Improving outcomes in patients with coronary heart disease using national registers and platelet function testing

University dissertation from Department of Cardiology, Clinical sciences, Lund University

Abstract: Introduction: Ischemic heart disease is the leading cause of death worldwide. The aims of this thesis were to evaluate different contemporary approaches in coronary care with regard to mortality and myocardial infarction. Methods: The thesis consists of 6 papers with 4 papers evaluating different exposures and their outcomes (clopidogrel pre-treatment, 5 different anti-platelet protocols, ticagrelor pre-treatment and treatment delays to PCI). Two papers involved evaluation of interventions: platelet function testing in patients with clopidogrel and clinical evaluation of bivalirudin versus heparin in patients with acute coronary syndromes, respectively. Patients with ischemic heart disease were identified using national and local registers. All patients in the six included papers were treated with PCI. Results: Pre-treatment with clopidogrel prior to primary PCI was associated with improved cardiovascular outcomes compared to peri-procedural clopidogrel. The composite end point of one-year mortality and MI was improved as well as mortality alone. Pre-treatement with ticagrelor compared to peri-procedural ticagrelor did not affect 30-day mortality. In one of three statistical models, 30-day myocardial infarction was reduced with ticagrelor pre-treatment. Platelet function testing failed to identify a clinically applicable cut-off value to predict stent thrombosis or new onset MI in patients with dual anti-platelet therapy. Using platelet function testing, a loading dose of either prasugrel or ticagrelor on top of a previous loading dose of clopidogrel, did not cause a pharmacodynamic overshoot of platelet inhibition. Treatment delays from first medical contact to PCI exceeding one hour were associated with higher mortality in patients with STEMI undergoing primary PCI. Finally, we showed that a register based randomized clinical trial designed to evaluate bivalirudin versus heparin in patients with ACS and PCI is feasible, with a higher degree of enrollment of “real-life” patients than in in conventional randomized clinical trials. Conclusions: This thesis has potential implications for acute care of patients with myocardial infarction.