Author + information
- Received January 17, 1989
- Revision received March 13, 1989
- Accepted April 13, 1989
- Published online October 1, 1989.
- Eric J Topol, MD, FACC∗∗∗,
- Stephen G Ellis, MD, FACC∗,
- Robert M Califf, MD, FACC†,
- Barry S George, MD‡,
- David C Stump, MD§,
- Eric R Bates, MD, FACC∗,
- Elizabeth G Nabel, MD∗,
- Joseph A Walton, MD∗,
- Richard J Candela, MD†,
- Kerry L Lee, PHD†,
- Eva M Kline, RN∗,
- Bertram Pitt, MD, FACC∗,
- Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 4 Study Group∥
- ↵∗∗Address for reprintsEric J. Topol, MD, Division of Cardiology, B1-17245, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109-0022.
Current limitations of recombinant tissue-type plasminogen activator (rt-PA) therapy for acute myocardial infarction include failure to achieve recanalization in 25% of patients, reocclusion and reperfusion injury. IIoprost, a stable analogue of prostacyclin (PGIZ), has been demonstrated to facilitate thrombolysis and reduce myocardial stunning in experimental models. To evaluate combined therapy, rt-PA (100 mg 3 h) and IIoprost (2 ng/kg per min for 48 h) were administered to 25 patients and then rt-PA alone (same dose) was given to an additional 25 patients with evolving myocardial infarction. At 90 min after drug administration, infarct-related vessel patency was observed in 11 (44%) of 25 who received rt-PA plus Iloprost compared with 15 (60%) of 25 who received rt-PA alone (p = 0.26). At 1 week, reocclusion had occurred in 3 (14%) of 21 patients who received combined therapy compared with 6 (26%) of 23 patients treated with rt-PA alone (p = 0.46).
Ejection fraction increased significantly from baseline to 7 days for rt-PA alone whereas it decreased with combined therapy (rt-PA alone: 47.3 ± 11.5% at baseline to 50.4 ± 9.8% at 7 days; rt-PA plus Iloprost: 51.3 ± 10.1% at baseline to 49.0 ± 9.4% at 7 days; difference between groups p = 0.05). At 4 h after therapy, fibrinogen decreased 33% for rt-PA plus Iloprost compared with a 52% for rt-PA alone (p = 0.001). Fibrinogen degradation products increased 60% more for rt-PA alone than for rt-PA plus Iloprost. Thus, the combination of rt-PA plus Iloprost at the doses employed did not improve immediate or follow-up coronary artery patency or left ventricular functional recovery compared with that achieved with rt-PA alone.
↵∥ Coinvestigators and collaborating institutions are listed in the Appendix.
☆ This study was supported in part by Berlex Laboratories, Cedar Knoll, New Jersey and Grants HL-35058 and HL-01489 from the National Institutes of Health, Bethesda, Maryland. It was designed by the TAMI investigators in collaboration with Berlex Laboratories.
- Received January 17, 1989.
- Revision received March 13, 1989.
- Accepted April 13, 1989.