High levels of platelet inhibition with abciximab despite heightened platelet activation and aggregation during thrombolysis for acute myocardial infarction - Results from TIMI (thrombolysis in myocardial infarction) 14

Background-We evaluated platelet activation and aggregation in patients wit h acute myocardial infarction (AMI) treated with thrombolytic therapy alone or with reduced-dose thrombolysis and concomitant abciximab. Methods and Results-The study was pet-formed in 20 control subjects and 51 patients with AMI before and after reperfusion with either alteplase or ret eplase or reduced doses of these agents with concomitant abciximab, Platele t activation was assayed by platelet surface expression of P-selectin. Turb idometric platelet aggregation in response to ADP was measured in patients before thrombolytic therapy and 90 minutes and 24 hours after the beginning of thrombolytic therapy. P-selectin expression was greater at baseline in patients than normal control subjects (30.4% versus 9.8%, P<0.0001) but was identical between the 2 groups after stimulation with ADP (64.4% versus 69 .3%, P=0.37). However, at 24 hours, basal P-selectin expression declined in patients (P=0.0025 versus baseline), whereas ADP-stimulated P-selectin exp ression was lower in patients than in control subjects (48% versus 69%, P=0 .0004). When combined with reduced doses of either alteplase or reteplase, abciximab achieved 91% and 83% inhibition of 5 and 20 mu mol/L ADP-induced platelet aggregation, which decreased to 46% and 40%, respectively, at 24 h ours. No appreciable difference in the platelet inhibition profile of abcix imab was observed between the 2 thrombolytics. Conclusions-Platelet activation and aggregation are heightened in the setti ng of thrombolysis fur AMI. Despite this enhanced level of platelet activat ion, abciximab, combined with a reduced-dose thrombolytic, inhibited platel et aggregation similarly to the level reported in elective settings.