Reteplase vs Alteplase Patency Investigation During Myocardial Infarction - RAPID-2


Reteplase vs. alteplase for angiographic patency in acute MI.


To determine whether a double-bolus regimen of reteplase could improve 90-minute coronary artery patency rates achieved with an "accelerated" front-loaded infusion of alteplase.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 324
Mean Follow Up: 35 days
Mean Patient Age: 60
Female: 22

Patient Populations:

Age >18
>30 minutes typical chest pain not relieved by nitroglycerin
ST elevation >0.1 mV in two of three inferior or lateral leads or >0.2 mV in at least two contiguous precordial leads or left bundle branch block
Presentation within 12 hours after onset of ischemic chest pain


Prior coronary artery bypass graft surgery
Previous stroke or known intracranial structural abnormalities
Previous percutaneous transluminal coronary angioplasty within 2 weeks
Previous Q-wave myocardial infarction in the same anatomic region as the qualifying infarction
Severe hypertension (> 180/110 mmHg)
Previous puncture of a noncompressible vessel within 2 weeks
Major surgery or active or potential internal bleeding in the previous 3 months

Primary Endpoints:

Infarct related coronary artery patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) at 90 minutes

Secondary Endpoints:

Coronary TIMI flow grade at 30 and 50 minutes and 5 to 14 days after therapy.
Left ventricular function at 90 minutes and 5 to 14 days after therapy.
Stroke, reinfarction, heart failure, recurrent angina/ishchemia, and coronary interventions within 35 days.

Drug/Procedures Used:

Reteplase, as a 10-MU bolus followed by 10 MU 30 minutes later, or front-loaded alteplase.

Principal Findings:

At 90 minutes, infarct related coronary artery patency (TIMI grade 2 or 3) was significantly higher for reteplase-treated patients compared to front-loaded alteplase-treated patients (83.4% versus 73.3%, P = .03).

At 90 minutes, complete patency (TIMI grade 3) also favored reteplase compared to alteplase (59.9% versus 45.2%, P = .01).

Reteplase-treated patients required fewer acute additional coronary interventions (13.6% versus 26.5%, P < .01)

The sum of catastrophic events, death, or nonfatal disabling stroke within 35 days, was 5.3% for reteplase and 9.0% for alteplase treated patients.

The composite endpoint of unsatisfactory outcome at 35 days after treatment (comprising death, reinfarction, congestive heart failure, or shock) was present in 21.3% of reteplase-treated patients compared to 22.6% of alteplase-treated patients.

There was no significant difference between groups for 35-day mortality ( 4.1% for reteplase, 8.4% for alteplase), bleeding requiring transfusion (12.4% versus 9.7%), or hemorrhagic stroke (1.2% versus 1.9%).


Reteplase, when given as a double bolus of 10 plus 10 million units to patients with acute myocardial infarction, achieved significantly higher rates of early reperfusion of the infarct-related coronary artery. Patients receiving reteplase required significantly fewer acute coronary interventions than those receiving alteplase without an apparent increased risk of complications. In both RAPID studies, mortality was lower and other outcomes were more favorable in reteplase recipients. These hypotheses were tested further in the GUSTO III trial.


1. Circulation 1996;94:891-8. Final results

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, EP Basic Science, Lipid Metabolism, Acute Heart Failure

Keywords: Myocardial Infarction, Stroke, Heart Failure, Recombinant Proteins, Bundle-Branch Block, Fibrinolytic Agents, Coronary Vessels, Tissue Plasminogen Activator, Hemorrhage, Nitroglycerin

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