FAILURE OF EPOPROSTENOL (PROSTACYCLIN, PGI(2)) TO INHIBIT PLATELET-AGGREGATION AND TO PREVENT RESTENOSIS AFTER CORONARY ANGIOPLASTY - RESULTS OF A RANDOMIZED PLACEBO-CONTROLLED TRIAL

Objective-To study the effect of epoprostenol (prostacyclin, PGI(2)) g iven before, during, and for 36 h after coronary angioplasty on resten osis at six months and to evaluate the transcardiac gradient of platel et aggregation before and after percutaneous transluminal coronary ang ioplasty (PTCA) in treated and placebo groups. Design-Double blind pla cebo controlled randomised study. Patients-135 patients with successfu l coronary angioplasty. Methods-Intravenous infusion of PGI(2) (4 ng/k g/ml) or buffer was started before balloon angioplasty and continued f or 36 hours. Platelet aggregation was measured in blood from the aorta and coronary sinus before and after PTCA in each group. Routine follo w up was at six months with repeat angiography and there was quantitat ive assessment of all angiograms (those undertaken within the follow u p period and at routine follow up). Presentation of results-Restenosis rates in treated and placebo groups determined according to the Natio nal Heart, Lung and Blood Institute definition IV. Comparison at follo w up between the effect of treatment on mean absolute luminal diameter and mean absolute follow up diameter in the placebo group. Comparison of acute gain and late loss between groups. Results-Of 125 patients a vailable for assessment 23 were re-admitted because of angina within t he follow up period. Quantitative angiography showed restenosis in 15 (10 in the PGI(2) group and five in the placebo group). Of 105 patient s evaluated at six month angiography there was restenosis in nine more in the PGI(2) group and 18 more in the placebo group. Total restenosi s rates (for patients) were 29.2% for PGI(2) and 38.3% for placebo (NS ). The mean absolute gain in luminal diameter was 1.84 (0.76) mm in th e PGI(2) group and 1.58 (0.56) mm in the placebo group (p = 0.04); the late loss in the PGI(2) group was also greater (0.65 (0.94) mm vs 0.6 2 (0.89) mm (NS) and there was no significant difference in final lumi nal diameter at follow up between the two groups (1.83 (0.88) mm v 1.5 9 (0.60) mm). The transcardiac gradient of quantitative platelet aggre gation increased after PTCA in both groups, indicating that PGI(2) in this dose did not affect angioplasty-induced platelet activation. Mean (SD) platelet activation indices in the PGI(2) group were pre PTCA ao rta 8.4 (4.1) v coronary sinus 8.8 (4.0) (p = 0.001) and post PTCA aor ta 8.9(3.0) v coronary sinus 12.9 (5.7) (p = 0.001). In the placebo gr oup the values were pre PTCA aorta 7.6 (3.3) v coronary sinus 7.4 (3.6 ) (p = 0.001) and post PTCA aorta 7.6(2.8) v coronary sinus 11.2(4.3) (p = 0.001). Conclusion-The dose of PGI(2) given was designed to limit side effects and as a short-term infusion did not significantly decre ase the six month restenosis rate after PTCA, The sample size, which w as determined by the original protocol and chosen because of the poten cy of the agent being tested, would have detected only a 50% reduction in restenosis rate. There was, however, no effect in the treated pati ents on the increased platelet aggregation seen in placebo group as a result of angioplasty. Angioplasty is a powerful stimulus to blood fac tor activation. Powerful agents that prevent local platelet adhesion a nd aggregation are likely to be required to reduce restenosis.