Deprescribing in Dialysis: Operationalizing “Less is More” Through a Multimodal Deprescribing Intervention

“Less is more”, a quote attributed to Ludwig Mies van der Rohe, is now finding increased relevance across several fields, including medicine. Deprescribing is an exemplar of this proverb and describes the process of deliberately withdrawing medications, with the aim of reducing pill burden and improving health and quality of life.1Mohottige D. Manley H.J. Hall R.K. Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A Review.Kidney360. Sep 30 2021; 2: 1510-1522https://doi.org/10.34067/kid.0001942021Crossref PubMed Scopus (0) Google Scholar Deprescribing may mitigate multiple adverse events associated with polypharmacy including falls, cognitive disturbances, hospitalizations and mortality risk.2Reeve E. Gnjidic D. Long J. Hilmer S. A systematic review of the emerging definition of 'deprescribing' with network analysis: implications for future research and clinical practice.Br J Clin Pharmacol. Dec 2015; 80: 1254-1268https://doi.org/10.1111/bcp.12732Crossref PubMed Scopus (417) Google Scholar Polypharmacy is common among individuals with advanced kidney disease, with an estimated prevalence of nearly 86% among individuals with Stage 3b chronic kidney disease.3Schmidt I.M. Hübner S. Nadal J. et al.Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study.Clin Kidney J. Oct 2019; 12: 663-672https://doi.org/10.1093/ckj/sfz046Crossref PubMed Scopus (81) Google Scholar The potential harms of polypharmacy are also substantial, including higher mortality risk with ≥ 5 drugs [relative risk (RR) = 1.28, 95% CI 1.19-1.39] among adults over 65 years-old,4Li Y. Zhang X. Yang L. et al.Association between polypharmacy and mortality in the older adults: A systematic review and meta-analysis.Arch Gerontol Geriatr. May-Jun 2022; 100104630https://doi.org/10.1016/j.archger.2022.104630Crossref Scopus (25) Google Scholar and poorer health related quality of life among individuals receiving dialysis.5Colombijn J.M.T. Bonenkamp A.A. van Eck van der Sluijs A. et al.Impact of Polypharmacy on Health-Related Quality of Life in Dialysis Patients.American journal of nephrology. 2021; 52: 735-744https://doi.org/10.1159/000518454Crossref PubMed Scopus (9) Google Scholar Efforts to enhance judicious deprescribing in kidney care are urgently needed. These efforts must incorporate contextual factors unique to people living with kidney disease, including a rapidly evolving pharmaceutical armamentarium, dosing adjustments as eGFR declines, emerging multi-disciplinary kidney care models, and frequent health care engagement and associated cascading prescribing patterns.1Mohottige D. Manley H.J. Hall R.K. Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A Review.Kidney360. Sep 30 2021; 2: 1510-1522https://doi.org/10.34067/kid.0001942021Crossref PubMed Scopus (0) Google Scholar,6Naseralallah L. Khatib M. Al-Khulaifi A. Danjuma M. Prevalence and global trends of polypharmacy in patients with chronic kidney disease: A systematic review and meta-analysis.Front Pharmacol. 2023; 141122898https://doi.org/10.3389/fphar.2023.1122898Crossref PubMed Scopus (2) Google Scholar,7Beezer J. Al Hatrushi M. Husband A. Kurdi A. Forsyth P. Polypharmacy definition and prevalence in heart failure: a systematic review.Heart Fail Rev. Mar 2022; 27: 465-492https://doi.org/10.1007/s10741-021-10135-4Crossref PubMed Scopus (41) Google Scholar Addressing polypharmacy also requires clinical equipoise and shared-decision-making tailored to the medical complexity and substantial pill burden facing individuals with kidney disease.8Battistella M. Ng P. Addressing Polypharmacy in Outpatient Dialysis Units.Clin J Am Soc Nephrol. Dec 31 2020; 16: 144-146https://doi.org/10.2215/cjn.05270420Crossref PubMed Google Scholar A critical area of focus for de-prescribing interventions has been on potentially inappropriate medications (PIMs) – or medications that have been identified as having limited benefit and increased potential for adverse drug reactions (such as benzodiazepines and proton pump inhibitors PPI). Yet multiple barriers to PIM have been described, including clinician time constraints, fragmented medical records and unintegrated health IT systems9Sloan C.E. Zhong J. Mohottige D. et al.Fragmentation of care as a barrier to optimal ESKD management.Semin Dial. Oct 31 2020; https://doi.org/10.1111/sdi.12929Crossref PubMed Scopus (10) Google Scholar, poorly defined roles for deprescribing (e.g., nephrologist versus PCP), limited knowledge about PIMS among patients and clinicians, and symptom management priorities.10Hall R.K. Rutledge J. Lucas A. et al.Stakeholder Perspectives on Factors Related to Deprescribing Potentially Inappropriate Medications in Older Adults Receiving Dialysis.Clin J Am Soc Nephrol. Oct 1 2023; 18: 1310-1320https://doi.org/10.2215/cjn.0000000000000229Crossref PubMed Google Scholar Although studies have demonstrated that electronic clinical decision support for acutely hospitalized older adults may improve deprescribing in some specific contexts including inpatient settings11McDonald E.G. Wu P.E. Rashidi B. et al.The MedSafer Study: A Controlled Trial of an Electronic Decision Support Tool for Deprescribing in Acute Care.J Am Geriatr Soc. Sep 2019; 67: 1843-1850https://doi.org/10.1111/jgs.16040Crossref PubMed Scopus (39) Google Scholar, 12McDonald E.G. Wu P.E. Rashidi B. et al.The MedSafer Study-Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial.JAMA internal medicine. Mar 1 2022; 182: 265-273https://doi.org/10.1001/jamainternmed.2021.7429Crossref PubMed Scopus (40) Google Scholar, 13Moryousef J. Bortolussi-Courval É. Podymow T. Lee T.C. Trinh E. McDonald E.G. Deprescribing Opportunities for Hospitalized Patients With End-Stage Kidney Disease on Hemodialysis: A Secondary Analysis of the MedSafer Cluster Randomized Controlled Trial.Can J Kidney Health Dis. 2022; 920543581221098778https://doi.org/10.1177/20543581221098778Crossref PubMed Scopus (3) Google Scholar, less has been known about the efficacy of decision support tools on PIM deprescribing among individuals with kidney failure undergoing routine outpatient hemodialysis. In this issue of Kidney Medicine, Bortolussi-Courval et al. report their findings from a prospective, non-randomized controlled quality improvement study conducted across two dialysis centers in Montreal, Canada, conducted between September and December 2022, with one facility serving as the intervention site and the other as a control site. The authors compared the impact of Medsafer (n=68) versus traditional biannual medication reconciliation (n=127) on PIM deprescribing among outpatient dialysis patients who were prescribed a median of 4 PIMs on both the control and intervention units and >14 medications overall.14Bortolussi-Courval E, Podymow T, Battistella M, et al. Kidney Med 2024, in pressGoogle Scholar MedSafer is evidence-based, algorithm-driven intervention for effective deprescribing whereby patients’ electronic health record data is extracted and cross referenced against evidence-based guidelines to generate stratified reports listing PIMS based on their risk level (high, intermediate, and low) of developing an adverse drug event (ADE). Notably, in this study patients in the intervention group also received EMPOWER reports, which provided direct tailored feedback regarding select PIMS identified for deprescribing from their own medical record. The authors report that 40% of intervention unit patients achieved the primary outcome of having one or more PIMS de-prescribed (e.g., stopped, reduced, or versus 3% of control unit patients), corresponding to a 37% absolute increase in deprescription (number needed to treat = 3), with similar results in older as compared to younger patients. Of 45 total PIMS deprescribed, 89% were from patients from the intervention dialysis facility. Although ADEs were not assessed, authors report no deaths after medication reconciliation were related to deprescribing and did not identify adverse outcomes (such as a gastrointestinal bleed among individuals who had specific PIMS (such as PPIs) deprescribed. Notably, authors also report that 29% of deprescribing in the intervention unit resulted from newer clinical algorithm rules specified for dialysis that were incorporated into the Medsafer intervention, adapted from a prior dialysis-specific deprescribing guidelines developed by Lefebvre and colleagues15Lefebvre M.J. Ng P.C.K. Desjarlais A. et al.Development and Validation of Nine Deprescribing Algorithms for Patients on Hemodialysis to Decrease Polypharmacy.Can J Kidney Health Dis. 2020; 72054358120968674https://doi.org/10.1177/2054358120968674Crossref PubMed Scopus (10) Google Scholar, that leverage widely accepted PIM-guidelines including STOPP-STARRT and BEERS criteria.1Mohottige D. Manley H.J. Hall R.K. Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A Review.Kidney360. Sep 30 2021; 2: 1510-1522https://doi.org/10.34067/kid.0001942021Crossref PubMed Scopus (0) Google Scholar This is among the first studies to describe an effective multi-modal intervention deployed in outpatient dialysis units designed to enhance PIM deprescribing. Notably, Medsafer was initially tested by the same study group in a non-randomized study of 1066 hospitalized patients age ≥ 65 years that found an 8 % increase in deprescribing at the time of discharge (55% in the intervention group vs 47% in control)11McDonald E.G. Wu P.E. Rashidi B. et al.The MedSafer Study: A Controlled Trial of an Electronic Decision Support Tool for Deprescribing in Acute Care.J Am Geriatr Soc. Sep 2019; 67: 1843-1850https://doi.org/10.1111/jgs.16040Crossref PubMed Scopus (39) Google Scholar across several classes of deprescribed medications including antipsychotics, anti-diabetic drugs, PPIs, anticholinergic antihistamines, and sedative hypnotics. The Medsafer team subsequently conducted a cluster randomized controlled trial of 5,698 hospitalized patients age ≥ 65 years across 11 acute care hospitals in Canada, and noted an adjusted risk difference increase of 22% (95 CI: 17-27%) in deprescribing (55% in the intervention group vs 30 % in the control group).12McDonald E.G. Wu P.E. Rashidi B. et al.The MedSafer Study-Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial.JAMA internal medicine. Mar 1 2022; 182: 265-273https://doi.org/10.1001/jamainternmed.2021.7429Crossref PubMed Scopus (40) Google Scholar An exploratory post-hoc analysis done for that study focused on 70 hospitalized dialysis patients in each arm and noted a 9% increase in deprescribing with Medsafer (29 % among intervention group vs 19 % among the control group), demonstrating that the promise of the intervention described in this Kidney Medicine issue was possibly enhanced dialysis-specific algorithms.13Moryousef J. Bortolussi-Courval É. Podymow T. Lee T.C. Trinh E. McDonald E.G. Deprescribing Opportunities for Hospitalized Patients With End-Stage Kidney Disease on Hemodialysis: A Secondary Analysis of the MedSafer Cluster Randomized Controlled Trial.Can J Kidney Health Dis. 2022; 920543581221098778https://doi.org/10.1177/20543581221098778Crossref PubMed Scopus (3) Google Scholar The PRISM (Practical Robust Implementation and Sustainability model) framework accounts for the multi-level factors required for implementation success including diverse and variable user characteristics (e.g. patient and clinician characteristics), and the external environment (e.g. shifting clinical practice guidelines).16Nilsen P. Making sense of implementation theories, models, and frameworks.Implementation Science. 2020; 30: 53-79Crossref Google Scholar Bortolussi-Courval and colleagues provide multiple examples of how to enhance intervention success through careful implementation that addresses several PRISM elements. For instance, Medsafer’s success in this context may have been enhanced through the adaption a deployed evidence-based intervention,12McDonald E.G. Wu P.E. Rashidi B. et al.The MedSafer Study-Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial.JAMA internal medicine. Mar 1 2022; 182: 265-273https://doi.org/10.1001/jamainternmed.2021.7429Crossref PubMed Scopus (40) Google Scholar,17Moryousef J. Bortolussi-Courval É. Podymow T. Lee T.C. Trinh E. McDonald E.G. Deprescribing Opportunities for Hospitalized Patients With End-Stage Kidney Disease on Hemodialysis: A Secondary Analysis of the MedSafer Cluster Randomized Controlled Trial.Canadian Journal of Kidney Health and Disease. 2022/01/01 2022; 920543581221098778https://doi.org/10.1177/20543581221098778Crossref PubMed Scopus (3) Google Scholar which directly address barriers known to impact dialysis deprescribing (e.g., nephrologist time to collect and reconcile medications manually, EMPOWER brochures delivered to patients with accessible language regarding PIM risks and benefits). Provision of introductory emails regarding the intervention, as well as delivery of Medsafer deprescribing clinician report examples to intervention group nephrologists, may have also enhanced intervention uptake and perceptions of usability. Finally, Medsafer incorporates several components of a recently described decision-making framework, List Evaluate Shared Decision Making and Support (LESS)1Mohottige D. Manley H.J. Hall R.K. Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A Review.Kidney360. Sep 30 2021; 2: 1510-1522https://doi.org/10.34067/kid.0001942021Crossref PubMed Scopus (0) Google Scholar, by leveraging the electronic health record to create an accurate medication list, providing a clear review of medications for deprescribing with risk-stratified categories, and through delivery of patient-facing EMPOWER brochures which prompt patients to consider their need for specific PIMS and their associated risks. The study is notable for several strengths, including the presence of a control facility, elaborately described methodology to ensure internal validity, and non-crossover of nephrologists. The authors also assessed key process and implementation factors by conducting semi-structured interviews with nephrologists, which could aid development of future randomized clinical trials to test an adapted version of this intervention. In addition to deploying clinical algorithms to determine PIMs specific to individuals requiring dialysis, this intervention also engaged patients through provision of educational brochures describing select PIMs relevant to their care. However, several limitations of this study also deserve mention. This intervention is multi-modal and includes both patient-facing reports and clinician facing reports, making it challenging to quantify which component of the intervention arm (e.g., EMPOWER pamphlet distribution versus clinician reports) contributed to effective PIM deprescribing. Additionally, this study does not assess long-term intervention durability or patient outcomes and was not powered to impact ADEs. Future studies could examine long term outcomes including ADEs, hospitalizations, and patient-reported symptoms and outcomes associated with deprescribing, including medication complexity, which can be assessed through the Medication Regimen Complexity Index.1Mohottige D. Manley H.J. Hall R.K. Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A Review.Kidney360. Sep 30 2021; 2: 1510-1522https://doi.org/10.34067/kid.0001942021Crossref PubMed Scopus (0) Google Scholar Further information regarding operationalization of nephrology champions is also essential to understand the role of these individuals in intervention arm success. Finally, generalizability of these findings to settings lacking interoperable and unified electronic health systems (e.g., the United States) is also unclear and warrants further investigation in future studies.9Sloan C.E. Zhong J. Mohottige D. et al.Fragmentation of care as a barrier to optimal ESKD management.Semin Dial. Oct 31 2020; https://doi.org/10.1111/sdi.12929Crossref PubMed Scopus (10) Google Scholar,18Kelly Y.P. Kuperman G.J. Steele D.J.R. Mendu M.L. Interoperability and Patient Electronic Health Record Accessibility: Opportunities to Improve Care Delivery for Dialysis Patients.Am J Kidney Dis. Sep 2020; 76: 427-430https://doi.org/10.1053/j.ajkd.2019.11.001Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar Regardless, the authors present a compelling example of a multi-model intervention which directly addresses key barriers to dialysis prescribing. Over the past decade, multiple randomized controlled trials have tested interventions for deprescribing, including physician-pharmacist collaborative drug therapy management, mailing of educational brochure to patients and providers, and training sessions and family conferences for prescribers tailored for deprescribing.19Bayliss E.A. Shetterly S.M. Drace M.L. et al.Deprescribing Education vs Usual Care for Patients With Cognitive Impairment and Primary Care Clinicians: The OPTIMIZE Pragmatic Cluster Randomized Trial.JAMA internal medicine. May 1 2022; 182: 534-542https://doi.org/10.1001/jamainternmed.2022.0502Crossref PubMed Scopus (26) Google Scholar, 20Herrinton L.J. Lo K. Alavi M. et al.Effectiveness of Bundled Hyperpolypharmacy Deprescribing Compared With Usual Care Among Older Adults: A Randomized Clinical Trial.JAMA Netw Open. Jul 3 2023; 6e2322505https://doi.org/10.1001/jamanetworkopen.2023.22505Crossref PubMed Scopus (0) Google Scholar, 21Mortsiefer A. Löscher S. Pashutina Y. et al.Family Conferences to Facilitate Deprescribing in Older Outpatients With Frailty and With Polypharmacy: The COFRAIL Cluster Randomized Trial.JAMA Netw Open. Mar 1 2023; 6e234723https://doi.org/10.1001/jamanetworkopen.2023.4723Crossref PubMed Scopus (3) Google Scholar Although some of these approaches have successfully reduced pill counts, further studies are needed to explore the effectiveness of these interventions in kidney care settings and on long-term outcomes (e.g. hospitalizations, withdrawal events after deprescribing, ADE reduction, patient-reported outcomes). As robust electronic platforms for deprescribing support are further developed, attention should also remain on tools that support effective shared decision making and patient-centered communication. For instance, a novel electronic deprescribing tool “Mediquit,” which is in early stages of development in Germany,22Junius-Walker U. Viniol A. Michiels-Corsten M. Gerlach N. Donner-Banzhoff N. Schleef T. MediQuit, an Electronic Deprescribing Tool for Patients on Polypharmacy: Results of a Feasibility Study in German General Practice.Drugs Aging. Aug 2021; 38: 725-733https://doi.org/10.1007/s40266-021-00861-7Crossref PubMed Scopus (5) Google Scholar offers verbal prompts and phrases to aid deprescribing while providing tapering information and monitoring guidance for patients. Future tool development also ideally considers patients’ social contexts – or financial, physical, social, psychologic, and clinical factors that impede deprescribing (e.g., ability to pay, insurance status etc., patient health literacy). Finally, expansion of these electronic deprescribing tools to 1) identify opportunities for prospective medication management/deprescribing at multiple advancing stages of CKD, 2) robustly monitor (e.g., via telehealth) adverse drug withdrawal events and other outcomes, and 3) leverage pharmacist expertise warrants further consideration. Evidence regarding the multi-factorial benefits of PIM deprescribing is substantial. Findings from this study provide a compelling example of how deprescribing tools that utilize technology and evidence-driven algorithms coupled with patient-facing informational brochures may reduce deprescribing barriers (e.g., manual medication reconciliation, patient knowledge regarding PIM harms). As the US and other health systems strive to improve kidney care and patient outcomes through deprescribing, we must invest in promising solutions such as those presented by the Medsafer developers. By addressing foundational barriers that have impaired wider deprescribing success including dialysis care system fragmentation and EHR interoperability, we can move closer to this critical goal of enhancing kidney care delivery.18Kelly Y.P. Kuperman G.J. Steele D.J.R. Mendu M.L. Interoperability and Patient Electronic Health Record Accessibility: Opportunities to Improve Care Delivery for Dialysis Patients.Am J Kidney Dis. Sep 2020; 76: 427-430https://doi.org/10.1053/j.ajkd.2019.11.001Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar Support: DM is supported by the National Kidney Foundation Young Investigator Award; NHGRI Award under HG010248 and NIDDK Award under DK137259 Financial Disclosure: DM is a member of the NYC Coalition to End Racism in Clinical Algorithms, the ESRD National Coordinating Center Health Equity Taskforce, National Kidney Foundation Health Equity Advisory Committee, National Kidney Foundation Transplant Advisory Committee, and the NKF Greater NY Medical Advisory Board. Peer Review: Received January 11, 2023 in response to an invitation from the journal. Accepted February 16, 2024 after editorial review by the Editor-in-Chief.

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