Patient safety : Cardio and cerebrovascular risk of major adverse events following exposure to potentially inappropriate medications

Abstract

Chapter 1 introduces what is known about the current challenges of medication management in the elderly, with a special focus on management of potentially inappropriate medications (PIMs) in clinical practice. Available evidence on PIMs with cardiac and cerebrovascular risk of adverse events, especially in terms of major outcomes (Major Adverse Cardiac and Cerebrovascular risk of Adverse Events – MACCE), is described. To answer to gaps in the knowledge identified during the literature review, a systematic review was conducted, described in Chapter 2.1, which showed that PIM‐lists focus mainly on common adverse events and often poorly describe the potential consequence for MACCE occurrence. To evaluate the extent of utilisation of such medications in older individuals, we conducted a prevalence study in ambulatory care and in longterm care facilities, described in Chapter 2.2, where we found that 59.4% patients were taking medications with Cardiac and Cerebrovascular Adverse Events (CCVAEs) risk, including 38.8% who used drugs with MACCE risk. Fifty percent of patients with a previous history of cardiovascular diseases were taking PIMs with risk of CCVAEs, including 30.0% with risk of MACCE. We also found a high proportion of patients using antipsychotics (APs), described as PIMs in the literature. In order to establish the mechanisms that may be linked to the occurrence of these events when using APs, we conducted a case/non-case study in a global pharmacovigilance database (Chapter 3.1). We found that APs with high affinity for Adrenergic alfa-1, Histaminic H1, Muscarinic M1, and Serotoninergic 5-HT2A receptors and with high-risk of metabolic side effects profile may explain the occurrence of those events. In Chapter 4.1 and 4.2, we have explored the knowledge of healthcare professionals (HCPs, including physicians, pharmacists, and nurses) on medication complexities among the elderly population, and the barriers experienced in managing these, particularly in managing PIMs. In this chapter, we also explored the patient-related features (PRFs) that should be considered when initiating treatment with APs in older individuals with dementia, and aspects to be focused during treatment monitoring. In Chapter 4.1, we found that most HCPs felt confident to manage medication complexities in elderly patients with dementia, but only a minority obtained a good score in the knowledge assessment test. The main barriers identified included structural barriers (tools unfit for practice) and process barriers (time), suggesting education per se will not necessarily lead to optimised pharmacotherapy in the elderly. Moreover, it seems that new tools, like clinical decision support systems (CDSS), are needed to facilitate the work of HCPs in daily practice, helping them to stratify the risk of adverse drug reactions (ADRs) when prescribing specific drugs. In Chapter 4.2, we found that, even though a high number of PRFs were rated as clinically relevant, some of them were identified as frequently missing from electronic medical records. Chapter 5 discusses all the results from the previous chapters. Overall, the conducted research shows person-centred tools are needed to consider the heterogeneity inside this population subgroup, as the ones available nowadays are more focused on the medication itself or even on different subgroups defined by comorbidities. Moreover, for such tools to be implemented in clinical practice, they need to be embedded into the software system and resort to data linkage, so that the full potential of electronic records is gauged. To consider a more tailored approach, a stratification risk calculator along within an electronic decision-making support would be of great interest to foster safe prescribing of medications in the elderly, particularly among those with dementia.