Cardiovascular disease is the leading cause of death worldwide and ischemic heart disease is the most common manifestation. Despite improved outcomes during the last decades, patients with acute coronary syndromes (ACS) are still at substantial risk of recurrent ischemic events and mortality. The aims of this thesis were to investigate the effect of the novel antiplatelet agent ticagrelor versus clopidogrel in patients with non-ST-elevation ACS (NSTE-ACS), overall and in relation to initial revascularization, and to explore this effect in relation to cardiac biomarkers. The impact of timing of revascularization in non-ST-elevation myocardial infarction (NSTEMI) was also studied, by assessing risk of mortality and recurrent myocardial infarction in relation to delay of percutaneous coronary intervention (PCI) in a nation-wide cohort. Finally, a novel clinical prediction model based on angiographic findings, biomarkers, and clinical characteristics was developed to estimate risk of ischemic events after performed revascularization. Ticagrelor treatment compared with clopidogrel was associated with a reduction in the composite endpoint of cardiovascular death/myocardial infarction/stroke and mortality alone, without any increase in overall major bleeding, but increased non-CABG-related major bleeding. The effect of ticagrelor over clopidogrel was consistent independent of initial revascularization. Elevated high-sensitivity cardiac troponin-T predicted benefit of ticagrelor over clopidogrel, while no difference between treatments was detected at normal levels. In patients with NSTEMI, PCI treatment within two days after hospital admission was associated with lower risk of all-cause death and recurrent myocardial infarction compared with delayed PCI. The new clinical prediction model included the following variables: prior vascular disease, extent of coronary artery disease, level of N-terminal pro-B-type natriuretic peptide and estimated glomerular filtration rate; and showed good discriminatory ability for the risk prediction of cardiovascular death/myocardial infarction/stroke and cardiovascular death alone. In conclusion, these results show that ticagrelor reduces the risk of recurrent ischemic events and mortality in patients with NSTE-ACS when compared with clopidogrel, and this effect seems independent of performed revascularization. The results also indicate that biomarkers could be used to select patients who would benefit most from more intense platelet inhibition. Furthermore, early PCI in NSTEMI seems to be associated with improved outcome. Finally, the novel clinical prediction model based only on four variables showed good discriminatory ability, which makes it a potentially effective and simple tool for tailored treatment based on individual risk of recurrent events.

Economic evaluations provide a tool to estimate costs and health consequences of competing medical technologies, ultimately to aid decision makers when deciding which medical technologies should be funded from available resources. Such decisions inevitably need to be taken under uncertainty and it is not clear how to approach them in health care decision-making. Recent work in economic evaluation has proposed an analytic framework where two related, but conceptually different decisions need to be considered: (1) should a medical technology be adopted given existing evidence; and (2) whether more evidence should be acquired to support the adoption decision in the future. The proposed analytic framework requires a decision-analytic model appropriately representing the clinical decision problem under consideration, a probabilistic analysis of this model in order to determine cost-effectiveness and characterise current decision uncertainty, and estimating the value of additional information from research to reduce decision uncertainty. The main aim of this thesis is to apply the analytic framework on three case studies concerning treatment strategies for cardiovascular disease in order to establish whether the treatment strategies should be adopted given current available information and if more information should be acquired to support the adoption decisions in the future. The implications for policy and methodology of utilising the analytic framework employed in the case studies are also discussed in this thesis. The results of the case studies show that a screening programme for abdominal aortic aneurysm in 65-year-old men is likely to be cost-effective in a Swedish setting and there appears to be little value in performing further research regarding this decision problem; an early interventional strategy in non-ST-elevation acute coronary syndrome is cost-effective for patients at intermediate to high risk of further cardiac events in a UK setting; endarterectomy in patients with an asymptomatic carotid artery stenosis is cost-effective for men around 73 years of age or younger in a Swedish setting and conducting further research regarding this decision problem is potentially worthwhile. Comparing the results of the present analyses with current clinical practice shows a need for changing clinical practice in Sweden regarding screening for abdominal aortic aneurysm and endarterectomy in patients with asymptomatic carotid artery stenosis. Furthermore, employing the analytic framework applied in the case studies can improve treatment guidelines and recommendations for further research. In particular, treatment guidelines ought to consider in which particular subgroups of patients an intervention is cost-effective. The case studies indicate that it is feasible to apply the analytic framework for economic evaluation of health care. Methodological development can improve the accuracy with which cost-effectiveness and value of information is estimated, but may also lead to comprehensive and complex evaluations. The nature of the decision problem should determine the level of comprehensiveness required for a particular evaluation.