TISSUE PLASMINOGEN-ACTIVATOR IN REFRACTORY UNSTABLE ANGINA - A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL IN PATIENTS WITH REFRACTORY UNSTABLE ANGINA AND SUBSEQUENT ANGIOPLASTY

To evaluate the effect of recombinant tissue plasminogen activator (alteplase) on the clinical course, angiographic changes and the outcome of subsequent coronary angioplasty, 36 patients with angina at rest, despite bedrest and medical treatment including heparin, and with concomitant ECG changes, were studied. After diagnostic angiography, patients were randomized to receive either alteplase 100mg in 3 h (19 patients), or placebo (17 patients). The mean interval between qual anginal episode and initial angiography was 10 and 9 h for the alteplase and placebo group, respectively. Angiography was repeated and angioplasty was performed within 24 hours.Between the first and the second angiogram, five patients in the alteplase and seven in the placebo group had recurrent ischaemic episodes, while four alteplase and three placebo patients showed signs of myocardial necrosis (creatine kinase (CK) rise ≥twice the upper limit for normal). Intracoronary clots were recognized in three alteplase patients and one placebo patient at the first angiograrn, while two alteplase patients and one placebo patient showed total occlusion of the ischaemic-related vessel. After infusion, thrombi were present in four alteplase patients and one placebo patient, and total occlusion in three alteplase patients and one placebo patient. Quantitative coronary angiography showed no change in the percentage diameter stenosis of the ischae, nia-related segment after drug infusion, (alteplase 67±16 to 69±16%; placebo 65±11 to 63±12%). Angioplasty was successful in 14 of 19 alteplase and 14 of 16 placebo patients. Three patients after alteplase and two placebo patients developed myocardial necrosis during percutaneous transluminal coronary angioplasty (PTCA) and one alteplase patient required urgent bypass surgery. Minor bleeding complications were observed in six alteplase patients before the second angiogram and in five alteplase patients and one placebo patient after PTCA. One patient after alteplase developed a fatal retroperitoneal haemorrhage.In patients with unstable angina refractory to medical treatment, including heparin, alteplase has no beneficial effect on the severity of coronary stenosis, on the clinical course, or on the success of a subsequent angioplasty procedure. Thus thrombolytic therapy with alteplase for unstable angina cannot be recommended on the basis of this investigation. © 1991 The European Society of Cardiology.