Bridging Knowledge Gaps in the Management of Acute Coronary Syndromes

Background Acute occlusion of an artery of the heart results in acute coronary syndromes (ACS), either with ST-segment elevation (STEMI) or without ST-segment elevation (1). STEMI requires urgent treatment to restore coronary artery flow either by primary percutaneous coronary intervention (PCI) or fibrinolytic therapy (FL) (2).  Although several randomized controlled trials (RCTs)  demonstrate the superiority of primary PCI in reducing mortality compared to FL (2), the benefit of primary PCI over FL remains uncertain in unselected “real-life” patients (3,4).  FL can be administered either in the pre-hospital setting (i.e., pre-hospital FL (PHL)) or at the hospital. PHL is rarely available outside Europe (5,6).  Insights into the organization of PHL systems of care may promote more widespread use of PHL. Risk stratification of ACS patients should be prompt to ensure timely PCI for high-risk patients and to avoid unnecessary intervention in low-risk patients (7).  Despite the availability of numerous ACS risk scores, there is still no simple risk score that can be easily applied in the initial management of ACS patients (8).  Objectives The objectives of this doctoral dissertation were to address these current knowledge gaps in the optimal management of ACS. The objectives were to: 1) evaluate the efficacy, effectiveness, and safety of primary PCI and FL, (2) describe the infrastructure, processes and outcomes of several international PHL systems; and (3) develop and validate a novel clinical risk score for early risk stratification of ACS patients.   Methods To address these objectives, I completed Bayesian hierarchical random-effects meta-analyses of published RCTs and observational studies which compare primary PCI and FL in patients with STEMI.  I undertook a survey of the infrastructure, processes and outcomes of PHL in several European and North American pre-hospital emergency systems.  Finally, I developed and validated an ACS risk score called the Canadian ACS (C-ACS). Results Primary PCI was superior to FL in reducing short-term mortality in RCTs and observational studies.  However, the long-term survival benefit of primary PCI was noted only in RCTs, and not in the observational studies. PHL can be effectively delivered by health care professionals with variable levels of expertise. The new risk score, C-ACS, has good discriminant properties for short- and long-term mortality in patients with ACS. Conclusions  The first manuscript of this dissertation has been recognized as one of the most valuable recent publications in STEMI management and has contributed to reorganization of STEMI care in Ontario.  The other two manuscripts in this dissertation provide practical information and tools for health professionals caring for patients with ACS.  In summary, this doctoral dissertation has and will continue to contribute to improve access to high quality care for patients with ACS.

Keyphrases: Meta-analyse, Myocardial infarction, Percutaneous coronary intervention, Risk score, Fibrinolytic therapy, Acute coronary syndromes, Reperfusion therapy, Pre-hospital medical services