Debate of adjunctive pharmacology for percutaneous coronary intervention: anticoagulation and clopidogrel are not (always) enough

Abstract

Substantial controversy exists regarding the optimal pharmacologic cocktail for percutaneous coronary intervention (PCI). The most common approach typically includes aspirin, clopidogrel, unfractionated heparin (or enoxaparin), and (variably) a glycoprotein (GP) IIb/IIIa inhibitor. Some substitute bivalirudin with "bail-out" GP IIb/IIIa blockade for heparin and planned GP IIb/IIIa integrin blockade, an approach that necessarily includes aspirin and clopidogrel (for their antiplatelet effects). These shifts in adjunctive treatment paradigms should be examined in the context of available data from clinical studies. Several studies have demonstrated the phenomenon of clopidogrel resistance to be fairly prevalent; even in clopidogrel-responsive patients, steady state is achieved only 4-6 hours after a 600-mg loading dose. It would thus be anticipated that clopidogrel-resistant patients would benefit from GP IIb/IIIa blockade, particularly during the period immediately after intervention. Neither REPLACE-2 nor the recent ACUITY trial demonstrated an efficacy advantage for bivalirudin as a substitute for heparin plus GP IIb/IIIa blockade; instead, any advantage appears to be limited to reducing the propensity for bleeding. As bleeding is directly correlated with the degree of anticoagulation and is further augmented by GP IIb/IIIa blockade, an alternative to the bivalirudin strategy is to simply reduce the amount of heparin anticoagulation during PCI. Finally, the benefit-to-risk ratio of aggressive adjunctive antiplatelet/antithrombotic therapy might be further improved via risk stratification, with patients at higher risk for periprocedural events receiving intensive therapy and lower-risk patients being managed with less intensive regimens focused on minimizing the risk of bleeding.