Author + information
- Eric J. Topol, MD, FACC†,1,
- Douglas C. Morris, MD, FACC‡,
- Richard W. Smalling, MD, PhD, FACC§,
- Richard R. Schumacher, MD, FACC‖,
- Charles R. Taylor, MD‖,
- Akira Nishikawa, MD§,
- Henry A. Liberman, MD‡,
- Désiré Collen, MD, PhD#,
- Margaret E. Tufte, BS**,
- Elliott B. Grossbard, MD** and
- William W. O’Neill, MD†
- ↵1Address for reprints: Eric J. Topol, MD, University of Michigan Medical Center, UH Bl F245, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109-0022.
A new, predominantly single chain preparation of recombinant tissue-type plasminogen activator was evaluated to determine coronary thrombolytic efficacy in 100 patients with acute myocardial infarction. At 3.6 ± 1.2 hours (mean ± SD) from symptom onset, patients received either intravenous tissue plasminogen activator (1.25 mg/kg body weight over 3 hours) or placebo on a 3:1 randomized, double-blind basis. Coronary angiography, performed 68 ± 13 minutes after initiation of the study drug infusion, demonstrated patency of the infarct-related artery in 40 (57%) of 70 patients in the tissue plasminogen activator group compared with 3 (13%) of 23 patients in the placebo group (p < 0.001). Patients in the placebo group were then eligible to receive intracoronary streptokinase. At 90 minutes the patency was observed in 49 (69%) of 71 tissue plasminogen activator patients compared with 5 (24%) of 21 placebo patients (p < 0.001). At 120 minutes patency was observed in 59 (79%) of 75 patients of the tissue plasminogen activator group and in 10 (40%) of 25 in the intracoronary streptokinase/placebo group.
A nadir value of < 100 mg/dl fibrinogen occurred in 8 (11%) of 73 patients receiving tissue plasminogen activator versus 8 (40%) of 20 patients treated with intracoronary streptokinase (p = 0.002). Moderate or severe bleeding episodes occurred in 39% of patients treated with tissue plasminogen activator compared with 32% of patients who received placebo/intracpronary streptokinase (p = NS). Thus, this tissue plasminogen activator preparation achieves a high rate of recanalization and, at the doses employed, exhibits increased fibrinogen sparing compared with intracoronary streptokinase.
↵† From the Division of Cardiology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan
↵‡ From the Department of Medicine, Emory University School of Medicine, Crawford W. Long Memorial Hospital, Atlanta, Georgia
↵§ From the University of Texas Health Science Center, Houston, Texas
↵‖ From the Methodist Hospital, Indianapolis, Indiana
↵# From the Department of Biochemistry, University of Vermont, Burlington, Vermont
↵** From the Genentech, Inc., South San Francisco, California.
* A list of the participating centers and collaborators appears in the Appendix.
- American College of Cardiology Foundation