Evidence for pharmacological interventions to reduce cardiovascular risk for patients with chronic kidney disease: a study protocol of an evidence map

Background: Patients with chronic kidney disease (CKD) require a personalised strategy for cardiovascular risk management (CVRM) to reduce their high risk of cardiovascular morbidity and mortality. Despite their high risk, patients with CKD appear to be underrepresented in randomised controlled trials (RCTs) for pharmacological CVRM interventions to reduce cardiovascular risk (pharmacological CVRM interventions). As a result, it remains unclear whether the efficacy of these interventions found in patients without CKD is similarly applicable to patients with CKD. This evidence map aims to provide an overview of the availability of the evidence from pharmacological CVRM trials for patients with CKD by assessing how often patients with reduced kidney function are specifically excluded or included from RCTs on pharmacological CVRM interventions and whether studies report efficacy estimates of interventions specifically for kidney patients. Methods: We will perform a systematic literature search in ClinicalTrials.gov to identify relevant planned, ongoing, and completed RCTs on a broad range of CVRM medications after which we will retrieve the published protocols and papers via ClinicalTrials.gov itself, Embase, MEDLINE, or Google Scholar. We will include RCTs that investigate the efficacy of platelet inhibitors, anticoagulants, antihypertensives, glucose-lowering medication, and lipid-lowering medication on all-cause mortality, cardiovascular mortality, cardiovascular morbidity, and end-stage kidney disease in patients with a cardiovascular history or a major risk factor for cardiovascular disease. Two reviewers will independently screen trial records and their corresponding full-text publications to determine eligibility and extract data. Outcomes of interest are the exclusion of patients with reduced kidney function from RCTs and whether the study population was restricted to kidney patients or subgroup analyses were performed on kidney function. Results will be visualised in an evidence map. Discussion: The availability of evidence on the efficacy and safety of pharmacological CVRM interventions in patients with CKD might be limited. Hence, we will identify knowledge gaps for future research. At the same time, the availability of evidence, or lack thereof, might warrant caution from healthcare decision-makers in making strong recommendations based on the extrapolation of results from studies to patients who were explicitly excluded from participation. Systematic review registration: PROSPERO CRD42022296746

Polypharmacy and Quality of Life Among Dialysis Patients: A Qualitative Study

Rationale & Objective: Almost all patients who receive dialysis experience polypharmacy, but little is known about their experiences with medication or perceptions toward it. In this qualitative study, we aimed to gain insight into dialysis patients’ experiences with polypharmacy, the ways they integrate their medication into their daily lives, and the ways it affects their quality of life. Study Design: Qualitative study using semistructured interviews. Setting & Participants: Patients who received dialysis from 2 Dutch university hospitals. Analytical Approach: Interviews were transcribed verbatim and analyzed independently by 2 researchers through thematic content analysis. Results: Overall, 28 individuals were interviewed (29% women, mean age 63 ± 16 years, median dialysis vintage 25.5 [interquartile range, 15-48] months, mean daily number of medications 10 ± 3). Important themes were as follows: (1) their own definition of what constitutes “medication,” (2) their perception of medication, (3) medication routines and their impact on daily (quality of) life, and (4) interactions with health care professionals and others regarding medication. Participants generally perceived medication as burdensome but less so than dialysis. Medication was accepted as an essential precondition for their health, although participants did not always notice these health benefits directly. Medication routines and other coping mechanisms helped participants reduce the perceived negative effects of medication. In fact, medication increased freedom for some participants. Participants generally had constructive relationships with their physicians when discussing their medication. Limitations: Results are context dependent and might therefore not apply directly to other contexts. Conclusions: Polypharmacy negatively affected dialysis patients’ quality of life, but these effects were overshadowed by the burden of dialysis. The patients’ realization that medication is important to their health and effective coping strategies mitigated the negative impact of polypharmacy on their quality of life. Physicians and patients should work together continuously to evaluate the impact of treatments on health and other aspects of patients’ daily lives. Plain-Language Summary: People receiving dialysis treatment are prescribed a large number of medications (polypharmacy). Polypharmacy is associated with a number of issues, including a lower health-related quality of life. In this study we interviewed patients who received dialysis treatment to understand how they experience polypharmacy in the context of their daily lives. Participants generally perceived medication as burdensome but less so than dialysis and accepted medication as an essential precondition for their health. Medication routines and other coping mechanisms helped participants mitigate the perceived negative effects of medication. In fact, medication led to increased freedom for some participants. Participants had generally constructive relationships with their physicians when discussing their medication but felt that physicians sometimes do not understand them

Supplementary Material for: Impact of Polypharmacy on Health-Related Quality of Life in Dialysis Patients

Introduction: Dialysis patients are often prescribed a large number of medications to improve metabolic control and manage coexisting comorbidities. However, some studies suggest that a large number of medications could also detrimentally affect patients’ health-related quality of life (HRQoL). Therefore, this study aims to provide insight in the association between the number of types of medications and HRQoL in dialysis patients. Methods: A multicentre cohort study was conducted among dialysis patients from Dutch dialysis centres 3 months after initiation of dialysis as part of the ongoing prospective DOMESTICO study. The number of types of medications, defined as the number of concomitantly prescribed types of drugs, was obtained from electronic patient records. Primary outcome was HRQoL measured with the Physical Component Summary (PCS) score and Mental Component Summary (MCS) score (range 0–100) of the Short Form 12. Secondary outcomes were number of symptoms (range 0–30) measured with the Dialysis Symptoms Index and self-rated health (range 0–100) measured with the EuroQol-5D-5L. Data were analysed using linear regression and adjusted for possible confounders, including comorbidity. Analyses for MCS and number of symptoms were performed after categorizing patients in tertiles according to their number of medications because assumptions of linearity were violated for these outcomes. Results: A total of 162 patients were included. Mean age of patients was 58 ± 17 years, 35% were female, and 80% underwent haemodialysis. The mean number of medications was 12.2 ± 4.5. Mean PCS and MCS were 36.6 ± 10.2 and 46.8 ± 10.0, respectively. The mean number of symptoms was 12.3 ± 6.9 and the mean self-rated health 60.1 ± 20.6. In adjusted analyses, PCS was 0.6 point lower for each additional medication (95% confidence interval [95% CI]: −0.9 to –0.2; p = 0.002). MCS was 4.9 point lower (95% CI: −8.8 to –1.0; p = 0.01) and 1.0 point lower (95% CI: −5.1–3.1; p = 0.63) for the highest and middle tertiles of medications, respectively, than for the lowest tertile. Patients in the highest tertile of medications reported 4.1 more symptoms than in the lowest tertile (95% CI: 1.5–6.6; p = 0.002), but no significant difference in the number of symptoms was observed between the middle and lowest tertiles. Self-rated health was 1.5 point lower for each medication (95% CI: −2.2 to –0.7; p < 0.001). Discussion/Conclusion: After adjustment for comorbidity and other confounders, a higher number of medications were associated with a lower PCS, MCS, and self-rated health in dialysis patients and with more symptoms