Key result
Aspirin plus ticlopidine suppresses post-stent platelet activation, clarifying abciximab's lack of benefit on restenosis.
Why the study?
The ERASER study reported that potent platelet inhibition with abciximab does not reduce in-stent restenosis, prompting discussion of the role of background aspirin and ticlopidine therapy.
Abciximab does not reduce in-stent restenosis; leaves open αvβ3's role in neointimal hyperplasia.
We read with great interest the recent article by the Evaluation of ReoPro and Stenting to Eliminate Restenosis (ERASER) Investigators, in which it was reported that potent platelet inhibition with abciximab does not reduce in-stent restenosis. 1 Abciximab is an effective antithrombotic agent because of its ability to bind to glycoprotein IIb/IIIa (␣IIb/3) and to inhibit platelet aggregation.Abciximab also binds to a related integrin, ␣v3, which is also known as the vitronectin receptor.The functions of this receptor include cell adhesion, proliferation, and migration and platelet-mediated thrombin generation.Thus, abciximab is expected to provide platelet-mediated effects and ␣v3-mediated effects in vivo. 2 Previously, we investigated changes in coagulation and platelet activation in the coronary circulation induced by stent implantation. 3 Both aspirin and ticlopidine were administered to patients before stent implantation.Blood samples were drawn from the coronary sinus immediately before, immediately after, and 4 and 24 hours after stent implantation.Plasma levels of prothrombin fragment 1ϩ2 (F1ϩ2) and thrombin-antithrombin III complex (TAT), which are markers of coagulation activation, and levels of -thromboglobulin (-TG) and platelet factor 4 (PF4), which are markers of platelet disruption and activation, were measured.We found that F1ϩ2 and TAT levels in blood from the coronary sinus increased significantly 24 hours after stent implantation (F1ϩ2, from 0.73Ϯ0.05 to 1.00Ϯ0.10ng/mL; TAT, from 5.01Ϯ0.64 to 10.7Ϯ2.26 ng/mL).However, no significant changes in -TG and PF4 levels were observed after stent implantation (-TG, from 60.1Ϯ8.6 to 63.8Ϯ9.2 ng/mL; PF4, from 27.6Ϯ5.0 to 19.9Ϯ6.3 ng/mL).Gregorini et al 4 also reported that the combined use of aspirin and ticlopidine effectively inhibited platelet activation in patients who underwent angioplasty.In the ERASER study, all patients received aspirin before coronary intervention and ticlopidine use was left to the investigator's discretion.Therefore, we speculate that these combined therapies sufficiently inhibit platelet activation in the coronary circulation and that any additional effects of abciximab on platelets and, thus, in-stent restenosis were not observed in the ERASER study.
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Malik et al. (2000) conducted a letter in In-stent restenosis / Coronary stent implantation. Abciximab (on background of aspirin and ticlopidine) was evaluated on In-stent restenosis and coronary sinus platelet/coagulation activation markers (F1+2, TAT, beta-TG, PF4). Combined aspirin and ticlopidine prevented platelet activation (beta-TG 60.1 to 63.8 ng/mL; PF4 27.6 to 19.9 ng/mL) 24 hours post-stenting, explaining why abciximab did not reduce restenosis.
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