Antithrombotic therapies in primary angioplasty: rationale, results and future directions

Despite the improvement in outcome observed with primary angioplasty compared with thrombolysis, there is still room for improvement. Indeed, despite restoration of optimal epicardial flow in the vast majority of patients, suboptimal myocardial reperfusion is observed in a relatively large proportion. The aim of this article is to provide an up-to-date review of adjunctive antithrombotic therapy for primary angioplasty for ST-segment elevation myocardial infarction (STEMI).The HORIZONS trial has shown a significant reduction in mortality and major bleeding complications in patients treated with bivalirudin compared with those treated with glycoprotein (GP) IIb-IIIa inhibitors. Thus, bivalirudin may be considered as an alternative strategy to heparin plus GPIIb-IIIa inhibitors in primary angioplasty, especially in patients at high risk for bleeding complications. However, despite the negative results of the FINESSE trial, a large amount of evidence has been observed in favour of early administration of GPIIb-IIIa inhibitors, which should still be considered a reasonable strategy.Non-responsiveness to aspirin and clopidogrel is relatively common. However, future trials are needed to evaluate whether the routine assessment for non-responsiveness and a consequent change in therapy (to higher dosages of clopidogrel or a switch to another adenosine diphosphate [ADP]-receptor antagonist) may improve clinical outcome. Even though not yet demonstrated, it is conceivable that the greatest benefits of clopidogrel may come from early administration, and that this might be considered as part of a pharmacological facilitation strategy, together with early administration of GPIIb-IIIa inhibitors. As a result of better and faster inhibition of platelet aggregation, further benefits might be expected from the early administration of one of the new oral platelet ADP-receptor antagonists.As a consequence of the very low mortality currently achieved by primary angioplasty, additional endpoints, such as infarct size and myocardial perfusion, should be considered when exploring the potential benefits of adjunctive antithrombotic therapies in future randomized trials among patients undergoing mechanical revascularization for STEMI.