Author + information
- Received October 12, 1994
- Revision received March 13, 1995
- Accepted March 28, 1995
- Published online August 1, 1995.
- Stuart W. Zarich, MD, FACC1,a,
- Glen J. Kowalchuk, MD, FACCb,
- W.Douglas Weaver, MD, FACCc,
- Joseph Loscalzo, MD, PhD, FACCd,
- Michael Sassower, MDa,
- Karen Manzo, RNa,
- Christine Byrnes, BSa,
- James E. Muller, MD, FACCa and
- Victor Gurewich, MDa
- ↵1Address for correspondence: Dr. Stuart W. Zarich, Cardiovascular Division, Institute for the Prevention of Cardiovascular Disease, Kennedy Building, Deaconess Hospital, One Deaconess Road, Boston, Massachusetts 02215.
Objectives. The present study was designed to test the efficacy and safety of a sequential combination of recombinant tissue-type plasminogen activator (rt-PA) and pro-urokinase in patients with acute myocardial infarction.
Background. Efforts continue to identify a thrombolytic regimen that induces rapid, complete and sustained coronary artery patency in acute myocardial infarction. The two endogenous plasminogen activators rt-PA and pro-urokinase have been shown experimentally to induce fibrinolysis by sequential and complementary mechanisms. As a result, certain combinations of these activators have been found to be synergistic in vitro and in vivo.
Methods. In a multicenter observational study with core facilities for angiographic and laboratory analysis, 101 patients with acute myocardial infarction were enrolled and gives a low dose bolus of rt-PA (5 to 10 mg) followed by a 90-min infusion of pro-urokinase (40 mg/h). All patients received intravenous heparin and oral aspirin. Coronary angiography was performed in all patients at 90 min.
Results. Angiography at 90 min showed the infarct-related artery to be patent (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) in 77% of patients, and 60% achieved TIMI grade 3 flow. At one center, angiography was repeated at 24 h to detect a possible reocclusion. All 28 patients with a patent infarct-related artery at 90 min had patency at 24 h (82% achieved TIMI grade 3 flow). Treatment was well tolerated, with bleeding complications essentially confined to arterial puncture site hematomas. There was only one in-hospital death.
Conclusions. A sequential combination of low dose rt-PA and reduced-dose pro-urokinase produced a high TIMI 3 patency rate, was well tolerated and was associated with a low reocclusion rate.
☆ This study was funded by a research grant from Farmitalia Carlo Erba, Milan, Italy. A complete list of co-investigators and participating institutions in the PATENT trial appears in the Appendix.
- Received October 12, 1994.
- Revision received March 13, 1995.
- Accepted March 28, 1995.