Immediate Pharmacology in the Current Era of Reperfusion Therapy

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Recent years have seen a resurgence in interest in the use of direct thrombin inhibition for the management of patients with ACS undergoing PCI. Early studies focused on the adjunctive role of recombinant hirudin and bivalirudin among patients undergoing fibrinolysis with no benefits in terms of mortality observed.14,15 While not evident with recombinant hirudin, bivalirudin, in the context of adjunctive therapy with streptokinase, was associated with a reduction in recurrent MI (HR 0.7, 95% CI 0.56-0.87, p=0.001) and modest increases in bleeding when compared with unfractionated heparin in the 17,073 patient study: Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial.14 Randomized trial evidence with primary PCI is currently confined to the Global Use of Strategies to Open Occluded Arteries (GUSTO) IIb angioplasty sub-study where patients undergoing primary PCI in the era before stenting are allocated to either hirudin or unfractionated heparin. Among the 503 patients in this study, a non-significant 23% reduction (p=0.37) in the 30-day incidence of death, recurrent MI or stroke, with no excess in bleeding, was observed.16 In the current era of coronary stenting, a randomized clinical trial with bivalirudin in primary PCI (HORIZONS) is on-going and contemporary evidence is limited to single-center registries suggesting the use of this agent is feasible.17

The key challenge to the clinician undertaking reperfusion is the integration of these data into effective clinical practice. Clearly impacting the choices is the form of reperfusion most commonly undertaken.

Within the context of fibrinolysis, intensifying antiplatelet therapy with clopidogrel in addition to aspirin provides incremental benefits in terms of recurrent MI and probably mortality and does not compromise safety if rescue PCI is required. Furthermore, more novel antithrombin approaches with enoxaparin, fondaparinux or bivalirudin are associated with some ischemic advantages, largely in recurrent MI, with less bleeding seen with fondaparinux. Whether enoxaparin and bivalirudin are more efficacious or safer options if rescue PCI is required may be postulated based on the observations seen in patients with non-ST-elevation ACS18-20 though direct supportive evidence for the concept is currently lacking. Among patients undergoing primary PCI, current evidence supports the use of abciximab started as early as possible, with the role of initial clopidogrel loading before PCI currently being undefined.

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