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Development of a novel biomarker-based clinical prediction model for major adverse cardiovascular events in revascularized patients with acute coronary syndromes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
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(English)Manuscript (preprint) (Other academic)
Keyword [en]
acute coronary syndromes, risk prediction, biomarkers
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:uu:diva-265014OAI: oai:DiVA.org:uu-265014DiVA: diva2:862222
Available from: 2015-10-20 Created: 2015-10-20 Last updated: 2016-01-13
In thesis
1. Platelet Inhibition, Revascularization, and Risk Prediction in Non-ST-elevation Acute Coronary Syndromes
Open this publication in new window or tab >>Platelet Inhibition, Revascularization, and Risk Prediction in Non-ST-elevation Acute Coronary Syndromes
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 85 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1151
Keyword
coronary artery disease, myocardial infarction, acute coronary syndrome, non-ST-elevation acute coronary syndrome, P2Y12 inhibitors, ticagrelor, biomarkers, revascularization, percutaneous coronary intervention, risk prediction
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:uu:diva-265083 (URN)978-91-554-9384-4 (ISBN)
Public defence
2015-12-11, Enghoffsalen, Akademiska sjukhuset, ing. 50, Uppsala, 08:30 (English)
Opponent
Supervisors
Available from: 2015-11-17 Created: 2015-10-21 Last updated: 2016-10-07Bibliographically approved

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Lindholm, Daniel

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