New “Anticoagulation”

Platelet-fibrin thrombus represents the essence of stent thrombosis.^1–8 Dual oral antiplatelet therapy (aspirin and thiopyridine) reduces significantly the risk of stent thrombosis after elective or urgent coronary stenting.^1–8 Intravenous platelet glycoprotein IIb/IIIa inhibitors also reduce the periprocedural thrombotic events after unplanned or elective stenting.^9–11 The results of REPLACE-2 found that bivaluridin with provisional use of glycoprotein GP IIb/IIIa inhibitor in 7% of the patients was superior to heparin for ischemic and bleeding complications and was non-inferior for ischemic complications but with less bleeding, less thrombocytopenia and shorter duration of treatment. This trial validates bivaluridin as an alternative foundation anticoagulant in percutaneous coronary intervention (PCI) with bare stent.¹² At 12 months, bivalirudin profides a significant reduction in mortality related essentially to bleeding.¹³ Sufficient evidence exists, therefore, to consider bivaluridin a choice “anticoagulant” for conventional PCI. Drug-eluting stents (DES) represent a major step in PCI, with a nearly complete correction of the restenosis process as was shown in a pivotal trial with sirolimus or paclitaxel.^14,15 Interestingly, there were no differences between bare and coated stents during the hospital phase, and even the first month following hospitalization, thus confirming the sole impact on restenosis. Controversial data emerged after the release of the Cypher stent in the U.S. which prompted the FDA and the manufacturer to issue a warning regarding the risk of subacute thrombosis (SAT). Neither pivotal trials (sirolimus or paclitaxel) showed any evidence of increased SAT and recent registries involving these two coated stents confirm the low incidence of SAT. These studies were conducted with heparin as the “anticoagulant” combined with clopidogrel. The interpretation of the SAT report showed that the problems were more mechanical in nature, with undersized stenting and/or uncovered dissection. Nevertheless, there are no data available yet regarding the safety and efficacy of bivaluridin use in drug-eluting stent implantation. In this paper by Medina and Foto, bivaluridin with provisional GP IIb/IIIa inhibition appears to represent an effective option for procedures involving the Cypher stent and other DES. Such a finding is in accord with previous studies comparing heparin and this antithrombin drug. Preliminary reports of the 1,180-patient ADEST registry involving Angiomax and drug-eluting stents in nine U.S. centers show a 30-day MACE rate of 5.5% (90% were CK elevation > 3), a mortality rate of 0.2%, acute stent thrombosis of 0.2%, and no incidence of subacute thrombosis.13 Confirmation of these data will install this antithrombin drug as the anticoagulation treatment of choice in PCI.