Comparison Trial of Saruplase and Streptokinase - COMPASS

Description:

The goal of the Comparison Trial of Saruplase and Streptokinase (COMPASS) was to demonstrate the equivalence of saruplase to streptokinase in the treatment of patients with ST-segment elevation myocardial infarction (STEMI).

Hypothesis:

Saruplase, a recombinant, unglycosylated, human, single-chain urokinase-type plasminogen activator, would be similar in efficacy and safety to streptokinase in the treatment of patients with STEMI.

Study Design

Study Design:

Patients Enrolled: 3,089
Mean Follow Up: 30 days
Mean Patient Age: >20 years
Female: 20

Patient Populations:

Age >20 years old with nitrate-resistant chest pain lasting for ≥30 minutes, with ST-segment elevation >0.1 mV in two or more frontal plane leads or >0.2 mV in two or more precordial leads, and presentation within six hours after the onset of symptoms

Exclusions:

Severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >100 mm Hg on admission or hypertensive retinopathy grade III or IV) or known intracranial, gastrointestinal, clotting, hepatic, pulmonary, renal, urogenital, vascular, or other disorders that could increase the risk of bleeding after thrombolysis. Patients with major trauma or surgical procedures within one month were excluded, as were those with malignancy or known sensitivity to streptokinase or exposure to streptokinase within the past year or streptococcal infection within the past three months.

Primary Endpoints:

Death from any cause at 30 days after the start of study treatment

Secondary Endpoints:

Stroke, reinfarction, and reintervention at 30 days. In-hospital endpoints were bleeding, hypotension, and allergic reactions.

Drug/Procedures Used:

Eligible patients were randomized to receive heparin (5000 IU initial bolus) and saruplase (20 mg initial intravenous [IV] bolus followed by 60 mg IV over the next 60 minutes) or streptokinase (1.5 MU IV over 60 minutes) without the initial heparin bolus.

Concomitant Medications:

Oral or IV aspirin (200-400 mg initially followed by a maintenance dose of ≥75 mg daily thereafter). Thirty minutes after the completion of the initial 60-minute infusions of streptokinase or saruplase, heparin was administered to all patients for ≥24 hours and titrated to achieve a target activated partial thromboplastin time of 1.5-2.5 times the control value.

Principal Findings:

Saruplase was equivalent to streptokinase in the primary endpoint of death at 30 days (5.7% vs. 6.7%; odds ratio 0.84, p<0.01 for equivalence). Hypotension occurred less frequently in the saruplase group (31.4% vs. 38.1%, p=0.001), whereas hemorrhagic strokes were more common with saruplase than with streptokinase (0.9% vs. 0.3%, p=0.38). There was no significant difference between the saruplase and streptokinase groups in bleeding complications (10.4% vs. 10.9%, p=NS).

Interpretation:

Among patients with STEMI, saruplase was equivalent to streptokinase in the incidence of the primary endpoint of death at 30 days. Patients treated with saruplase were less likely to develop hypotension, but more likely to develop hemorrhagic stroke than those treated with streptokinase. The overall bleeding rates between the two treatment groups were similar. These findings suggest that saruplase is as effective as streptokinase in the treatment of acute STEMI, with a similar safety profile.

References:

Tebbe U, Michels R, Adgey J, et al. Randomized, double-blind study comparing saruplase with streptokinase therapy in acute myocardial infarction: the COMPASS Equivalence Trial. Comparison Trial of Saruplase and Streptokinase (COMPASS) Investigators. J Am Coll Cardiol 1998;31:487–93.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism, Novel Agents

Keywords: Myocardial Infarction, Stroke, Streptokinase, Urokinase-Type Plasminogen Activator, Chest Pain, Heparin, Recombinant Proteins, Hypotension, Fibrinolytic Agents, Hemorrhage


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