The effects of diuretic deprescribing in adult patients: A systematic review to inform an evidence-based diuretic deprescribing guideline.

In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research.

Discontinuation versus continuation of statins: A systematic review.

BACKGROUND: Clinicians and patients often face a decision to continue or discontinue statins. We examined the impact of discontinuation of statins compared with continuation on clinical outcomes (all-cause mortality, cardiovascular [CV] mortality, CV events, and quality of life). METHODS: We conducted a systematic review. Randomized controlled trials (RCTs), cohort studies, case-control studies, and quasi-randomized studies among people ≥18 years were eligible. We searched MEDLINE, Embase, and Cochrane Central Registry (inception to August 2023). Two independent reviewers performed screening and extracted data. Quality assessment was performed by one author and verified by another. We summarized results narratively, performed meta-analysis for a subset of studies, and used GRADE to assess certainty of evidence. We summarized findings in the subgroup of persons ≥75 years. RESULTS: We retrieved 8369 titles/abstracts; 37 reports from 36 studies were eligible. This comprised 35 non-randomized studies (n = 1,708,684) and 1 RCT (n = 381). The 1 RCT was conducted among persons with life expectancy <1 year and showed there is probably no difference in 60-day mortality (risk difference = 3.5%, 90% CI -3.5 to 10.5) for statin discontinuation compared with continuation. Non-randomized studies varied in terms of population and setting, but consistently suggested that statin discontinuation might be associated with a relative increased risk of mortality (hazard ratio (HR) 1.92, 95% CI 1.52 to 2.44, nine studies), CV mortality (HR 1.63, 95% CI 1.27 to 2.10, five reports), and CV events (HR 1.31, 95% CI 1.23 to 1.39, eight reports). Findings in people ≥75 years were consistent with main results. There was a high degree of uncertainty in findings from non-randomized studies due to methodological limitations. CONCLUSIONS: Statin discontinuation does not appear to affect short-term mortality near end-of-life based on one RCT. Outside of this population, findings from non-randomized studies consistently suggested statin discontinuation may be associated with worse outcomes, though this is uncertain.

Measuring Quality of Life in Deprescribing Trials: A Scoping Review.

BACKGROUND: Quality of life (QoL) is an important outcome to capture in clinical trials evaluating deprescribing interventions. OBJECTIVE: We aimed to conduct a scoping review to examine how QoL has been measured in deprescribing trials among older people and identify potentially relevant QoL scales, to better inform QoL measurement in future deprescribing trials. METHODS: We searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, Google Scholar, Epistemonikos, ClinicalTrials.gov, and reference lists of eligible studies (from inception to October 2023). We included randomized and non-randomized comparative studies with a control group that evaluated deprescribing and polypharmacy reduction interventions in people ≥ 65 years of age and measured QoL as an outcome. We also included studies describing the development and validation of QoL scales related to deprescribing, polypharmacy, or medication burden in adults ≥ 18 years of age. Two independent reviewers screened titles and abstracts, then full texts. Two independent reviewers extracted data from 25% of eligible studies in order to verify agreement, then a single reviewer extracted data from the remaining studies, which a second reviewer cross-checked. We critically appraised scales based on the COSMIN checklist. RESULTS: We retrieved 7290 articles, of which 52 were eligible for inclusion, including 44 deprescribing trials and eight scale development studies. From these studies, we found 21 scales that have been used in the context of deprescribing/polypharmacy (12 generic scales used in clinical trials and nine medication-specific scales). Variations of the generic EQ-5D were the most used scales. The measurement properties of scales for capturing changes in QoL from deprescribing were uncertain. Medication-specific QoL scales have not been employed in deprescribing clinical trials and thus, their performance in this context is also not clear. CONCLUSIONS: Several existing QoL scales have been applied to the context of deprescribing/polypharmacy clinical trials, and new scales specific to the problem have been proposed. If deprescribing does impact QoL, our findings suggest it is uncertain whether existing QoL scales can practically and reliably capture such a change or whether any scale is best. However, this review compares various aspects of the scales that researchers and clinicians can consider in decisions about measuring QoL in deprescribing trials, and in planning future research. PROTOCOL REGISTRATION: Open Science Framework: osf.io/aez6w.

What do clinical practice guidelines say about deprescribing? A scoping review.

INTRODUCTION: Deprescribing (medication dose reduction or cessation) is an integral component of appropriate prescribing. The extent to which deprescribing recommendations are included in clinical practice guidelines is unclear. This scoping review aimed to identify guidelines that contain deprescribing recommendations, qualitatively explore the content and format of deprescribing recommendations and estimate the proportion of guidelines that contain deprescribing recommendations. METHODS: Bibliographic databases and Google were searched for guidelines published in English from January 2012 to November 2022. Guideline registries were searched from January 2017 to February 2023. Two reviewers independently screened records from databases and Google for guidelines containing one or more deprescribing recommendations. A 10% sample of the guideline registries was screened to identify eligible guidelines and estimate the proportion of guidelines containing a deprescribing recommendation. Guideline and recommendation characteristics were extracted and language features of deprescribing recommendations including content, form, complexity and readability were examined using a conventional content analysis and the SHeLL Health Literacy Editor tool. RESULTS: 80 guidelines containing 316 deprescribing recommendations were included. Deprescribing recommendations had substantial variability in their format and terminology. Most guidelines contained recommendations regarding for who (75%, n=60), what (99%, n=89) and when or why (91%, n=73) to deprescribe, however, fewer guidelines (58%, n=46) contained detailed guidance on how to deprescribe. Approximately 29% of guidelines identified from the registries sample (n=14/49) contained one or more deprescribing recommendations. CONCLUSIONS: Deprescribing recommendations are increasingly being incorporated into guidelines, however, many guidelines do not contain clear and actionable recommendations on how to deprescribe which may limit effective implementation in clinical practice. A co-designed template or best practice guide, containing information on aspects of deprescribing recommendations that are essential or preferred by end-users should be developed and employed. TRIAL REGISTRATION NUMBER: osf.io/fbex4.

Reducing potentially inappropriate polypharmacy at a national and international level: the impact of deprescribing networks.

INTRODUCTION: Over the past decade, polypharmacy has increased dramatically. Measurable harms include falls, fractures, cognitive impairment, and death. The associated costs are massive and contribute substantially to low-value health care. Deprescribing is a promising solution, but there are barriers. Establishing a network to address polypharmacy can help overcome barriers by connecting individuals with an interest and expertise in deprescribing and can act as an important source of motivation and resources. AREAS COVERED: Over the past decade, several deprescribing networks were launched to help tackle polypharmacy, with evidence of individual and collective impact. A network approach has several advantages; it can spark interest, ideas and enthusiasm through information sharing, meetings and conversations with the public, providers, and other key stakeholders. In this special report, the details of how four deprescribing networks were established across the globe are detailed. EXPERT OPINION: Networks create links between people who lead existing and/or budding deprescribing practices and policy initiatives, can influence people with a shared passion for deprescribing, and facilitate sharing of intellectual capital and tools to take initiatives further and strengthen impact.This report should inspire others to establish their own deprescribing networks, a critical step in accelerating a global deprescribing movement.

Does LDL-C determination method affect statin prescribing for primary prevention? A register-based study in Southern Denmark.

AIMS: Examine whether low-density lipoprotein cholesterol (LDL-C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease. METHODS AND RESULTS: We conducted a register-based retrospective study in the Region of Southern Denmark. Two hospital-based laboratories in the Region directly measure LDL-C whereas four laboratories calculate LDL-C using Friedewald's formula. Physicians do not choose which method is used. We included all statin-naïve patients ≥40 years with no history of cardiovascular disease, diabetes, or chronic kidney disease, who had their LDL-C determined during 2018-2019. There were 202,807 people who had LDL-C determined during the study period (median age 59 years, 44% women) of which 37% had a direct LDL-C measurement. The median reported LDL-C was 3.40 mmol/L (IQR 2.90 to 4.00) for those with a direct measurement versus 3.00 mmol/L (IQR 2.40 to 3.50) for those with calculated LDL-C. For those with direct measurement, re-calculated LDL-C (using Friedewald's formula) was 0.35 mmol/L lower than the reported direct LDL-C measurement. Among those with directly measured LDL-C, 3.6% initiated statins compared with 2.7% of those with a calculated LDL-C. Direct LDL-C measurement led to higher odds of having a statin initiated compared to calculated LDL-C (adjusted odds ratio 1.23, 95% CI 1.17 to 1.30); for those with triglycerides > 1.7 mmol/L the adjusted odds ratio was 1.41 (95% CI 1.30 to 1.52). CONCLUSION: Differences in the reporting of LDL-C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins.

Prescribing Portraits to Optimize Prescribing of Proton Pump Inhibitors in Long-Term Care: PPI-T STOP Study.

Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications in Canada, particularly for older adults (at least 65 years of age). Overprescribing of long-term PPIs leads to health care system waste and is associated with adverse effects, including infections and fractures. The high prevalence of PPI prescribing in long-term care (LTC) facilities prompted an evaluation of systematic approaches to PPI deprescribing. Objective: To assess the impact of individualized prescribing portraits, a type of audit-and-feedback quality improvement intervention, on PPI deprescribing in the LTC setting. Methods: This prospective, nonblinded, uncontrolled, pre-post quality improvement study was conducted from December 2021 to April 2022 at a 126-bed LTC facility in Vancouver, British Columbia. A PPI prescribing portrait was developed for each prescriber (n = 5) at the LTC facility, containing the prescriber's personal PPI prescribing metrics as compared with those of their peers across all LTC facilities within the same health authority; an evidence summary for PPI deprescribing; and a personalized list of the prescriber's PPI-treated residents, along with their respective PPI indications and strategies for PPI deprescribing. Three months after the prescribers received their PPI prescribing portraits, the number and types of PPI deprescribing orders were recorded. Results: The implementation of prescribing portraits resulted in 17 (61%) of 28 PPI-treated residents receiving a deprescribing order by the end of the study period. Of the 28 PPI-treated residents, 20 were determined to be eligible for PPI deprescribing according to the evidence summary presented in the prescribing portrait; of these 20 residents, 16 (80%) appropriately received PPI deprescribing. Conclusions: Individualized prescribing portraits had the potential to increase evidence-based PPI deprescribing among LTC residents, beyond the extent of deprescribing previously achieved through standard of care.

Contexte: Les inhibiteurs de la pompe à protons (IPP) comptent parmi les médicaments les plus couramment prescrits au Canada, particulièrement chez les personnes âgées (au moins 65 ans). La prescription excessive d'IPP à long terme entraîne un gaspillage pour le système de santé et est associée à des effets indésirables, notamment des infections et des fractures. La prévalence élevée de la prescription d'IPP dans les établissements de soins de longue durée (SLD) a entraîné une évaluation des approches systématiques de déprescription des IPP. Objectif: Évaluer l'incidence des schémas de prescription individualisés, un type d'intervention d'amélioration de la qualité basée sur l'audit et la rétroaction, sur la déprescription des IPP dans les établissements de SLD. Méthodes: Cette étude prospective, sans insu et non contrôlée sur l'amélioration de la qualité pré-post a été menée entre décembre 2021 et avril 2022 dans un établissement de SLD de 126 lits à Vancouver, en Colombie-Britannique. Un schéma de prescription d'IPP a été élaboré pour chaque prescripteur (n = 5) de l'établissement de SLD, contenant les paramètres personnels de prescription d'IPP du prescripteur par rapport à ceux de ses pairs dans tous les établissements de SLD au sein de la même autorité sanitaire; un résumé des données probantes pour la déprescription des IPP; et une liste personnalisée des résidents du prescripteur traités par IPP, ainsi que, respectivement, leurs indications d'IPP pour la déprescription des IPP. Trois mois après la réception des schémas de prescription d'IPP des prescripteurs, le nombre et les types d'ordonnances de déprescription d'IPP ont été enregistrés. Résultats: La mise en œuvre de schémas de prescription a permis à 17 (61 %) des 28 résidents traités par IPP de recevoir une ordonnance de déprescription pendant la période d'étude. Sur les 28 résidents traités par IPP, 20 ont été jugés admissibles à la déprescription des IPP sur la base du résumé des données probantes présentées dans le schéma de prescription; sur ces 20 résidents, 16 (80 %) ont reçu de manière appropriée une déprescription d'IPP. Conclusions: Les schémas de prescription individualisés avaient le potentiel d'augmenter la déprescription d'IPP fondée sur des données probantes chez les résidents des établissements de SLD, au-delà de l'étendue de la déprescription précédemment atteinte grâce aux normes de soins.

Polypharmacy and Deprescribing in Older Adults.

Older adults commonly end up on many medications. Deprescribing is an important part of individualizing care for older adults. It is an opportunity to discuss treatment options and revisit medications that may not have been reassessed in many years. A large evidence base exists in the field, suggesting that deprescribing is feasible and safe, though questions remain about the potential clinical benefits. Deprescribing research faces a myriad of challenges, such as identifying and employing the optimal outcome measures. Further, there is uncertainty about which deprescribing approaches are likely to be most effective and in what contexts. Evidence on barriers and facilitators to deprescribing has underscored how deprescribing in routine clinical practice can be complex and challenging. Thus, finding practical, sustainable ways to implement deprescribing is a priority for future research in the field.

Development and validation of search filters to retrieve medication discontinuation articles in Medline and Embase.

BACKGROUND: Medication discontinuation studies explore the outcomes of stopping a medication compared to continuing it. Comprehensively identifying medication discontinuation articles in bibliographic databases remains challenging due to variability in terminology. OBJECTIVES: To develop and validate search filters to retrieve medication discontinuation articles in Medline and Embase. METHODS: We identified medication discontinuation articles in a convenience sample of systematic reviews. We used primary articles to create two reference sets for Medline and Embase, respectively. The reference sets were equally divided by randomization in development sets and validation sets. Terms relevant for discontinuation were identified by term frequency analysis in development sets and combined to develop two search filters that maximized relative recalls. The filters were validated against validation sets. Relative recalls were calculated with their 95% confidences intervals (95% CI). RESULTS: We included 316 articles for Medline and 407 articles for Embase, from 15 systematic reviews. The Medline optimized search filter combined 7 terms. The Embase optimized search filter combined 8 terms. The relative recalls were respectively 92% (95% CI: 87-96) and 91% (95% CI: 86-94). CONCLUSIONS: We developed two search filters for retrieving medication discontinuation articles in Medline and Embase. Further research is needed to estimate precision and specificity of the filters.

Impact of deintensifying hypoglycaemic drugs in older adults with type 2 diabetes: protocol for an emulation of a target trial.

INTRODUCTION: In older adults with type 2 diabetes (T2D), overtreatment with hypoglycaemic drugs (HDs: sulfonylureas, glinides and/or insulins) is frequent and associated with increased 1-year mortality. Deintensification of HD is thus a key issue, for which evidence is though limited. The primary objective of this study will be to estimate the effect of deintensifying HD on clinical outcomes (hospital admission or death) within 3 months in older adults (≥75 years) with T2D. METHODS: We will emulate with real-world data a target trial, within The Health Improvement Network cohort, a large-scale database of data collected from electronic medical records of 2000 general practitioners in France. From 1 January 2010 to 28 February 2019, we will include eligible patients ≥75 years who will have T2D, a stable dose of HDs, glycated haemoglobin A1c (HbA1c) value <75 mmol/mol (9.0%) and no deintensification in the past year. The target trial will be sequentially emulated (ie, eligibility assessed) every month in the database. Patients will be classified at baseline of each sequential trial in the intervention arm (deintensification of HDs: decrease of ≥50% in the total dose of HDs, including complete cessation) or control arm (no deintensification of HDs). The pooled dataset for all sequential emulated trials will be analysed. The primary outcome will be time to first occurrence of hospital admission or death, within 3 months. Secondary outcomes will be hospitalisation, death, appropriateness of glycaemic control and occurrence of HbA1c >75 mmol/mol within 1 year. Participants will be followed from baseline to 12 months after randomisation, administrative censoring, or death, whichever occurs first. A pooled logistic regression will be used to estimate the treatment effect on the incidence of the outcomes. DISSEMINATION AND ETHICS: No ethical approval is needed for using retrospectively this fully anonymised database. The results will be disseminated during conferences and through publications in scientific journals.

Recommendations on deprescribing of bisphosphonates in osteoporosis guidelines: a systematic review.

PURPOSE: Advancing age, declining health status, and a shift in benefit/risk balance warrant judicious use of preventive medications in older persons, including consideration of deprescribing. Lack of guidance on deprescribing is a major barrier for prescribers to consider deprescribing in daily practice. The aim of this review was to evaluate to what extent osteoporosis guidelines include bisphosphonate deprescribing recommendations. METHODOLOGY: We conducted a systematic review, searching PubMed, Embase, and grey literature. We included guidelines on treatment of osteoporosis with bisphosphonates. Two independent reviewers screened titles, abstracts, and full texts. Recommendations for deprescribing were extracted, and quality of guidelines were assessed. RESULTS: Among 9345 references, 42 guidelines were included. A total of 32 (76%) guidelines included deprescribing recommendations: 29 (69%) guidelines included non-specific deprescribing recommendations framed as a drug holiday, of which 2 (5%) also included specific deprescribing recommendations based on individual health context (e.g. life expectancy, frailty, function, preferences/goals). Twenty-four (57%) guidelines included practical deprescribing recommendations, and 27 (64%) guidelines included recommendations for when deprescribing should not be considered. CONCLUSION: Bisphosphonate deprescribing recommendations in osteoporosis guidelines were primarily framed as drug holidays, with limited guidance on how to make individualized deprescribing decisions based on individual health context. This suggests a need for additional focus on deprescribing in osteoporosis guidelines.

Revisiting systematic reviews on deprescribing trials to better inform future practice and research.

Deprescribing aims to address the problem of medication overuse in older adults. There has been an increasing number of systematic reviews of 'deprescribing'. We aimed to describe the categories of trials included in recent systematic reviews, and to make recommendations for future research. We categorized 122 trials included in eight recent deprescribing systematic reviews into: discontinuation, deprescribing implementation, medication optimisation (including medication initiation) and non-initiation trials. We identified heterogeneity and inconsistency in the categories of trials included in deprescribing systematic reviews. For example, 39 trials (32.0%) involved medication initiation in addition to the deprescribing component. It is now time for international researchers to develop and validate terminology used for trials involving discontinuation/deprescribing of medications, and to provide recommendations for evidence synthesis that will better inform future research, and translation into practice and policy.

Using Shared Decision-Making Resources in Long-Term Care: a Qualitative Study.

Background: Shared decision-making (SDM) incorporates people's individual preferences and context into individualized, person-centred decisions. Persons living in long-term care (LTC) should only take medications that are a good fit for them as individuals. Methods: We conducted a pilot study to understand experiences of two LTC homes in Ontario as they tested implementing SDM resources to support medication decisions. LTC homes conducted two Plan-Do-Study-Act (PDSA) cycles supported by an Advisory Group composed of LTC home representatives and stakeholders involved in resource design. Rapid qualitative analysis of transcripts and field notes from Advisory Group meetings elucidated how SDM resources were used. Results: Each site was positively engaged but implemented resources differently. The pharmacist and physicians at Site 1 introduced proton-pump inhibitor (PPI) deprescribing as their primary intervention, identifying suitable residents, informing residents and families of the deprescribing process, and providing selected SDM resources to residents, caregivers and staff. Representatives reported limited engagement with SDM resources and difficulty measuring the impact of PPI deprescribing. Representatives from Site 2 disseminated the SDM resources to residents and caregivers for use at care conferences and focused on front-line staff education and involvement. This site reported that some residents/caregivers were interested in participating in SDM and using the resources, while others were not. The impact of the resources on SDM at this site was unclear. Conclusions: Within the context of LTC, further research is needed to clarify the meaning and importance of SDM in medication decision-making. Implementation of SDM will likely require a multi-faceted approach.