Therapeutic Delay and Reduced Functional Status Six Months After Thrombolysis for Acute Myocardial Infarction Jerry Avorn, MD, Eric Knight, MD, MPH, David A. Ganz, MD, MPH, and Sebastian Schneeweiss, MD, ScD Thrombolytic therapy decreases the mortality rate in patients with acute myocardial infarction (AMI), and the timing of thrombolysis has proved to be critical for de- creasing the short-term mortality rate. Much less is known about the longer term consequences of delays in thrombolysis, particularly for outcomes other than the mortality rate. We assessed the effect of time to throm- bolysis and other clinical predictors on cardiac func- tional status 6 months after AMI. We used InTIME II, a multicenter trial, to test the efficacy of alteplase and lanoteplase. This component of the trial was conducted in 147 North American centers. Patients were >18 years of age with ST-elevated AMI. Functional status was measured by the Duke Activity Status Index, which was administered 6 months after AMI. After multivariate adjustment for baseline characteristics, delay in presen- tation to hospital and delay in initiation of thrombolysis were significantly and independently associated with decreased cardiac functional status 6 months later. Each additional hour from symptom onset to hospital presen- tation was associated with a 16% increase (95% confi- dence interval 3% to 31%) in the likelihood of functional impairment (Duke Activity Status Index score <30). In addition, each additional delay of 1 hour from hospital presentation to thrombolysis independently increased the probability of functional impairment by 38% (12% to 71%). Thus, in patients with AMI, earlier presentation to the hospital and more rapid initiation of thrombolysis could prevent significant decreases in functional status months after the initial infarct. 2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:415– 420) W e measured the effect of time to treatment on functional status 6 months later in patients with acute myocardial infarction (AMI) who underwent thrombolysis. Although considerable attention has been paid to comparisons of 1 thrombolytic with an- other, much less is known about other aspects of thrombolytic use, including how effectively any agent in this class is deployed in routine clinical settings and the long-term consequences of such “systems” factors on the natural history of patients with AMI. METHODS Study population: The Intravenous NPA for the Treatment of Infarcting Myocardium Early (InTIME II) trial enrolled patients with ST-elevated myocardial infarction within 6 hours of symptom onset at 800 hospitals worldwide. It was initially designed to com- pare the 30-day mortality rate with 2 thrombolytics, alteplase and lanoteplase. All patients received aspirin and heparin. Eligible patients were 18 years of age with chest pain and ST elevation or left bundle branch block on the qualifying electrocardiogram. Exclusion criteria included cardiogenic shock, systolic blood pressure 180 mm Hg, diastolic blood pressure 110 mm Hg, any history of cerebrovascular disease, or increased risk of severe bleeding. Full details of the study methods have been reported elsewhere. 1 Insti- tutional review boards at each participating center approved the study. No significant difference in mor- tality rate was found between the 2 thrombolytics, but lanoteplase was associated with an increased rate of intracerebral hemorrhage 2 and was never marketed. We undertook the present analysis to determine the relation between functional status outcomes and delay between initial symptom presentation and thromboly- sis, independent of the thrombolytic agent used. It was conducted in the 147 North American centers that administered the Duke Activity Status Index (DASI) instrument to study participants. 3 These centers to- gether enrolled 2,167 patients. End points: The primary end point of this study was cardiac functional status 6 months after AMI as mea- sured by the DASI. 3 In this instrument, patients are asked whether they can perform specific activities without difficulty, ranging from being able to eat, dress, or bathe by themselves to being able to partic- ipate in strenuous sports. The DASI was developed to measure functional status and quality of life in patients with heart disease and has been frequently used in From the Division of Pharmacoepidemiology and Pharmacoeconom- ics, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. This study was supported by an unrestricted research grant from the Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey. The sponsor had no role in the design of this aspect of the study or in the analysis of data or interpretation and presentation of the findings. Manuscript received November 13, 2003; revised manuscript received and accepted April 16, 2004. Address for reprints: Jerry Avorn, MD, Division of Pharmacoepide- miology and Pharmacoeconomics, Brigham and Women’s Hospital, 1620 Tremont Steet, Suite 3030, Boston, Massachusetts 02120. E-mail: javorn@partners.org. 415 ©2004 by Excerpta Medica, Inc. All rights reserved. 0002-9149/04/$–see front matter The American Journal of Cardiology Vol. 94 August 15, 2004 doi:10.1016/j.amjcard.2004.04.055