Abstract
Because thrombus formation may contribute to coronary obstruction in patients with unstable angina pectoris, we performed a pilot investigation to determine whether thrombolytic therapy can relieve coronary narrowing in this acute ischemic syndrome. Sixty-seven patients with rest angina and angiographic evidence of coronary stenosis were randomly assigned to receive either low-dose intravenous recombinant tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 1 hour), high-dose intravenous rt-PA (0.75 mg/kg over 1 hour; total dose, 100 mg over 6 hours), or intravenous placebo followed by repeat coronary angiography at 24-48 hours to assess change in the severity of coronary narrowing. Each patient also received oral aspirin and intravenous heparin. Mean values of coronary stenosis severity (percent of diameter reduction) declined to a similar extent in each group: placebo, 75±14% to 72±14% (p=0.07); low-dose rt-PA, 75±16% to 71±18% (p=0.03), and high-dose rt-PA, 82±11% to 77±17% (p=0.18), with only the low-dose rt-PA group achieving statistical significance. Resolution of intracoronary filling defects, increase in antegrade flow grade, or both also occurred equally among the three groups. There was considerable variation in individual patient response. Between 29% and 50% of patients within each group demonstrated a decrease in stenosis severity, whereas 50% to 57% noted either improvement in antegrade flow or resolution of intracoronary thrombus. There was no difference in incidence of major bleeding events among the three groups. Thus, a combination of intravenous t-PA, aspirin, and heparin can reduce the severity of coronary stenosis in patients with unstable angina, but the treatment effect is mild in magnitude, varies among individual patients, and is not clearly superior to that achieved by the combination of aspirin and heparin alone.