EFFECTIVENESS OF PROLONGED LOW-DOSE RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR FOR REFRACTORY UNSTABLE ANGINA

Objectives. The aim of the present study was to evaluate the effective ness of prolonged administration of thrombolytic therapy with low dose s of recombinant tissue-type plasminogen activator (rt-PA) in patients with refractory unstable angina. Background. Intracoronary thrombosis is often the cause of instability in patients with unstable angina. T hrombolytic therapy has been tested in these patients with conflicting results. Methods. Sixty-seven patients with unstable angina refractor y to standard antianginal therapy were randomized to receive, in addit ion to the common antianginal therapy, either rt-PA (0.03 mg/kg body w eight 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 dos e of heparin plus placebo (31 patients, group B). Results. No major bl eeding 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 myoca rdial 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 i n the occurrence of chest pain compared with those in group B (95% con fidence 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 ische mia (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 freque ntly angina free and had a lower incidence of readmission to the hospi tal than group B patients. Conclusions. The combination of heparin and protracted administration of rt-PA at low doses is effective in stabi lizing and reducing in-hospital adverse events in patients with unstab le angina refractory to antianginal therapy.