CHAPTER 1 10 heart failure incidence and outcomes and assess the impact of eligibility criteria on the representativeness of heart failure trials. Aims of thesis The main aim of this thesis is to investigate generalizability of clinical trials for heart failure with reduced ejection fraction (HFrEF). The objectives of this thesis take three perspectives. First, we contrast patient characteristics and estimate generalizability of heart failure trials to observational registry cohorts. Because clear differences exist between trial and registry populations, we will include case-mix-adjusted outcome comparisons between study populations. In addition, we compare generalizability of these trials by outcomes in men and women. For the second objective, we assess at the design stage of trials, the impact of eligibility criteria of randomized trials on patient representativeness within European and Asian heart failure registries and subsequently in hypothetical trials by stepwise addition of the most commonly used criteria. Lastly, we focus on disentangling differences in incidence and heart failure outcomes by sex and ethnicity in a multi-ethnic community to highlight the importance of patient subgroup representation and diversity in future trials. OUTLINE OF THIS THESIS In the first part of this thesis (Chapter 2.1), we explore the differences between trial participants and registry cohorts and examined how risk factor adjustments affected the standardised mortality ratios between the populations. In Chapter 2.2 we identified the most frequently used inclusion and exclusion criteria for phase III HFrEF trials registered in ClinicalTrials.gov and subsequently compared eligibilities for the trials, based patient characteristics from an Asian and European registry cohort. In chapter three, we focus on demographic representation of trial populations. First, we determine whether all-cause and cardiovascular mortality outcomes for males and females in HFrEF trials differed from their counterparts in the registry cohort. In chapter 3.1 Next in chapter 3.2, we investigate the incidence of heart failure hospitalization and its 10- year trends by age, sex and ethnicity in a multiracial population in Malaysia. In chapter 3.3, we determine trends in prognosis of heart failure, in terms of readmission and mortality, differentiating between age, sex and ethnicity.
RkJQdWJsaXNoZXIy MjY0ODMw