Multiple clinical trials have been undertaken to understand better the events leading to
unstable angina and non-Q wave
myocardial infarction. Some of these studies focused on evaluating the role of antithrombotic
therapy; others evaluated the role of more aggressive invasive treatment versus medical
therapy. In the 1980s and 1990s, studies revealed that antithrombotic
therapy with either acetylsalicyclic
acid alone or
heparin alone was more effective than placebo. The
Thrombosis in
Myocardial Infarction (TIMI) IIIB study attempted to compare medical
therapy with early surgical intervention, reporting that early intervention did not result in any significant improvement in patient outcome over medical
therapy. In the mid- to late 1990s, the
thrombin hypothesis was introduced, suggesting that
thrombin antagonists would arrest the coagulation and thrombotic cascade. The Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO) IIb study put the
thrombin hypothesis to the test, and it found that there was no significant difference between
hirudin and
unfractionated heparin treatments after 30 days.
Glycoprotein IIb/IIIa receptor antagonists were then researched in the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC), the
c7E3 Fab Antiplatelet
Therapy in Unstable Refractory angina (CAPTURE), the Platelet IIb/IIIa Antagonism for the Reduction of
Acute coronary syndrome events in a Global Organization Network (
PARAGON) and the Platelet Receptor Inhibition of Ischemic Syndrome Management in Patients Limited to
Unstable Angina Signs and Symptoms (PRISM-PLUS) studies, shifting the attention to the platelet. These studies gave contrasting results, bringing to the foreground the issues of optimal use of
antithrombotic agents and proper timing of surgical intervention. Medical
therapy for
unstable angina and non-Q wave
myocardial infarction was addressed in the Efficacy and Safety of Subcutaneous
Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) study, which compared a
low molecular weight heparin,
enoxaparin, with
unfractionated heparin. A significant difference in outcomes was found in favour of
enoxaparin.