Recombinant Plasminogen Activator Angiographic Phase II International Dose-finding Study - RAPID-1


Reteplase vs. alteplase for angiographic patency in acute MI.


To compare bolus administration of r-PA to standard-dose alteplase (TPA) in achieving 90 minute infarct-related artery patency.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 606
Mean Patient Age: 57
Female: 23
Mean Ejection Fraction: 50%

Patient Populations:

18 to 75 years old
At least 30 minutes of typical chest pain not relieved by nitroglycerin
Presenting <6 hours after onset of chest pain
ST-segment elevation of 0.1 mV in the inferior or lateral leads or 0.2 mV in the precordial leads


Left bundle branch block
Prior coronary bypass surgery
Previous Q-wave myocardial infarction in the same anatomic region
Previous percutaneous transluminal coronary angioplasty (PTCA) within 2 weeks
Previous cerebral vascular accident
Severe hypertension with a systolic blood pressure >180 or diastolic blood pressure >110 mm Hg at presentation

Primary Endpoints:

TIMI grade 2 or 3 patency at coronary arteriography 90 minutes after initiation of thrombolytic therapy.

Secondary Endpoints:

TIMI 2 or 3 patency at 30 and 60 minutes and 5 to 14 days after initiation of thrombolytic therapy, as well as reocclusion within 5 to 14 days after administration of thrombolytic therapy and global (ejection fraction, EF) and regional (infarct zone) function at hospital admission and discharge.

Drug/Procedures Used:

TPA 100mg IV over 3 hours; r-PA as a 15-MU single bolus, r-PA as a 10-MU bolus followed by 5 MU 30 minutes later; or r-PA as a 10-MU bolus followed by 10 MU 30 minutes later.

Concomitant Medications:

Soluble aspirin ( 200 to 325 mg); heparin.

Principal Findings:

Of the 606 patients enrolled, 154 were randomized to 100 mg tPA, 146 to 15 MU rPA, 152 to 10+5 r-PA, and 154 patients to 10+10 MU r-PA

Coronary arteriography was performed at 30, 60, and 90 minutes after initiation of treatment and at hospital discharge.

The 10+10-MU r-PA group achieved better 90-minute TIMI 3 flow than the TPA group (63% vs 49%, P=.019). The TIMI 3 flow in the 10+10-MU r-PA group at 60 minutes was equivalent to that in the TPA group at 90 minutes (51 versus 49%).

TIMI-3 flow was also better for the 10+10-MU r-PA group at 5 to 14 days compared to controls (88% vs 71% P<.001)

Global ejection fraction in the 10+10-MU r-PA group was superior to the TPA group at hospital discharge (53±1.3% versus 49±1.3%, P=.034).

The 15-MU and 10+5-MU r-PA patency and left ventricular function results were similar to those of the TPA and inferior to those of the 10+10-MU r-PA group. Bleeding complications were similar between the groups.

The 30-day mortality rate in the 10+10-MU group was 1.9% compared with 3.9% in the TPA group. There was only one stroke in the r-PA groups (1/452) compared with six in the TPA group (6/154). The incidence of stroke in the 10+10-MU r-PA group was less than that observed in the TPA group (P=.03). The reinfarction rate and the incidence of congestive heart failure were similar between the groups.


Recombinant plasminogen activator (r-PA, reteplase) is a mutant of wild-type TPA. Reteplase given as a double bolus of 10+10 MU achieved more rapid, complete, and sustained thrombolysis of the infarct-related artery than standard-dose TPA, without an apparent increased risk of complications. TIMI 3 flow appeared to occur earlier after bolus administration of r-PA than with standard-dose TPA. The bleeding risks with all doses of r-PA were comparable to those associated with standard-dose TPA. The trial was open label and single blinded with envelope randomization, which may limit the broad generalizability of its results.

Although the RAPID trial was not designed to detect differences in mortality among the groups, clinical outcomes appeared favorable in reteplase recipients. These outcomes were assessed in the larger GUSTO-III trial.


1. Circulation 1995;91:2725-2732. Final results

Clinical Topics: Anticoagulation Management, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Lipid Metabolism, Novel Agents, Acute Heart Failure, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Stroke, Coronary Angiography, Ventricular Function, Left, Chest Pain, Plasminogen Activators, Heart Failure, Recombinant Proteins, Fibrinolytic Agents, Tissue Plasminogen Activator, Nitroglycerin

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