Optimising coronary reperfusion in acute myocardial infarction: the role of primary angioplasty

Abstract

Thrombolysis remains the predominant reperfusion strategy for ST segment elevation myocardial infarction (STEMI) in the United Kingdom. Although primary angioplasty may offer superior outcomes, the logistics of delivering this therapy in the UK have not been investigated. This thesis describes the development of a pilot primary angioplasty service in North East London. Outcomes are compared with the thrombolytic strategy, and platelet activation is explored as a possible biological mechanism determining reperfusion. The impact of the thrombolytic strategy on revascularisation following STEMI in North East London was first investigated. Thrombolytic delivery was effective, but necessitated frequent early revascularisation, leading to prolonged hospital stay. A primary angioplasty service was developed at the cardiac centre, and expanded to serve six network hospitals. Within the limitations of a daytime pilot, the service improved clinical outcomes, and was associated with a substantial reduction in hospital stay. Two admission strategies were compared - direct access to the cardiac centre following pre-hospital diagnosis by ambulance crews, and transfer of patients presenting to network emergency (A&E) departments after upstream administration of abciximab and clopidogrel. Direct access significantly reduced reperfusion times. Upstream anti-platelet therapy improved angiographic reperfusion prior to primary angioplasty, possibly compensating for inter hospital transfer delays. A subgroup of STEMI patients underwent platelet activation studies. Lower baseline platelet monocyte aggregate (PMA) levels predicted improved angiographic reperfusion following primary angioplasty, supporting the concept that PMAs may reflect plaque rupture severity, and may promote microvascular 2 dysfunction. Early anti-platelet therapy reduced PMAs following intervention, which may explain the benefit of early abciximab observed in clinical trials. In summary this thesis has demonstrated that primary angioplasty can be del ivered safely and eff ectively in North East London. The eff icacy of reperf usion may be determined by mechanisms involving platelet activation. Delivery of a 24 hour seven day service should now be addressed.