The effect of down-titration and discontinuation of heart failure pharmacotherapy in older people: A systematic review and meta-analysis.

The aim of this study was to investigate whether interventions to discontinue or down-titrate heart failure (HF) pharmacotherapy are feasible and associated with risks in older people. A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to 8 March 2023. Randomized controlled trials (RCTs) and observational studies included people with HF, aged ≥50 years and who discontinued or down-titrated HF pharmacotherapy. Outcomes were feasibility (whether discontinuation or down-titration of HF pharmacotherapy was sustained at follow-up) and associated risks (mortality, hospitalization, adverse drug withdrawal effects [ADWE]). Random-effects meta-analysis was performed when heterogeneity was not substantial (Higgins I2 < 70%). Sub-analysis by frailty status was conducted. Six RCTs (536 participants) and 27 observational studies (810 499 participants) across six therapeutic classes were included, for 3-260 weeks follow-up. RCTs were conducted in patients presenting with stable chronic HF. Down-titrating a renin-angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% more likely than continuation (risk ratio [RR] 1.76, 95% confidence interval [CI] 1.14-2.73), with no difference in mortality (RR 0.64, 95% CI 0.30-1.64). Discontinuation of beta-blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95% CI 0.68-1.47). Participants were 25% more likely to re-initiate discontinued diuretics (RR 0.75, 95% CI 0.66-0.86). Digoxin discontinuation was associated with 5.5-fold risk of hospitalization compared to continuation. Worsening HF was the most common ADWE. One observational study measured frailty but did not report outcomes by frailty status. The appropriateness and associated risks of down-titrating or discontinuing HF pharmacotherapy in people aged ≥75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.

Supporting deprescribing in hospitalised patients: formative usability testing of a computerised decision support tool.

BACKGROUND: Despite growing evidence that deprescribing can improve clinical outcomes, quality of life and reduce the likelihood of adverse drug events, the practice is not widespread, particularly in hospital settings. Clinical risk assessment tools, like the Drug Burden Index (DBI), can help prioritise patients for medication review and prioritise medications to deprescribe, but are not integrated within routine care. The aim of this study was to conduct formative usability testing of a computerised decision support (CDS) tool, based on DBI, to identify modifications required to the tool prior to trialling in practice. METHODS: Our CDS tool comprised a DBI MPage in the electronic medical record (clinical workspace) that facilitated review of a patient's DBI and medication list, access to deprescribing resources, and the ability to deprescribe. Two rounds of scenario-based formative usability testing with think-aloud protocol were used. Seventeen end-users participated in the testing, including junior and senior doctors, and pharmacists. RESULTS: Participants expressed positive views about the DBI CDS tool but testing revealed a number of clear areas for improvement. These primarily related to terminology used (i.e. what is a DBI and how is it calculated?), and consistency of functionality and display. A key finding was that users wanted the CDS tool to look and function in a similar way to other decision support tools in the electronic medical record. Modifications were made to the CDS tool in response to user feedback. CONCLUSION: Usability testing proved extremely useful for identifying components of our CDS tool that were confusing, difficult to locate or to understand. We recommend usability testing be adopted prior to implementation of any digital health intervention. We hope our revised CDS tool equips clinicians with the knowledge and confidence to consider discontinuation of inappropriate medications in routine care of hospitalised patients. In the next phase of our project, we plan to pilot test the tool in practice to evaluate its uptake and effectiveness in supporting deprescribing in routine hospital care.

The Prevalence of Adverse Drug Reactions and Adverse Drug Events from Heart Failure Medications in Frail Older Adults: A Systematic Review.

INTRODUCTION: Frailty is highly prevalent in heart failure populations and a major risk factor for adverse drug reactions (ADRs) and adverse drug events (ADEs). This review aimed to describe the prevalence, causality and severity of ADRs or ADEs from heart failure medications among frail compared with non-frail older adults. METHODS: A systematic search of CENTRAL, MEDLINE, Embase, Ageline, CINAHL, International Pharmaceutical Abstracts, PsychInfo, Scopus, registries and citations prior to 18 May 2021 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. Risk of bias and quality of evidence were assessed. Eligible studies included randomised controlled trials (RCTs) and observational studies of people diagnosed with heart failure, aged ≥ 65 years, with frailty defined by an objective measurement, and reported ADRs/ADEs from/with heart failure medications. RESULTS: Two reviewers screened 2419 articles; interrater reliability kappa = 0.88. Three observational studies (n = 2596), a secondary analysis of two RCTs (n = 2098) and two cohort studies (n = 498) were included in a narrative synthesis. Frail patients in randomised trials of sacubitril/valsartan, aliskiren, or enalapril had twice the risk of mortality (hazard ratio [HR] 2.09, 1.62-2.71) and hospitalisations (HR 1.82, 1.37-2.41) compared with robust patients, which may reflect responsiveness to medications and/or factors unrelated to medication use. Hospitalisations from falls, tiredness and nausea were probably attributable to digoxin and possibly preventable according to the Naranjo and Hallas scales, respectively. CONCLUSION: The potential harms from heart failure medications in frail older people are poorly studied and understood. Clinical trials and pharmacovigilance studies should include frailty as a covariate to inform medication optimisation for this vulnerable and growing population. REGISTRATION: Prospero registration number: CRD 42021253762.

Stakeholder roles in facilitating access to essential medicines.

BACKGROUND: Persistent medicine shortages have highlighted that global access to essential medicines remain problematic. Existing supply chain vulnerabilities impact health systems and risk consumer safety. OBJECTIVES: This study aimed to examine how different key stakeholders' roles facilitate access to essential medicines. METHODS: In depth interviews were conducted with 47 participants across seven stakeholder groups globally. Stakeholders included government, academics, consumer groups, non-profit organizations, hospital healthcare providers, manufacturers, and wholesaler/distributors. An inductive approach to data analysis was undertaken. A pragmatic Grounded Theory "approach" was adopted, using tools such as open, axial, and selective coding. Thematic content analysis was applied to the comprehensive theory of collaboration to provide a contextual management framework to interpret themes. Results were displayed in Ishikawa fishbone diagrams for decision making and the logistics process. RESULTS: Findings showed that logistics management and therapeutic decision making were managed separately by stakeholders. Interestingly, hospital pharmacists had overlapping roles in patient care decisions and supply chain logistics, highlighting their importance as supply chain managers. Furthermore, despite the significant role that wholesalers/distributors had in managing supply disruptions and shortages, they were not involved in the decision-making process and did not participate in therapeutic selection committees. Additionally, sometimes stakeholders' intended control mechanisms contributed to increasing the complexity of the supply chain. CONCLUSION: There is a need for improved and innovative stakeholder engagement. Expanding the role of pharmacy to include hospital formulary pharmacists and including wholesaler/distributors in therapeutic selection committee decisions could improve these collaborations, may help to align the selection and procurement of medicines processes.

Stakeholder perspectives on the challenges surrounding management and supply of essential medicines.

Background Shortages of essential medicines impact patient safety and raise the costs of medicines to consumers and governments. Ongoing medicine shortages have become a critical issue that threaten global access to medicines. Objective The aim of this study was to explore key stakeholders' perspectives on the challenges surrounding management and supply of essential medicines. Setting Western Pacific, Asia, Europe, North America, and Africa. Methods In-depth, semi-structured interviews with 47 participants were conducted across seven stakeholder groups globally. Stakeholders included government, academics, consumer groups, non-profit organisations, hospital healthcare providers, manufacturers, and wholesaler/distributors. A grounded theory approach was applied to qualitative analysis. Main outcome measure Stakeholders' perspectives on the challenges surrounding management and supply of essential medicines. Results This study showed that supporting consumer demand for a wide range of therapeutic products required increased resources and coordination. Four main themes were identified: (1) consumer demand for a wide range of individual therapeutic needs cannot be sustained by the supply chain; (2) there lacked a coordinated approach to manage medicine shortages throughout the supply chain; (3) there were gaps in communication throughout the continuum of the supply chain; and (4) both international and local disruptions contributed to vulnerabilities in the supply chain. Conclusion Prioritisation of supply, logistics, and budget decisions around essential medicines need to be clearly coordinated between stakeholders to mitigate medicine shortages. Financial structures should include resilience planning to support fair and equitable access to medicines that meet consumer needs.