Appendices 212 On representation by population demography, we identified in chapter 3.1 that under-representation of females and older persons continue to occur in contemporary HFrEF trials. With available trial data, we found that the direction of trial-registry differences in heart disease-related deaths diverged between males and females; males in trials had 40% higher risk of death from heart-related conditions compared to their real-world counterparts. For females, there were no differences in heart disease-related mortality between trials and registry. This signals that factors beyond defined trial eligibility criteria, such as trial investigator and patient factors, influenced participation rates differentially between males and females. On a separate perspective of narrowing knowledge gaps in patient outcomes by demography, we presented data on 105 399 hospitalizations for heart failure from Malaysia in Chapter 3.2. Absolute number of first hospitalizations for heart failure rose by 52% from 2007 to 2016, driven by the population ageing particularly amongst those aged 60 years and above. This rise in numbers of older persons hospitalized for heart failure highlights a greater need to increase trial data for this subgroup than before. Nevertheless, it is reassuring to note that, when this rise in hospitalizations is subtracted from the expected trends in hospitalizations that is proportional to the growth of the older population, it translates instead to 1 % annual decline in first hospitalizations. This observation suggests that some expected cases have been prevented or delayed by existing measures in heart disease treatment. Chapter 3.3 further explores the disease progression of these heart failure hospitalizations in the form of repeat hospitalizations and death. We found that, though differences in treatment response in heart failure between race/ethnic groups are known, sparse reporting of race/ethnicity data in trials hampers generalizability evaluation by race/ethnic distributions except for selected countries such as the United States where both trial and observational cohort data were available. In this respect, we showed in the context of the Malaysian population, which is usually categorized as a homogenous racial group of Asians / Southeast Asians in trials, there exists distinct variation in re-hospitalization and death outcomes between ethnicities. Indian heart failure patients had 20% and 13% lower risk of 30-day and 1-year mortality compared to the majority ethnic group, Malays whereas Others, which mainly comprise Indigenous groups have a 30% higher risk of death within 30 days from hospital discharge. This underlines the value of
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