Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study Group.

BACKGROUND: Patients with unstable angina despite intensive medical therapy, ie, refractory angina, are at high risk for developing thrombotic complications: myocardial infarction or coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that blocks the platelet glycoprotein (GP) IIb/IIIa receptor and potently inhibits platelet aggregation. METHODS AND RESULTS: To evaluate whether potent platelet inhibition could reduce these complications, 60 patients with dynamic ST-T changes and recurrent pain despite intensive medical therapy were randomized to c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection followed by 10 micrograms/min for 18 to 24 hours until 1 hour after completion of second angiography and PTCA. During study drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay, 12 major events occurred in 7 placebo patients (23%), including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but in none of the c7E3 Fab patients. Quantitative analysis showed significant improvement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. Measurement of platelet function and bleeding time demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction of ex vivo platelet aggregation to ADP, and a significantly prolonged bleeding time during c7E3 Fab infusion, without excess bleeding. CONCLUSIONS: Combined therapy with c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support the concept that effective blockade of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and facilitate PTCA in patients with refractory unstable angina.

Prehospital thrombolysis with alteplase (rt-PA) in acute myocardial infarction.

The improvement in survival in patients undergoing thrombolytic therapy in myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPerfusion in Acute Infarction Rotterdam (REPAIR) study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, 'Actilyse'). A small portable ECG computer system is used to confirm the presence of a large myocardial infarction (at least 1.0 mV ST-deviation) 'on the spot'. Between 22 June 1988 and 1 January 1991, 226 patients were treated by the ambulance service after the evaluation of 9052 patients complaining of chest pain. Therapy could be initiated within an average of 100 +/- 56 min (SD) after the onset of symptoms, and within 22 +/- 9 min after ambulance arrival. Three patients were defibrillated during transportation. Six patients (3%) died after arrival in the hospital. The time gained by prehospital treatment was 47 min (95% confidence limits 44-51 min) in comparison with 220 patients who did not meet the criteria for prehospital thrombolysis, but received thrombolytic therapy as soon as possible after hospital admission. The developed procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician. The observed low mortality supports the concept that prehospital thrombolytic therapy is indeed beneficial to the patient.

[Earlier treatment of acute myocardial infarction with administration of alteplase (rt-PA) before hospitalization]. / Snellere behandeling van het acute myocardinfarct door toediening van alteplase (rt-PA) vóór opname.

The gain in survival by thrombolytic therapy in patients with myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPAIR study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, Actilyse). Indications and contraindications are verified by general practitioner or ambulance nurse with a short questionnaire. A small portable ECG computer system is used to confirm the presence of a large evolving myocardial infarction 'on the spot'. Between June 1988 and May 1990, 150 patients were treated by the ambulance service. Therapy could be initiated within an average of 91 (+/- 40) minutes (sd) after the onset of symptoms, and within 23 (+/- 9) minutes after ambulance arrival. Three patients were defibrillated during transportation, in one of these therapy had to be discontinued because of cardiac massage. No other complications were observed. Five patients (3%) died after arrival in the hospital. The time gained by prehospital treatment averaged 47 (+/- 2) minutes in comparison with 220 patients who received thrombolytic therapy after hospital admission. The procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician.