Randomized Trial of Aspirin, Sibrafiban, or Both for Secondary Prevention After Acute Coronary Syndromes - SYMPHONY II

Description:

Randomized Trial of Aspirin, Sibrafiban, or Both for Secondary Prevention After Acute Coronary Syndromes.

Hypothesis:

Assess the value of long-term sibrafiban, an oral glycoprotein IIb/IIIa inhibitor, following an acute coronary syndrome (ACS).

Study Design

Study Design:

Patients Enrolled: 8400

Drug/Procedures Used:

Initially designed as a double-blind trial in 8400 patients with ACS randomized to one of three treatment arms for 12-18 months: high-dose sibrafiban (HDS), low-dose sibrafiban (LDS) + 160 mg ASA and 160 mg ASA alone. The study was terminated when in a separate study short-term (90 days) sibrofiban was no better than ASA and possibly resulted in more sudden deaths. This trial was aborted early, and the primary end points of death, MI and severe recurrent ischemia were analyzed in the 6671 patients who completed a median of 90 days (range 65-160 days).

Principal Findings:

The average age was 59 years, and the qualifying event was an MI in 74% of each group. 98% were Killip class III or less on entry. The average time from qualifying event to first dose was 94 hours (range 63-132 hours). There was no difference in rate of composite primary end points between treatments (ASA 9.3%, LDS + ASA 9.2%, or HDS 10.5%). Death or MI (6.1% vs. 8.6%) occurred more often with HDS (OR 1.43) as did death and MI individually than ASA or LDS + ASA. Major bleeding was significantly more common in LDS + ASA than ASA alone (5.7% vs. 4.0%).

Combining ASA with LDS did not improve outcomes after acute coronary syndromes and caused more bleeding compared to ASA alone. There was a significant increase in events in the high-dose arm.

Interpretation:

The door has been closed on the present generation of oral Gp IIb/IIIa receptor inhibitors for acute coronary syndromes. In contrast to the well-established value of the IV preparations that decrease morbidity and mortality in ACS and enhance stent patency rates, evidence suggests each of the agents tested can result in increased thrombosis possibly by enhancing receptor activity during those hours when the drug is less active or not available.

References:

1. Second SYMPHONY Investigators. Circulation 2001;103:1727-33.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, ACS and Cardiac Biomarkers, Heart Failure and Cardiac Biomarkers, Interventions and ACS

Keywords: Acute Coronary Syndrome, Oximes, Piperidines, Platelet Aggregation Inhibitors, Thrombosis, Death, Sudden, Hemorrhage, Platelet Membrane Glycoprotein IIb, Stents, Platelet Glycoprotein GPIIb-IIIa Complex


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