Balancing safety and efficacy: recent clinical evidence optimizing outcomes in patients with intermediate to high-risk non-ST-segment elevated acute coronary syndrome

Significant developments have taken place over the past 15 years with respect to greater understanding of ischaemic risk in non-ST-segment elevation (NSTE) acute coronary syndrome (ACS) and respective management strategies. This includes recognition of the clinical benefit of an early invasive strategy and of the value of addressing various antiplatelet targets in the approach to pharmacotherapy. The guidelines focused on management of NSTE-ACS advocate the role of dual antiplatelet therapy with a recommendation for triple antiplatelet therapy, including a glycoprotein (GP) IIb/IIIa inhibitor (GPI), in patients who are determined to be at an elevated risk for ischaemic events. This may include those who are elderly, have a history of diabetes and/or renal impairment, and have elevated cardiac biomarkers (e.g. troponin) or ST-segment deviation at diagnosis. While triple antiplatelet therapy has demonstrated significant improvement in clinical outcomes in patients with NSTE-ACS, there is concern over the potential for an increase in haemorrhagic complications. Newer pharmacotherapies such as prasugrel and ticagrelor have demonstrated significantly greater efficacy as compared with clopidogrel in patients with NSTE-ACS deemed as high risk, although the incidence of certain bleeding complications was significantly increased with both of these agents. Additionally, efficacy has not yet been proved when compared with higher doses of clopidogrel, which has been shown to offer significant clinical benefits in patients who underwent percutaneous coronary intervention. Thus, a regimen of triple antiplatelet therapy including a GPI should remain a strong consideration for standard therapy in patients at high risk for ischaemic events, even in the prasugrel and ticagrelor era.