Global Utilization of Streptokinase and TPA for Occluded Arteries-III - GUSTO-3

Description:

Alteplase vs. reteplase for 30-day mortality in acute MI.

Hypothesis:

To compare the efficacy and safety of alteplase and reteplase.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 15,059
Mean Follow Up: 6 months
Mean Patient Age: 63
Female: 27

Patient Populations:

30 minutes of continuous symptoms of acute myocardial infarction.
Presentation within 6 hours after the onset of symptoms.
ST-segment elevation of at least 1 mm in two or more limb leads, ST-segment elevation of at least 2 mm in the precordial leads, or bundle-branch block.

Exclusions:

Active bleeding
Stroke or central nervous system damage.
Recent major surgery.
Systolic blood pressure greater than 200 mm Hg or diastolic blood pressure greater than 110 mm Hg at any time after arrival.
Recent noncompressible vascular puncture.
Concomitant use of an oral anticoagulant with INR > 2

Primary Endpoints:

Mortality at 30 days.

Secondary Endpoints:

Net clinical benefit, defined as freedom from death or disabling stroke; death or nonfatal stroke.
Reinfarction.
Congestive heart failure
Mortality at 24 hours

Drug/Procedures Used:

Reteplase, in two bolus doses of 10 MU each given 30 minutes apart, or an accelerated infusion of alteplase, up to 100 mg infused over a period of 90 minutes.

Concomitant Medications:

Aspirin, heparin

Principal Findings:

Recombinant plasminogen activator (reteplase) is a mutant of wild-type tissue plasminogen activator. A total of 10,138 patients were randomized to reteplase, and 4921 patients were randomized to alteplase.

The mortality rate at 30 days was 7.47 percent for reteplase and 7.24 percent for alteplase (adjusted P = 0.54; odds ratio, 1.03; 95 percent confidence interval, 0.91 to 1.18). The 95 percent confidence interval for the absolute difference in mortality rates was -1.1 to 0.66 percent.

The similarity in the overall mortality data remained consistent across subgroups.

Stroke occurred in 1.64 percent of patients treated with reteplase and in 1.79 percent of those treated with alteplase (P = 0.50). The respective rates of the combined end point of death or nonfatal, disabling stroke were 7.89 percent and 7.91 percent (P = 0.97; odds ratio, 1.0; 95 percent confidence interval, 0.88 to 1.13).

Use of angiography, angioplasty, bypass surgery, and other major procedures did not differ significantly between the groups.

Interpretation:

The safety of reteplase bolus therapy was initially demonstrated in the INJECT trial through a comparison with streptokinase. The GUSTO III design assessed the relative efficacy of reteplase with alteplase. Compared with an accelerated infusion of alteplase, reteplase, although easier to administer, did not provide any additional survival benefit in the treatment of acute myocardial infarction. Other results, particularly for the combined end point of death or nonfatal, disabling stroke, were similar for the two plasminogen activators.

References:

1. N Engl J Med 1997;337:1118-23. Final results

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, EP Basic Science, Lipid Metabolism, Novel Agents

Keywords: Myocardial Infarction, Stroke, Streptokinase, Plasminogen Activators, Heparin, Recombinant Proteins, Bundle-Branch Block, Fibrinolytic Agents, Tissue Plasminogen Activator, Angioplasty


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