Characteristics and mortality outcomes of thrombolysis trial participants and nonparticipants: a population-based comparison

Institute for Clinical Evaluative Sciences in Ontario, Toronto, Canada.

OBJECTIVES: This study was done to compare characteristics and outcomes of patients with acute myocardial infarction participating in two thrombolysis trials with those of nontrial patients at study hospitals and external hospitals. BACKGROUND: Preferential recruitment of lower risk patients into randomized trials of thrombolysis has been suggested by earlier studies. However, to date there has not been a definitive population-based comparison of characteristics and outcomes for thrombolysis trial participants and nonparticipants. METHODS: Population-based data on hospital admissions and mortality from acute myocardial infarction for all hospitals in Ontario from 1989 to 1992 were linked to data on trial participants in two distinct thrombolysis studies (GUSTO I and LATE). Included were 1,304 patients entered into GUSTO, 12,657 nonparticipants at GUSTO hospitals, 249 patients entered into LATE, 5,997 nonparticipants at LATE hospitals and 12,299 patients at external hospitals. The main outcomes were differences in age, gender, comorbidity scores, coronary revascularization and survival to hospital discharge. RESULTS: Patients in both GUSTO and LATE were significantly more likely to be <70 years old (odds ratio [OR] 2.8 and 3.2, respectively), to be male (OR 2.0 and 2.1, respectively), to have low comorbidity scores (OR 2.0 and 2.3, respectively) and, for GUSTO alone, to undergo coronary revascularization (OR 2.4). Nontrial patients were similar between trial hospitals and external hospitals. In-hospital mortality rates for GUSTO and LATE patients were lower (6.9% and 6.6%, respectively) than for nonparticipants at study hospitals (16.8% and 19.7%, respectively; p<0.001 for both comparisons). Survival to hospital discharge remained higher among GUSTO (OR 1.9) and LATE patients (OR 2.0) than nonparticipants at study hospitals even after adjustment for age, gender, revascularization and comorbidity scores. CONCLUSIONS: Compared with nontrial patients, thrombolysis trial participants are younger, more often male, undergo more revascularization and have less comorbid disease. Even after adjustment for these factors, participants have a survival advantage over nonparticipants that is larger than expected from thrombolysis alone. These findings are not attributable to inferior care or skewed populations at hospitals that did not join these major trials. Further study of these selection biases may guide future trial design and deepen our understanding of why thrombolytics have been underused for high risk patients in routine practice.

This article has been cited by other articles:

				J. Travers, S. Marsh, M. Williams, M. Weatherall, B. Caldwell, P. Shirtcliffe, S. Aldington, and R. Beasley External validity of randomised controlled trials in asthma: to whom do the results of the trials apply? Thorax, March 1, 2007; 62(3): 219 - 223. [Abstract] [Full Text] [PDF]

				D. T. Ko, H. M. Krumholz, Y. Wang, J. M. Foody, F. A. Masoudi, E. P. Havranek, J. J. You, D. A. Alter, T. A. Stukel, A. M. Newman, et al. Regional Differences in Process of Care and Outcomes for Older Acute Myocardial Infarction Patients in the United States and Ontario, Canada Circulation, January 16, 2007; 115(2): 196 - 203. [Abstract] [Full Text] [PDF]

				P. G. Steg, J. Lopez-Sendon, E. Lopez de Sa, S. G. Goodman, J. M. Gore, F. A. Anderson Jr, D. Himbert, J. Allegrone, F. Van de Werf, and for the GRACE Investigators External Validity of Clinical Trials in Acute Myocardial Infarction Arch Intern Med, January 8, 2007; 167(1): 68 - 73. [Abstract] [Full Text] [PDF]

				Y. Gerber, J. P. McConnell, A. S. Jaffe, S. A. Weston, J. M. Killian, and V. L. Roger Lipoprotein-Associated Phospholipase A2 and Prognosis After Myocardial Infarction in the Community Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2517 - 2522. [Abstract] [Full Text] [PDF]

				D. A. Alter, D. T. Ko, A. Newman, and J. V. Tu Factors explaining the under-use of reperfusion therapy among ideal patients with ST-segment elevation myocardial infarction Eur. Heart J., July 1, 2006; 27(13): 1539 - 1549. [Abstract] [Full Text] [PDF]

				J West, J Wright, D Tuffnell, D Jankowicz, and R West Do clinical trials improve quality of care? A comparison of clinical processes and outcomes in patients in a clinical trial and similar patients outside a trial where both groups are managed according to a strict protocol Qual. Saf. Health Care, June 1, 2005; 14(3): 175 - 178. [Abstract] [Full Text] [PDF]

				C. J. Terkelsen, J. F. Lassen, B. L. Norgaard, J. C. Gerdes, T. Jensen, L. B.-H. Gotzsche, T. T. Nielsen, and H. R. Andersen Mortality rates in patients with ST-elevation vs. non-ST-elevation acute myocardial infarction: observations from an unselected cohort Eur. Heart J., January 1, 2005; 26(1): 18 - 26. [Abstract] [Full Text] [PDF]

				P. Kaul, P. W. Armstrong, W.-C. Chang, C. D. Naylor, C. B. Granger, K. L. Lee, E. D. Peterson, R. M. Califf, E. J. Topol, and D. B. Mark Long-Term Mortality of Patients With Acute Myocardial Infarction in the United States and Canada: Comparison of Patients Enrolled in Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I Circulation, September 28, 2004; 110(13): 1754 - 1760. [Abstract] [Full Text] [PDF]

				S. D. Wiviott, D. A. Morrow, P. D. Frederick, R. P. Giugliano, C.M. Gibson, C. H. McCabe, C. P. Cannon, E. M. Antman, and E. Braunwald Performance of the thrombolysis in myocardial infarction risk index in the National Registry of Myocardial Infarction-3 and -4: A simple index that predicts mortality in ST-segment elevation myocardial infarction J. Am. Coll. Cardiol., August 18, 2004; 44(4): 783 - 789. [Abstract] [Full Text] [PDF]

				U. N. Khot, M. B. Khot, C. T. Bajzer, S. K. Sapp, E. M. Ohman, S. J. Brener, S. G. Ellis, A. M. Lincoff, and E. J. Topol Prevalence of Conventional Risk Factors in Patients With Coronary Heart Disease JAMA, August 20, 2003; 290(7): 898 - 904. [Abstract] [Full Text] [PDF]

				S. S. Rathore, K. P. Weinfurt, C. P. Gross, and H. M. Krumholz Validity of a Simple ST-Elevation Acute Myocardial Infarction Risk Index: Are Randomized Trial Prognostic Estimates Generalizable to Elderly Patients? Circulation, February 18, 2003; 107(6): 811 - 816. [Abstract] [Full Text] [PDF]

				N. M. Caplice and B. J. Gersh Stem Cells to Repair the Heart: A Clinical Perspective Circ. Res., January 10, 2003; 92(1): 6 - 8. [Full Text] [PDF]

				A. Heiat, C. P. Gross, and H. M. Krumholz Representation of the Elderly, Women, and Minorities in Heart Failure Clinical Trials Arch Intern Med, August 12, 2002; 162(15): 1682 - 1688. [Abstract] [Full Text] [PDF]

				C. M. Bell and D. A. Redelmeier Mortality among Patients Admitted to Hospitals on Weekends as Compared with Weekdays N. Engl. J. Med., August 30, 2001; 345(9): 663 - 668. [Abstract] [Full Text] [PDF]

				D. A. Morrow, E. M. Antman, A. Charlesworth, R. Cairns, S. A. Murphy, J. A. de Lemos, R. P. Giugliano, C. H. McCabe, and E. Braunwald TIMI Risk Score for ST-Elevation Myocardial Infarction: A Convenient, Bedside, Clinical Score for Risk Assessment at Presentation : An Intravenous nPA for Treatment of Infarcting Myocardium Early II Trial Substudy Circulation, October 24, 2000; 102(17): 2031 - 2037. [Abstract] [Full Text] [PDF]

				W. J. Cantor, E. D. Peterson, J. J. Popma, J. P. Zidar, M. H. Sketch Jr., J. E. Tcheng, and E. M. Ohman Provisional stenting strategies: systematic overview and implications for clinical decision-making J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1142 - 1151. [Abstract] [Full Text] [PDF]

				G. C. Friesinger II and R. F. Smith Old age, left bundle branch block and acute myocardial infarction: a vexing and lethal combination J. Am. Coll. Cardiol., September 1, 2000; 36(3): 713 - 716. [Full Text] [PDF]

				J. L. Kaufman, R. Pelligra, A. L. Reingold, D. L. Sackett, H. T. Shapiro, E. M. Meslin, and B. Woodward Protection for Human Subjects in Medical Research JAMA, May 10, 2000; 283(18): 2387 - 2390. [Full Text] [PDF]

				S.T. Higano and B.J. Gersh Coronary angiography and outcome following acute myocardial infarction Eur. Heart J., May 1, 2000; 21(9): 707 - 709. [PDF]

				E. M. Antman and K. M. Kuntz The Length of the Hospital Stay after Myocardial Infarction N. Engl. J. Med., March 16, 2000; 342(11): 808 - 810. [Full Text]

				N Brown, M Melville, D Gray, T Young, A M Skene, R G Wilcox, and J R Hampton Relevance of clinical trial results in myocardial infarction to medical practice: comparison of four year outcome in participants of a thrombolytic trial, patients receiving routine thrombolysis, and those deemed ineligible for thrombolysis Heart, June 1, 1999; 81(6): 598 - 602. [Abstract] [Full Text]

				M. Gil, J. Marrugat, J. Sala, R. Masia, R. Elosua, X. Albert, A. Pena, J. Vila, M. Pavesi, and G. Perez Relationship of Therapeutic Improvements and 28-Day Case Fatality in Patients Hospitalized With Acute Myocardial Infarction Between 1978 and 1993 in the REGICOR Study, Gerona, Spain Circulation, April 6, 1999; 99(13): 1767 - 1773. [Abstract] [Full Text] [PDF]

				A. Melgarejo-Moreno, J. Galcera-Tomas, A. Garcia-Alberola, M. Valdes-Chavarri, F. J. Castillo-Soria, E. Mira-Sanchez, J. Gil-Sanchez, and J. Allegue-Gallego Incidence, Clinical Characteristics, and Prognostic Significance of Right Bundle-Branch Block in Acute Myocardial Infarction : A Study in the Thrombolytic Era Circulation, August 19, 1997; 96(4): 1139 - 1144. [Abstract] [Full Text]

				J. V. Tu, C. L. Pashos, C. D. Naylor, E. Chen, S.-L. Normand, J. P. Newhouse, and B. J. McNeil Use of Cardiac Procedures and Outcomes in Elderly Patients with Myocardial Infarction in the United States and Canada N. Engl. J. Med., May 22, 1997; 336(21): 1500 - 1505. [Abstract] [Full Text] [PDF]