Sequential combination thrombolytic therapy for acute myocardial infarction: results of the Pro-Urokinase and t-PA Enhancement of Thrombolysis (PATENT) Trial.
OBJECTIVE
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 given 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.
Zarich
S W
SW
Cardiovascular Division, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Kowalchuk
G J
GJ
Weaver
W D
WD
Loscalzo
J
J
Sassower
M
M
Manzo
K
K
Byrnes
C
C
Muller
J E
JE
Gurewich
V
V
D000328:Adult; D000368:Aged; D015986:Confounding Factors, Epidemiologic; D017023:Coronary Angiography; D004792:Enzyme Precursors / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*; D014654:Vascular Patency / Q000187:drug effects
D004792:Enzyme Precursors; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase