Pharmacist-led deprescribing of cardiovascular and diabetes medication within a clinical medication review: the LeMON study (Less Medicines in Older Patients in the Netherlands), a cluster randomized controlled trial

doi:10.21203/rs.3.rs-4995753/v1

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Research Article

Pharmacist-led deprescribing of cardiovascular and diabetes medication within a clinical medication review: the LeMON study (Less Medicines in Older Patients in the Netherlands), a cluster randomized controlled trial

https://doi.org/10.21203/rs.3.rs-4995753/v1

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Background

Deprescribing of inappropriate cardiovascular and diabetes medication has shown to be adequate, feasible and safe. Healthcare providers often experience the deprescribing of cardiovascular and diabetes medication as a challenge and therefore it is still not widely implemented in daily practice.

Aim

The aim was to assess whether a training on the performance of a more deprescribing-focused clinical medication review results in a greater reduction of inappropriate use of cardiovascular and diabetes medication.

Method

A cluster randomized controlled trial involving 20 community pharmacists, who conducted a clinical medication review in 10 patients. The intervention group received a training on deprescribing. Patients 70 years or older; polypharmacy and use of antihypertensive medication and having a systolic blood pressure below 140 mmHg, and/or use of diabetes medication and HbA1c level below 54 mmol/mol were included. Follow-up took place within four weeks (T1) and after three months (T2).

Results

71 and 69 patients were included in the intervention and control group, respectively. At T2 32% and 26% of the patients in the intervention and control group had the use of one or more cardiovascular or diabetes medication discontinued. With regard to any medication these percentages were 51% and 36%, respectively.

Conclusion

Increased awareness and ability of community pharmacists to deprescribe medication and use of general practitioners data, led community pharmacists and general practitioners to successfully conduct a more deprescribing-focused clinical medication review in daily practice. Further research on the need for additional training to optimize deprescribing cardiovascular and diabetes medication is required.

Deprescribing

Cardiovascular and diabetes medication

Frail older patients

Pharmacist-led intervention

Clinical medication review

The use of both CP medication records and GP clinical data in selecting older patients with polypharmacy for a clinical medication review allowed to better target patients potentially eligible for the deprescribing of antihypertensive and diabetes medication.
Although proposals to deprescribe medication were made for about 70-75% of the patients, the actual implementation rate of discontinuation is lower.
A deprescribing training of community pharmacists enhances the deprescribing of cardiovascular and diabetes medication in older patients with polypharmacy.
The increased awareness and ability of community pharmacists to deprescribe cardiovascular and diabetes medication contributed to a more deprescribing-focused clinical medication review in daily practice.

Polypharmacy is associated with medication-related hospital admissions [1]. Especially in older patients, polypharmacy can lead to an increased risk of drug related-problems. Due to age-related changes in pharmacodynamics and pharmacokinetics and increased frailty, potential harms can outweigh the clinical benefits of preventive medication over time. Preventive medication initiated in the past, can therefore become inappropriate, and its use may result in increased morbidity, hospitalizations and health care costs [1–5]. This indicates the need to evaluate prescriptions of preventive medication in older persons, especially frail ones. Deprescribing, defined as the process of withdrawing inappropriate medication, supervised by a healthcare provider (HCP) with the goal of managing polypharmacy and improving outcomes, [6], may be an important pharmacotherapeutic tool to counter inappropriate polypharmacy in frail older patients with multimorbidity, optimize their medication use, both in terms of outcomes and safety, and may improve their quality of life [7, 8]. Systematic deprescribing in primary care is usually part of a general practitioner (GP) or pharmacist-led multidisciplinary medication management process as a follow-up to a clinical medication review (CMR) [9]. Conducted at regular intervals, a multidisciplinary CMR is performed in primary care and nursing home care to manage polypharmacy in older patients with multimorbidity in order to prevent drug-related problems (DRPs) leading to falls, hospital admissions, a lower quality of life, increased mortality and excessive health care costs [10–24].

Although evidence is not unequivocal, deprescribing of inappropriate (preventive) cardiovascular and diabetes medication has shown to be adequate, feasible and safe [9, 25–33]. As the result, incentives for the deprescribing of this medication have been introduced in guidelines on the treatment of cardiovascular diseases and type 2 diabetes mellitus (T2DM) [26–29, 33–37]. HCPs, however, often experience the deprescribing of cardiovascular and diabetes medication as a challenge and therefore it is still not widely implemented in daily practice [9, 14, 38–42]. Barriers include a lack of evidence that discontinuation is more beneficial than continuation, HCP and patient uncertainty and fear of negative consequences, inadequate patient communication leading to unwillingness of patients or relatives, a lack of knowledge, time, training or support to allow HCPs routinely perform deprescribing and inadequate HCP collaboration [9, 13, 14, 38–45]. In the Netherlands community pharmacists (CPs) are responsible for offering adequate pharmacotherapeutic care and therefore have a significant role in medication management in primary care [11–13, 22, 23]. CPs have also been tasked to annually conduct CMRs in older patients with polypharmacy in collaboration with GPs, geriatricians, specialists geriatric medicine and other HCPs [12–14, 17, 19, 45–47]. Recommendations how to perform a patient-centered CMR, pharmacotherapeutic criteria and tools are provided by the Multidisciplinary Guideline ‘Polypharmacy in older patients’[45–47]. Despite its mandatory nature and remuneration, CMR implementation in practice is still not without problems, especially with regard to the deprescribing of (preventive) cardiovascular and diabetes medication [13, 14, 16, 17, 38, 39, 41, 45–48]. As a remedy, CMR eligibility has been restricted to high-risk patients and recommendations on deprescribing have been added [45, 47]. Criteria and considerations have now systematically been summarized in order to facilitate a patient-centered decision-making to continue, adjust or discontinue medication. However, to achieve full implementation of the MDRP in daily practice, the CPs, GPs and other HCPs involved need training and support, especially with regard to patient selection, decision-making and HCP collaboration/patient communication [8, 9, 12–14, 16, 41, 46–51].

Aim

The aim was to assess whether the completion of a training for CPs on how to conduct a more deprescribing-focused CMR, would result in a greater reduction in the (inappropriate) use of (preventive) cardiovascular and diabetes medication in terms of discontinuation, as compared to CMRs conducted without prior training.

Ethics approval

The study protocol was approved by Medical Ethics Committee of the VU University Medical Center in Amsterdam (2019.326). The study was registered at The Netherlands Trial Register (registration no: NL8082).

Study design and setting

The ‘Less Medicines in Older Patients in the Netherlands’ (LeMON) study, is a cluster randomized controlled trial conducted between November 2020 and December 2021. The study concerned an evaluation of the effect of a training for CPs aimed to conduct a more deprescribing-focused CMR with regard to cardiovascular and diabetes medication, in daily practice.

The BENU pharmacy chain provided a longlist of eligible CPs working in medium-sized and large pharmacies across the country. 35 CPs were invited to participate. 20 of these participated in the study and block-randomized in Castor EDC [52]. CPs randomized to the intervention group were asked to participate in (duration of about two hours) and apply the knowledge thus obtained in subsequent CMRs to be conducted jointly with GPs (N = 7–10) according to procedures outlined in the MDGP [47]. CPs randomized in the control group were asked only to conduct a similar number of CMRs. To minimize performance bias CPs in the control group were not informed about the content of the training.

CMRs and follow-up meetings with patients were in the pharmacies or completed electronically or by telephone, depending on the CPs’ own working procedures and CP and patient preferences. Outcomes were reported within four weeks after each CMR (T1) and after three months (T2). A flowchart of the study design is presented in figure one.

‘Insert Fig. 1 here’

Patient selection

Patients were selected by the CPs using data in the Pharmacy Information and Administration System (PIAS) and the General Practice Information and Administration System (GIAS). The inclusion criteria for patients were as follows: 70 years or older and chronic use of five or more drugs including at least one antihypertensive or antidiabetic drug (Anatomical Therapeutic Chemical [ATC] classification codes: A10: diabetes and C: cardiovascular system). In addition, patients should have a recently measured (< 6 months before inclusion) systolic blood pressure (SBP) < 140 mmHg and/or a HbA1c level < 54 mmol/mol. Life expectancy should be more than three months as estimated by the GP.

CPs selected eligible patients from their PIAS and contacted the GPs of these patients for collaboration and GIAS information on additional inclusion and exclusion criteria. In the case of linked systems (Pharmacom®-Medicom®) CPs had direct access to these data. CPs invited selected eligible patients by phone or at the pharmacies. They were subsequently informed about the study by their CP and were asked to provide informed consent before participation.

Sample size calculation

Based on previous studies it was assumed that in 40% of the patients the amount of cardiovascular and diabetes medication could be reduced [53]. With an α of 5% and power of 90%, 80 patients were needed in each arm. Considering a drop-out rate of around 10%, a total of 100 patients would have to be recruited per arm. To keep the workload per CP as low as possible, in view of the estimated number of patients fulfilling the inclusion criteria and a recruitment period of six months, conducting a CMR in 7–10 patients per CP was considered feasible.

Primary outcome measures

The primary outcome measure was the proportion of patients with one or more cardiovascular and diabetes medication deprescribed within three months after the CMR (T2).

Secondary outcome measures

Secondary outcome measures were the type of medication and number of proposed deprescribing interventions at the follow-up meetings with GPs and patients 1–4 weeks after the CMR (T1).

Data analysis

All analyses were done using Statistical Package for the Social Sciences version 15 software (SPSS). Descriptive statistics included the mean and standard deviation for normally distributed variables and median and interquartile range for nonparametric variables. Study groups were compared using χ2 or Fisher’s exact test for categorical variables and the Student’s t-test for normally distributed continuous variables. Following descriptive analysis, data were analysed with a logistic mixed model, which included a random effect model for CPs. Multilevel analysis was used to analyze the effect of clustering patients at the CP level. Age and sex were analysed as potential confounders. Adjustment was made for the number of medication at baseline level by including it as a fixed effect. For diabetes type 2 patients subgroup analyses was performed. All data were collected using Castor EDC and SPSS and discussed within the research team and with an expert in statistics. The CONSORT statement was used to evaluate the design and validity of this trial [54].

An overview of the inclusion of CPs is shown in Fig. 2. Between November 2020 and December 2021, 35 BENU pharmacies were invited, of which 19 indicated willingness to participate and were included. CPs were randomized to an intervention (N = 9) and control group (N = 10). One CP in the intervention withdrew after randomization (intervention) due to time constraints caused by unexpected staff shortages. The baseline characteristics of the participating CPs are shown in table 1.

‘Insert Fig. 2’

‘Insert Table 1 here’

The CPs included 140 patients: 71 in the intervention group and 69 in the control group, respectively. The baseline characteristics of these patients are shown in table 2.

‘Insert Table 2 here’

Table 3 shows the outcomes of the analysis for the intervention group as compared to the control group at T1 and T2, with adjustments for the covariates age, sex, blood pressure and amount of medication in the regression analysis.

‘Insert Table 3 here’

Of all patients that had signed an informed consent at T1, one or more proposals had been made for the deprescribing of cardiovascular and diabetes medication in 55% and 46% of the patients in the intervention group and the control group, respectively (table 3). With regard to all medicines, these percentages were 75% and 70%, respectively.

Three months after the CMR (T2) 32% and 26% of the patients in the intervention and control groups, respectively, had the use of one or more cardiovascular or diabetes medication discontinued. With regard to any medication these percentages were 51% and 36%, respectively. In the ‘antihypertensives’ medication group the number of deprescribed medicines was highest.

In the intervention group about two-thirds of the CP proposals to deprescribe resulted in the actual deprescribing of both all and cardiovascular or diabetes medication. In the control group this was the case in about half of the proposals that were implemented (table 3).

For intervention CPs on deprescribing, at T2 the odds of discontinuing cardiovascular or diabetes medication were 1.4 fold greater than for CPs who conducted a CMR in the usual manner. For all medicines, patients were 1.8 times more likely more to discontinue any medication at T2. The differences with regard to the deprescribing of cardiovascular and diabetes medication before and after correction for confounding variables in the regression models were not statistically significant (table 3).

Table 4 shows the nature and frequency of medication discontinued in the control and intervention groups. In total in the control and the intervention groups, 28 and 42 medicines were discontinued.

‘Insert Table 4 here’

The present study reports on the results of a cluster-randomized controlled trial investigating the effects of a deprescribing training for CPs on the deprescribing of cardiovascular and diabetes medication when conducting a CMR in older patients with polypharmacy. Although CPs who participated in the training on deprescribing were more successful in deprescribing (cardiovascular and diabetes) medication than CPs who conducted the CMR without additional training, this did not reach statistical significance.

In the present study, CPs made proposals to deprescribe any medication for 75% and 70% intervention and control patients. Proposals for the deprescribing of cardiovascular and diabetes medication were made for 55% and 46% of the patients. Following discussions with the GPs and patients, it appeared that after three months any medication had actually been deprescribed in respectively 51% and 36% and cardiovascular and diabetes medication in 32% and 26% of these patients. Ultimately, in the intervention group about two-third and in the control group about half of the proposals were actually implemented.

It is difficult to compare these results with those of other studies. This is mainly due to the different ways in which healthcare is organized in various countries and the specific roles of CPs and GPs in these systems [23], whether the CP or the GP is responsible for the CMR. In addition, the target groups of these studies also differ, such as for example, community dwelling patients and those living in a nursing home, patients of different age categories (older versus very old) and patients differing in health status, notably with respect to frailty and having a limited life expectancy.

In a Canadian CP-led intervention study in older community dwelling patients using medication with a high risk of inducing DRPs, oral diabetes medication was deprescribed in 30% of the patients using this medication for the duration of a six months follow-up period [18]. Regardless the medication used, in the Netherlands follow-up (3 months – 1 year) deprescribing rates in CP-led CMR intervention studies in older community dwelling patients ranged 20–50% with those for cardiovascular and diabetes medication falling within this range. In studies led by GPs but with CP assistance essentially similar results were obtained.

Reviews of both intervention and observational studies on the deprescribing of cardiovascular and diabetes medication in different categories of older patients show much wider ranges of deprescribing. For patients with diabetes medication with or without a cardiovascular condition rates between 13.4 and 75% were reported [28]. A similar wide range (27–94%) was reported in a review on the effects of various deprescribing approaches in older patients with a limited life span or living in nursing homes [33]. However, for community dwelling and nursing home patients with diabetes and low HbA1c levels oral diabetes medication deprescribing rates from 14 to 27% were found whereas for patients with diabetes and a low SBP the rates for this medication were between 16 and 19% [30]. A 66% three month deprescribing rate of antihypertensive medication was reported in an UK trial in primary care patients with hypertension aged 80 years or older [32].

The results of the present study are somewhat better than those of previous studies evaluating the extent to which conducting a CMR leads to the deprescribing of medication. The full implementation of the MDGP, making the annual CMR in frail older patients with polypharmacy a mandatory intervention, and the recent addition of guidance on deprescribing is likely to have increased the deprescribing rate over the years [47]. In the present study there is only a small difference between the deprescribing rate in the intervention group and the control group. Most likely this is due to the fact that in the last decade CPs have become increasingly aware of deprescribing, both as the result of experience gained in conducting increasing numbers of CMRs and the already wide attention given to deprescribing in Dutch medical and pharmaceutical journals and at local pharmacotherapeutic audit meetings. Moreover, current Dutch guidelines for the treatment of cardiovascular diseases and diabetes, which have been in use for several years now, offer a wide variety of options for the tailored treatment older patients [36, 37]. The deprescribing of medication in the majority of patients in the present study therefore appears to have been primarily mediated by an increased awareness and ability of CPs to deprescribe (cardiovascular and diabetes) medication.

Proposals for the discontinuation of medication are not always accepted by GPs and other prescribing HCPs, and patients. Proposals to discontinue or adjust medication were made for about 70–75% of the patients participating in this study. However, dependent on the type of medication to discontinued, the actual implementation rate of a CP-led CMR, however, is generally much lower [11, 13, 14, 17]. Although GPs and other HCPs generally recognize CP expertise, it is well known that there are several reasons that lead GPs and patients to reject CP proposals to discontinue medication [8, 9, 13, 14, 38–42].

Strengths and weaknesses

A strength of the present study is the use of both CP medication records and GP clinical data in selecting older patients with polypharmacy for a CMR. This allowed to better target patients potentially eligible for the deprescribing of cardiovascular and diabetes medication. Another strength is that deprescribing training and deprescribing-focused CMR were embedded in the current practice of conducting mandatory annual CMRs by CPs and GPs.

Unfortunately, the study was conducted during the COVID-19 pandemic. This affected CP inclusion and further study implementation as the result of which the study remained underpowered.

GP collaboration required to make CMRs is also increasingly difficult due to a shortage of GPs and the resulting lack of GP time [45]. This also means that there is an obvious need for clear criteria and responsibilities, as well as (electronic) tools that allow the efficient transfer of GP clinical information, facilitate the selection of patients and the obtaining of information from patients and ensure that CMRs including the deprescribing of medication, can be efficiently conducted [8, 9, 12, 19]. In the present study, most CPs had no direct access to blood pressure and HbA1c data. Conducting CMRs and the adjustment or deprescribing of (cardiovascular and diabetes) medication would be enhanced if PIAS and GIAS were (mandatory) linked so that this information,, is directly available to CPs.

Finally, a limitation could be that the effects of deprescribing were assessed only after three months, and that there are no longitudinal data.

A deprescribing training of CPs enhanced the deprescribing of (cardiovascular and diabetes) medication in older patients with polypharmacy selected on the basis of dispensing data and specific criteria for blood pressure level and HbA1c value. The increased awareness and ability of CPs to deprescribe (cardiovascular and diabetes) medication and use of GP data, led CPs and GPs to successfully conduct a more deprescribing-focused CMR in daily practice. A new study with a larger sample size is needed to demonstrate that a more deprescribing-focused CMR can be effectively conducted in daily practice. The need for additional training to optimize the deprescribing of (cardiovascular and diabetes) medication when conducting a CMR, and the methods and criteria to be used, require further development and study.

Conflicts of interest

The authors report no conflicts of interests. The authors alone are responsible for the content and writing of the paper.

Funding

The Royal Dutch Pharmacists Association (KNMP) provided a grant (2018 − 0387). They had no role in the study or in writing and publishing the article.

Author contributions:

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jamila Abou, Danielle Huijts and Jacqueline Hugtenburg. The first draft of the manuscript was written by Jamila Abou and Jacqueline Hugtenburg. Petra Elders, Rob van Marum and Danielle Huijts commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The research team would like to sincerely thank all the pharmacists for giving their time and expertise in a difficult period during COVID-19.

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29 Aug, 2024

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Pharmacist-led deprescribing of cardiovascular and diabetes medication within a clinical medication review: the LeMON study (Less Medicines in Older Patients in the Netherlands), a cluster randomized controlled trial

Status:

Version 1

Abstract

Figures

Impact statements

Introduction

Aim

Ethics approval

Methods

Study design and setting

Patient selection

Sample size calculation

Primary outcome measures

Secondary outcome measures

Data analysis

Results

Discussion

Strengths and weaknesses

Conclusion

Declarations

Conflicts of interest

Funding

Author contributions:

Acknowledgements

References

Tables

Supplementary Files

Status:

Version 1