Addressing Polypharmacy in Outpatient Dialysis Units

Research in the clinical practice of medicine is focused on how, when, and why caregivers should start new medications in patients. Although prescribing medications is appropriate for many clinical conditions, this may lead to polypharmacy. For instance, many patients have multiple conditions, including hypertension, diabetes, and cardiovascular disease, all of which require medications. Polypharmacy refers to the use of multiple concurrent medications, typically five or more per day (1). The term also describes the use of inappropriate medications, or more medications than clinically indicated (1). Therefore, it is surprising that there is a paucity of studies that address how and when these medications should be stopped. This paradox underlies the increasingly appreciated challenge of polypharmacy. We argue that there is a need to emphasize the new generation of data that demonstrate improved outcomes when a patient stops a medication to decrease polypharmacy.

Consequences of Polypharmacy

The consequences of polypharmacy include adverse drug reactions, drug–drug interactions, nonadherence, higher risk of cognitive impairment, impaired balance, falls, higher risk of morbidity, and hospitalization (1). Up to 10% of hospital admissions may be attributable to adverse drug events, with 30%–55% deemed preventable (1). The risk of an adverse drug event increases with the number of medications used, ranging from 6% for those using two medications, to 82% for those using seven or more medications (1). Finally, for people taking more than five medications per day, the risk of mortality is higher by 40% (2).

Because of the frequent presence of other comorbid chronic conditions (e.g., hypertension, diabetes, and cardiovascular disease) that require long-term medication management, individuals on hemodialysis (HD) have the highest number of medications of all chronically ill patient populations (3). In addition, patients on HD are rarely included in clinical trials, leading to uncertainty about the efficacy of many therapies in this patient population. Furthermore, these patients are prone to being trapped in “prescribing cascades” that exacerbate polypharmacy; this is when a drug is prescribed, an adverse drug event occurs that is misinterpreted as a new medical condition, and a subsequent drug is prescribed to treat this drug-induced adverse event (4). Finally, patients are at a greater danger of drug toxicity from medications that are not adequately removed by dialysis. All of this places these patients at higher risk of medication therapy problems and mortality related to polypharmacy (3).

Polypharmacy Is Common in Dialysis

Previous work assessing medication management and adherence in patients on HD found that patients were taking, on average, 12±5 distinct medications per day (about 19 pills daily), with 70% of these medications being potentially inappropriate (n=53). Because of numerous comorbidities, a typical patient on dialysis has four different prescribers and seven annual health care visits (3). This increases the risk of polypharmacy because of the potential for a lack of effective communication between prescribers (3).

Deprescribing May Help Decrease Polypharmacy and Its Risks

Deprescribing is one way to address polypharmacy and its consequences in patients on dialysis. This involves comprehensive medication management, determination of the patient’s goals of therapy, discussion of the risks and benefits of each therapy, and monitoring/follow-up for patient-reported clinical outcomes after any medication is withdrawn, tapered, or discontinued (5).

Existing studies on deprescribing have mainly focused on reducing inappropriate prescribing and polypharmacy in the elderly population (6). These studies demonstrate that the use of specific tools to guide deprescribing can effectively reduce polypharmacy in older adults (6). These interventions have also been associated with lower medication costs, fewer referrals to long-term care facilities (12% referrals in the intervention group versus 30% in the control) (6), lower mortality (21% intervention versus 45% control) (6), and improved perceptions of overall personal health (88% of patients reported global improvement in health) (6). Importantly, these were observed without an associated higher risk of long-term adverse outcomes (6). However, these tools were developed on the basis of safety and effectiveness data specific to the elderly population and, therefore, may not apply to other patient populations, such as patients on HD.

Although basic guides and generic algorithms for deprescribing exist, they have shortcomings. First, none of the existing tools include medication-specific deprescribing guidelines (6). As such, they lack practical suggestions on how to discontinue specific medications (e.g., tapering versus abrupt discontinuation) and do not recommend specific monitoring parameters when discontinuing medications. Second, these tools lack quantitative evidence on medication-specific benefits and harms. Finally, it is unclear if patient values and preferences contributed to these approaches (7). Patients report that their comfort with deprescribing necessitates the need to understand the appropriateness, safety, and requisite processes for the cessation of their medications (7). Patients want to be sure that their medications have benefits outweighing their risks, and that their medications are appropriate for their overall medical condition and goals of therapy (7).

Our group completed a single-center, prospective, observational study in which a deprescribing tool for five specific medications were developed, validated, implemented, and evaluated in a tertiary care center outpatient HD unit (8). In this pilot study, all 240 patients in the unit were screened using the deprescribing algorithms (8). The primary outcome was the proportion of target medications completely deprescribed after 4 weeks. Patient safety and satisfaction were monitored using medication-specific parameters outlined in their respective algorithms. We found that 71% (n=171) of patients were prescribed at least one of the five target medications. Of these patients, 23% (n=40) were identified as eligible for deprescribing; 88% (n=35) of them initiated a deprescribing protocol. At 4 weeks, 31 out of 40 (78%) target medications were deprescribed. Six months after the trial, only 16% of discontinued medications were represcribed, and 57% of patients were taking fewer medications than at baseline (9).

Although the pilot study was successful in many ways, there were also many lessons learned. To properly implement specific deprescribing algorithms in dialysis centers, both the patient and health care provider need to be in full agreement on the content and process of implementing the algorithms into practice. Therefore, the content of the algorithms and the implementation process should undergo consensus agreement and validation among all clinicians in the dialysis unit.

In addition, a number of patient barriers to deprescribing exist (8). In particular, patients can be apprehensive about deprescribing a medication when they do not sufficiently understand the deprescribing process or the target medication. Thus, patient perspective should factor into the design of our deprescribing tools for implementation. These algorithms should include steps to engage patients in discussions about the deprescribing rationale and available nonpharmacologic options. In each algorithm, patient involvement in the decision to deprescribe or restart medication should be emphasized.

There are different approaches to developing and validating deprescribing tools; however, there is no standard method for either stage. In the case of our own tool development, we gathered supporting literature, consulted clinical experts in kidney disease, and integrated this information. There is also no standard methodology for validation, but the Lynn method is commonly adopted for content validation (9). Our nine deprescribing algorithms have been validated over three rounds of review and revision by 45 nephrology experts from across Canada (nurse practitioners, nurses, clinical pharmacists, and nephrologists) using the Lynn method (9). Similarly, we developed and validated patient information tools (a bulletin and video) for each of the nine medications on a national scale, including one round of expert review and three rounds of patient review by 72 patients across Canada. We also developed evidence tables that summarize the available literature on safety and efficacy of each medication in patients on HD. Finally, we developed safety monitoring forms for each medication to assist clinicians in tracking the safety and effectiveness of initiated deprescribing attempts.

A Deprescribing Implementation Study

For deprescribing tools to be widely adopted and translated into meaningful outcomes, they should first be tested using an implementation science framework such as RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) (10). These frameworks allow for process measurement and the evaluation of feasibility of a deprescribing intervention. These frameworks also include evaluation of safety and effectiveness of interventions such as deprescribing. Furthermore, monitoring and evaluation of a program is vital to determine whether it is having the intended effect, to help refine delivery, and to provide evidence for continuing support. An implementation science framework would help to address barriers to a deprescribing intervention, such as how to incorporate these algorithms into electronic medication systems already in place at each institution, and how to effectively communicate and share this information between prescribing clinicians.

Deprescribing is a practical solution to polypharmacy observed in patients on dialysis. The development of deprescribing tools in dialysis must be unique to account for the characteristics of this population. Medication-specific algorithms assist the deprescribing initiative by outlining the decision-making process in a practical manner that is useful for all members of the care team, including nephrologists, nurses, pharmacists, dietitians, and social workers. In addition, patient-centered tools allow patients to understand and engage in the discussion to deprescribe, leading to greater acceptance and adoption of deprescribing plans. Together, the algorithms and patient tools are keys to an appropriately designed deprescribing intervention that can decrease medication costs, hospital admissions, and mortality, as well as achieve patient-centered goals and minimize the adverse consequences of polypharmacy.

Disclosures

All authors have nothing to disclose.

Funding

The authors' research is funded by Kidney Foundation of Canada grant KFOC170021 and Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR) grant: Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) grant CIHR SPOR SCA-145103.