fibrinolytic treatment for elderly patients with acute myocardial infarction Heart, April 1, 2002; 87(4): 308 - 311. [Full Text] [PDF]
|
|
|
|
|
|
K. E. Gould, G. E. Taffet, L. H. Michael, R. M. Christie, D. L. Konkol, J. S. Pocius, J. P. Zachariah, D. F. Chaupin, S. L. Daniel, G. E. Sandusky Jr., et al. Heart failure and greater infarct expansion in middle-aged mice: a relevant model for postinfarction failure Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H615 - H621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Napoli, G. Aldini, J. L. Wallace, F. de Nigris, R. Maffei, P. Abete, D. Bonaduce, G. Condorelli, F. Rengo, V. Sica, et al. Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosis PNAS, January 24, 2002; (2002) 22639399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. del Mar de la Torre, J. A. San Roman, J. Bermejo, G. Pastor, J. Alonso, and F. Fernandez-Aviles Prognostic Power of Dobutamine Echocardiography After Uncomplicated Acute Myocardial Infarction in the Elderly Chest, October 1, 2001; 120(4): 1200 - 1205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Schulman, D. S. Latchman, and D. M. Yellon Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1630 - H1636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Mehta, S. S. Rathore, M. J. Radford, Y. Wang, Y. Wang, and H. M. Krumholz Acute myocardial infarction in the elderly: differences by age J. Am. Coll. Cardiol., September 1, 2001; 38(3): 736 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Braunwald, E. M. Antman, J. W. Beasley, R. M. Califf, M. D. Cheitlin, J. S. Hochman, R. H. Jones, D. Kereiakes, J. Kupersmith, T. N. Levin, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on the management of patients with unstable angina) J. Am. Coll. Cardiol., September 1, 2000; 36(3): 970 - 1062. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Califf, K. S. Pieper, K. L. Lee, F. Van de Werf, R. J. Simes, P. W. Armstrong, and E. J. Topol Prediction of 1-Year Survival After Thrombolysis for Acute Myocardial Infarction in the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries Trial Circulation, May 16, 2000; 101(19): 2231 - 2238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Thiemann, J. Coresh, S. P. Schulman, G. Gerstenblith, W. J. Oetgen, and N. R. Powe Lack of Benefit for Intravenous Thrombolysis in Patients With Myocardial Infarction Who Are Older Than 75 Years Circulation, May 16, 2000; 101(19): 2239 - 2246. [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]
|
|
|
|
|
|
D. R. Holmes Jr, P. B. Berger, J. S. Hochman, C. B. Granger, T. D. Thompson, R. M. Califf, A. Vahanian, E. R. Bates, and E. J. Topol Cardiogenic Shock in Patients With Acute Ischemic Syndromes With and Without ST-Segment Elevation Circulation, November 16, 1999; 100(20): 2067 - 2073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N G Mahon, C O'Rorke, M B Codd, H A McCann, K McGarry, and D D Sugrue Hospital mortality of acute myocardial infarction in the thrombolytic era Heart, May 1, 1999; 81(5): 478 - 482. [Abstract] [Full Text]
|
|
|
|
|
|
D. R. Holmes Jr., H. D. White, K. S. Pieper, S. G. Ellis, R. M. Califf, and E. J. Topol Effect of age on outcome with primary angioplasty versus thrombolysis J. Am. Coll. Cardiol., February 1, 1999; 33(2): 412 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R McMechan and A A J. Adgey Age related outcome in acute myocardial infarction BMJ, November 14, 1998; 317(7169): 1334 - 1335. [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
H. D. White and F. J. J. Van de Werf Thrombolysis for Acute Myocardial Infarction Circulation, April 28, 1998; 97(16): 1632 - 1646. [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]
|
|
|
|
 |
|
 The Continuous Infusion versus Double-Bolus Admini A Comparison of Continuous Infusion of Alteplase with Double-Bolus Administration for Acute Myocardial Infarction N. Engl. J. Med., October 16, 1997; 337(16): 1124 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 THROMBOLYTIC THERAPY FOR THE ELDERLY: DOES ONE STRATEGY FIT ALL? Journal Watch (General), October 25, 1996; 1996(1025): 3 - 3. [Full Text]
|
|
|
|
|
|
P. M. Ridker and C. H. Hennekens Age and Thrombolytic Therapy Circulation, October 15, 1996; 94(8): 1807 - 1808. [Full Text]
|
|
|
|
|
|
C. Napoli, G. Aldini, J. L. Wallace, F. de Nigris, R. Maffei, P. Abete, D. Bonaduce, G. Condorelli, F. Rengo, V. Sica, et al. Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosis PNAS, February 5, 2002; 99(3): 1689 - 1694. [Abstract] [Full Text] [PDF]
|
|