Ridogrel Versus Aspirin Patency Trial - RAPT

Description:

RAPT was a randomized trial of ridogrel, a combined thromboxane A2 synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor antagonist, versus aspirin in patients with acute myocardial infarction (MI) being treated with streptokinase.

Hypothesis:

Ridogrel will yield more complete inhibition of platelet aggregation than aspirin, resulting in superior clinical outcomes.

Study Design

Study Design:

Patients Enrolled: 907
Mean Follow Up: 14 days
Mean Patient Age: <76 years
Female: 15

Patient Populations:

Patients <76 years of age presenting to the hospital within six hours of onset of symptoms with ST segment elevation of ≥0.1 mV in one or more limb lead or ≥0.2 mV in one or more precordial leads.

Exclusions:

Treatment with aspirin or nonsteroidal anti-inflammatory drugs during the past seven days, treatment with heparin or anticoagulation at the time of admission, previous coronary artery bypass grafting, severe congestive heart failure, or usual contraindications to thrombolysis

Primary Endpoints:

Coronary artery patency (TIMI II or III flow) at pre-discharge angiogram performed 7-14 days after admission

Secondary Endpoints:

Clinical markers of reperfusion at two hours defined as ≥50% reduction in subjective pain score, ≥50% reduction in ST-segment elevation, or a ≥100% increase in creatine kinase values from baseline; and cardiac events.

Drug/Procedures Used:

Patients with acute ST-segment elevation MI were randomized to receive either aspirin (250 mg IV bolus followed by 160 mg PO qd) or ridogrel (300 mg IV bolus followed by 300 mg PO bid). Patients first received 1.5 MU streptokinase infused over one hour, followed by administration of the study medication.

Concomitant Medications:

Additional use of aspirin or other antiplatelet medications was not allowed. Heparin was not allowed. All other medications were at the discretion of treating physician.

Principal Findings:

A total of 907 patients were randomized. At baseline, the groups were well matched in terms of age, gender, past medical history, and infarct-related vessel.

For the primary endpoint, a total of 577 patients had angiograms performed between 7 and 14 days postadmission. Of these, 75.5% in the aspirin group and 72.2% in the ridogrel group had TIMI 2 or 3 flow (p=NS). Both groups had similar rates of clinical events during hospitalization including death, stroke, reinfarction, and bleeding complications. The individual endpoint of ischemic stroke was lower in the ridogrel group than the aspirin group (0 events vs. 6 events, p<0.04).

Interpretation:

Among patients with ST-segment elevation MI treated with streptokinase, the combined thromboxane A2 synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor antagonist ridogrel was not associated with differences in vessel patency compared to aspirin. These results suggest that although ridogrel more effectively inhibits the arachidonic acid pathway, such inhibition may not be associated with improved clinical outcomes in acute MI.

References:

Randomized trial of ridogrel, a combined thromboxane A2 synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor antagonist, versus aspirin as adjunct to thrombolysis in patients with acute myocardial infarction. The Ridogrel Versus Aspirin Patency Trial (RAPT). Circulation 1994;89:588-95.

Clinical Topics: Dyslipidemia, Lipid Metabolism

Keywords: Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Streptokinase, Thromboxane A2, Receptors, Prostaglandin, Pyridines, Enzyme Inhibitors, Pentanoic Acids, Arachidonic Acid, Gastrointestinal Agents


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