Advances in cardiovascular pharmacogenetics and clinical outcomes in pharmacoepidemiology

This thesis aims to improve the current knowledge in pharmacoepidemiology and pharmacogenetics of cardiovascular medications in population-based settings and to provide more evidence on the safe prescription of these medications to enhance precision medicine. After the introduction in Chapter 1, Chapter 2 of this thesis focuses on the intersection of pharmacogenetics and cardiovascular outcomes, particularly the risk of SCD. By investigating the association between electrocardiogram measurements, genetic variants, and the risk of SCD, this research aims to enhance our understanding of medication-related cardiac risks and inform clinical decision-making in cardiovascular pharmacotherapy. In Chapter 2.1, we investigated the association between hydroxychloroquine and chloroquine use, changes in QTc-interval measurements and the risk of SCD. Chapter 2.2 assessed the relationship between a NOS1AP gene common variant (rs10494366 single nucleotide polymorphism) and the QT-interval shortening effect of digoxin use. Chapter 2.3 sought to establish the effect of the NOS1AP gene rs10494366 common variant on the risk of SCD in digoxin users in a population-based setting. Chapter 3 delves into the role of pharmacogenetics in guiding the use of cardiovascular medications, with a specific focus on genetic polymorphisms and their impact on drug responses. By evaluating the association between genetic variants in the CYP2C19 gene and the risk of all-cause mortality in clopidogrel users, Chapter 3.1 aims to elucidate the pharmacogenetic factors influencing medication efficacy and safety in cardiovascular disease management. Chapter 4 focuses on the pharmacoepidemiology of cardiovascular outcomes in individuals with T2D. Through systematic review and meta-analyses, Chapter 4.1 examines the impact of statins and novel pharmacotherapy approaches on cardiometabolic risk profiles. Chapter 4.2 reviews the effect of liraglutide on cardiometabolic risk profiles in people with coronary artery disease. Chapter 5 provides a comprehensive synthesis of the main findings and implications of the thesis. By integrating the insights gained from each chapter, this chapter offers a critical analysis of the current state of knowledge in pharmacoepidemiology and pharmacogenetics of cardiovascular medications. Moreover, it highlights future research directions and potential clinical applications, thus contributing to advancing precision medicine approaches in cardiovascular care.