Pharmacoepidemiological approaches examining preventive medicines and multimorbidity in older people

Prescribing medicines for older people, aged 65 years and older, with multimorbidity is challenging. Preventive medicines are often prescribed in older people to prevent diseases or to confer health benefits. However, it is important to note that the prescribing of preventive medicines is guided by single disease guidelines that are often extrapolated from randomised controlled trials conducted in healthy adults. An insight to prescribing trends of preventive medicines at a population level is lacking. Real-world evidence of discontinuation of preventive medicines in the context of multimorbidity and life limiting illnesses is important in understanding the challenges of prescribing in this population. The overarching aim of this thesis was to employ pharmacoepidemiological approaches to examine the temporal trends in the utilisation of preventive medicines. The thesis also investigates the discontinuation of preventive medicines in older people in the presence of a recognisable life limiting illness or those with limited life expectancy. The secondary objective was to develop a Medicines Comorbidity Index (MCI) to quantify multimorbidity, a useful measure that should be considered for use in future pharmacoepidemiological research in New Zealand. The utilisation trends of preventive medicines are a reflection of the recommendations in current clinical guidelines. Over a 10-year study period, the utilisation of preventive medicines including aspirin, clopidogrel, dabigatran, statins and antihypertensive medicines increased. In contrast, a decrease for medicines such as dipyridamole, warfarin and bisphosphonates was noted. Interestingly, for centenarians, the utilisation trends of aspirin, clopidogrel, dipyridamole, statins and bisphosphonates declined over a 10-year period, however the utilisation of warfarin and dabigatran increased significantly over the same period. A systematic review on the discontinuation of preventive medicines for those approaching end-of-life found that the presence of limited life expectancy or a recognisable life limiting illness prompted the discontinuation of some preventive medicines, however the majority of individuals continued to take these medicines until death. Investigations of real-world data for older adults with cancer or dementia mirrored similar trends found in this systematic review. The seminal part of this thesis was the development of the MCI and its predictive performance was examined against the gold standard, the Charlson Comorbidity Index. A first of its kind for New Zealand, the MCI is a specific comorbidity tool that can be utilised in its full potential to screen for older individuals who are at an increased risk of adverse health outcomes. The benefits of simplifying multiple morbidities into a composite score is a useful variable to control for confounding in pharmacoepidemiological investigations. The MCI can be extended for use in other populations and it can easily be adapted to the population studied. In conclusion, the investigations carried out in this thesis provide an insight to the patterns of prescribing preventive medicines at a population level and generate strategies to improve the optimisation of preventive medicines use as end-of-life approaches. These investigations provide several pathways that can influence policy and facilitate decision making for health-care providers and stakeholders involved in improving the quality of prescribing in the geriatric population