Effectiveness of prolonged low dose recombinant tissue-type plasminogen activator for refractory unstable angina

The aim of the present study was to evaluate the effectiveness of prolonged administration of thrombolytic therapy with low doses of recombinant tissue-type plasminogen activator (rt-PA) in patients with refractory unstable angina. Intracoronary thrombosis is often the cause of instability in patients with unstable angina. Thrombolytic therapy has been tested in these patients with conflicting results. Sixty-seven patients with unstable angina refractory to standard antianginal therapy were randomized to receive, in addition to the common antianginal therapy, either rt-PA (0.03 mg/kg body weight per h for 3 consecutive days) plus heparin (to achieve activated clotting time of 250 to 400 s) (36 patients, group A) or the same dose of heparin plus placebo (31 patients, group B). No major bleeding was observed in either group of patients. One patient in group A and four in group B (2.7% vs. 12.9%, p < 0.01) developed acute myocardial infarction during the hospital period. Eight patients in group B underwent emergency coronary artery surgery or angioplasty because of worsening of symptoms. Group A patients had a significant reduction in the occurrence of chest pain compared with those in group B (95% confidence interval −7.2 to −2.1 episodes/3 days, p < 0.01). Patients in group B had a greater number of episodes of transient myocardial ischemia (237 vs. 103, p < 0.01) and a longer total ischemic burden (114 ± 23 vs. 45.6 ± 8.9 min/day, p < 0.01) than group A patients. After a mean follow-up of 14 ± 6 months, group A patients were more frequently angina free and had a lower incidence of readmission to the hospital than group B patients. The combination of heparin and protracted administration of rt-PA at low doses is effective in stabilizing and reducing in-hospital adverse events in patients with unstable angina refractory to antianginal therapy.