Inhibition of platelet function by abciximab or high-dose tirofiban in patients with STEMI undergoing primary PCI: a randomised trial

Abstract

Background. In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, few data exist on the magnitude of platelet activation, aggregation and dosing of glycoprotein (GP) IIb/IIIa receptor inhibitors. Methods. Sixty STEMI patients were randomised to abciximab, to high-dose tirofiban or to no additional GP IIb/IIIa inhibitor treatment. Platelet activation (P-selectin expression) was measured using flow cytometry and the level of inhibition of platelet aggregation was assessed using the Plateletworks assay. Additionally, the PFA-100 with the collagen/adenosine-diphosphate cartridge (CADP) was used to compare the levels of platelet inhibition. All measurements were performed at baseline (T 0 ), immediately after (T 1 ), 30 minutes (T 2 ), 60 minutes (T 3 ) and 120 minutes (T 4 ) after primary PCI. Results. The level of platelet activation in both GP IIb/IIIa receptor inhibitor treated groups was significantly lower compared with the control group at all time points after primary PCI (p=0.04).Also the administration of the currently recommended dose of abciximab resulted in significantly lower levels of inhibition of aggregation compared with high-dose tirofiban (p<0.0001). In addition, the CADP closure times were significantly prolonged in both GP IIb/IIIa inhibitor treated groups compared with the control group at time points T 1 (p=0.006) and T 4 (p<0.0001).

Benefits From Small Molecule Administration as Compared With Abciximab Among Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Angioplasty

“…Of the 865 potentially relevant articles initially screened, a total of 7 trials were initially identified (6 -12). One trial was excluded because no data were available on clinical outcome (the first author was contacted) (9). Thus, a total of 6 trials were finally included in the meta-analysis ( Fig.…”

Would Tirofiban Have Been Shown Non‐Inferior to Abciximab Had the TENACITY Trial Not Been Terminated for Financial Reasons?

“…However, a high‐bolus‐dose regimen of tirofiban (25 μg/kg over 3 minutes, followed by a 0.15 μg/kg per minute maintenance infusion) has been found to have levels of platelet aggregation inhibition similar to those achieved by abciximab. Data from 15 clinical studies since 2003 suggest excellent efficacy, equivalent to that achieved by abciximab, and subsequent randomized trials comparing high‐bolus‐dose tirofiban with abciximab have, both individually and collectively, suggested that tirofiban is at least as effective as abciximab (Table ) . In placebo‐controlled trials, tirofiban has been shown superior to placebo at a degree similar to that which abciximab was shown to outperform placebo in trials leading to its approval by the FDA.…”

Safety and Efficacy of Tirofiban as an Adjunctive Therapy for Patients with St-Elevation Myocardial Infarction: A Comparison Versus Placebo and Abciximab

“…Two small studies previously showed similarities between the high dose of tirofiban and abciximab in platelet inhibition [26,35]. Another study [33] found similar rates of TIMI-3 flow after PCI and similar ventricular function recovery at 30 days between tirofiban and abciximab.…”

“…In the study by Ernst et al, [26], when platelet inhibition was measured in 112 STEMI patients who were either administered the standard dose of abciximab or one of two doses of tirofiban(10 g/kg bolus or the high-dose bolus regimen, 25 g/kg),mean periprocedural platelet inhibition exceeding 80% was only seen with the high-dose tirofiban regimen, which might make tirofiban a useful alternative for STEMI patients undergoing primary angioplasty. Several trials have assessed the role of tirofiban in primary angioplasty [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] ( Table 2). These studies have included patients treated with the standard 10 g/kg bolus and high-dose bolus regimens, as well as a nearly (upstream) administration and a downstream one.…”