Combined tissue-type plasminogen activator and prostacyclin therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 4 Study Group

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.

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. Iloprost, a stable analogue of prostacyclin (PGI2), has been demonstrated to facilitate thrombolysis and reduce myocardial stunning in experimental models. To evaluate combined therapy, rt-PA (100 mg 3 h) and Iloprost (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 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 Ilprost. 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.

This article has been cited by other articles:

				I. George and M. C. Oz Myocardial Revascularization after Acute Myocardial Infarction Card. Surg. Adult, January 1, 2008; 3(2008): 669 - 696. [Full Text]

				D. C. Lee, W. Ting, and M. C. Oz Myocardial Revascularization after Acute Myocardial Infarction Card. Surg. Adult, January 1, 2003; 2(2003): 639 - 658. [Full Text]

				M. T. Roe, E. M. Ohman, A. C. P. Maas, R. H. Christenson, K. W. Mahaffey, C. B. Granger, R. A. Harrington, R. M. Califf, and M. W. Krucoff Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion J. Am. Coll. Cardiol., January 1, 2001; 37(1): 9 - 18. [Abstract] [Full Text] [PDF]

				E. M. Ohman, R. A. Harrington, C. P. Cannon, G. Agnelli, J. A. Cairns, and J.W. Kennedy Intravenous Thrombolysis in Acute Myocardial Infarction Chest, January 1, 2001; 119(2009): 253S - 277S. [Full Text] [PDF]

				K. W. Mahaffey, J. A. Puma, N. A. Barbagelata, M. F. DiCarli, M. A. Leesar, K. F. Browne, P. R. Eisenberg, R. Bolli, A. C. Casas, V. Molina-Viamonte, et al. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: Results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) Trial J. Am. Coll. Cardiol., November 15, 1999; 34(6): 1711 - 1720. [Abstract] [Full Text] [PDF]

				E. M. Ohman, N. S. Kleiman, G. Gacioch, S. J. Worley, F. I. Navetta, J. D. Talley, H. V. Anderson, S. G. Ellis, M. D. Cohen, D. Spriggs, et al. Combined Accelerated Tissue-Plasminogen Activator and Platelet Glycoprotein IIb/IIIa Integrin Receptor Blockade With Integrilin in Acute Myocardial Infarction: Results of a Randomized, Placebo-Controlled, Dose-Ranging Trial Circulation, February 18, 1997; 95(4): 846 - 854. [Abstract] [Full Text]

				J. J. Popma and E. J. Topol Adjuncts to Thrombolysis for Myocardial Reperfusion Ann Intern Med, July 1, 1991; 115(1): 34 - 44. [Abstract] [PDF]

				D. W. Krichbaum and D. A. Trivedi Thrombolytic Therapy in Acute Myocardial Infarction Journal of Pharmacy Practice, January 1, 1990; 3(5): 332 - 348. [PDF]