Pharmacist interventions to improve medication adherence in patients with co-morbid hypertension and diabetes: a scoping review and bibliometric analysis

Abstract

Objectives

To evaluate the characteristics, assessment methods and overall impact of pharmacist-led interventions on medication adherence (MA) and clinical outcomes in patients with co-morbid hypertension and diabetes.

Methods

A predetermined search in four scientific databases (Scopus, Cochrane, Medline, and CINAHL) and a search engine (Google Scholar) was conducted between October 2023 and February 2024. This review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). A screening was conducted which considered the article type (original article), written in the English language and based on the study’s relevance while conference proceedings, reviews, and meta-analyses were excluded. Bibliometric indicators and VOSviewer were utilized to analyse and visualize keyword networks.

Key findings

Out of the 420 studies initially identified, 12 of them involving 3512 patients were analysed in this review. The majority (11) reported a significant effect of pharmacist interventions on MA to prescribe medications. Pharmacist-led interventions, including remote and in-person education, special monitoring, and medication simplification, significantly improved MA and clinical outcomes in patients with hypertension and diabetes. The inclusion of patient education in a pharmacist-led multimodal intervention achieved a 100% success rate in improving MA.

Conclusion

For patients with hypertension and diabetes co-morbidity, integrating pharmacist education in multifaceted interventions is more effective in improving MA and clinical outcomes.

Introduction

Hypertension and diabetes are significant risk factors for cardiovascular diseases (CVDs), the primary cause of death worldwide [1]. Co-morbidity is widespread, with estimates suggesting that over 40% of individuals with diabetes also suffer from hypertension [2, 3]. People with both illnesses are at a heightened risk of developing complications related to cardiovascular disease, highlighting the need for effective management techniques [1]including adhering to medication [2, 4]. Adherence not only affects physiological measures like blood pressure and glucose levels but significantly enhances a patient’s overall quality of life [4]. Patients who follow their drug regimens are more likely to have decreased symptoms and improved overall health outcomes [2]. Hypertension and diabetes have several interactions, necessitating a comprehensive and meticulous therapeutic approach [5, 6]. Patients with these disorders frequently take numerous drugs, which can make it even more difficult to adhere to their treatment regimen [7].

Pharmacists are essential in helping patients with both hypertension and diabetes to follow their medication regimen [8, 9]. As healthcare experts they evaluate medications, detect any adherence concerns and collaborate with patients to create strategies that will enhance adherence [10]. The effect of pharmacist-led interventions from previous studies in patients with either hypertension or diabetes had a positive impact [11, 12]. However, there is a gap in understanding the specific types and effectiveness of these interventions in patients with both conditions. Therefore, this review aimed to evaluate the characteristics, assessment methods, and overall impact of pharmacist-led interventions on MA and clinical outcomes in patients with co-morbid hypertension and diabetes. Additionally, a bibliometric analysis was conducted to identify and analyse trends in pharmacist interventions within this patient population, providing a comprehensive overview of the field.

Methods

This scoping review used the approach developed by Arksey and O’Malley, which was enhanced by Levac et al. [13] and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist [14, 15]. The review focused on pharmacist-led interventions targeted at improving MA and clinical outcomes in adults with both hypertension and diabetes and addressed the following research questions: (i) What defining features characterize pharmacist-led interventions in the studies? (ii) What methods were employed to evaluate the impact of these interventions on MA and clinical outcomes in patients with both hypertension and diabetes? and (iii) What were the general impact of these interventions on MA and clinical outcomes? These questions guided the study selection, the extraction of data, intervention summarization, techniques assessment, and their effects.

Eligibility criteria

To be included in the review, studies needed to meet several specific criteria. The population of interest was adults aged 18 years and older who had co-morbid hypertension and diabetes. Any pharmaceutical care intervention aimed at improving MA among the patients was considered. Outcomes of interest were MA rates and/or clinical outcomes related to hypertension and diabetes. The study designs included randomized controlled trials (RCTs), cohort studies, and quasi-experimental studies. Book chapters, meta-analysis studies, conference proceedings, and review articles were excluded to focus on original peer-reviewed research studies that provide direct empirical evidence.

Identification of studies

A systematic literature search was conducted from October 2023 to February 2024 to examine the effects of pharmacist interventions on MA. The search strategy included studies from all publication years to capture a comprehensive range of evidence, with no date restrictions applied. The search was conducted in Medline, SCOPUS, COCHRANE trials, CINAHL, and Google Scholar using specific predefined phrases to identify relevant studies. The search terms included ‘hypertension’, ‘diabetes’, ‘medication adherence’, ‘pharmacist’, ‘intervention’, and ‘pharmaceutical care’. The detailed search strategy is available in Supplementary Material S1.

Study selection

The review process followed a structured, three-stage approach. In the initial phase, the titles of all articles were screened independently by two reviewers (A.O.K. and I.A.K.) to assess their likely eligibility. The reviewers independently examined the abstracts of potentially relevant articles, eliminating those that clearly did not meet the inclusion criteria based on scope and objectives. For articles that passed the abstract screening stage, the reviewers retrieved and assessed the full texts independently. During this full-text review, each article was carefully evaluated against the inclusion criteria to confirm its relevance and suitability for the analysis. Disagreements on whether an article should be included in the review were settled through consensus.

Synthesis and charting the data

The process of data charting was carried out iteratively utilizing a study-specific extraction form that was associated with the research questions (Supplementary Material S2). Information was retrieved on research author(s), publication year, study design, country, study population, type of intervention (person and mode of delivery, intervention duration, and follow-up assessment time points), adherence measurement, and outcomes.

Medication adherence measures

MA was assessed using three distinct approaches across 12 studies: (i) digital medicine offering (DMO) technology (n = 1), which combines digital tracking with medication ingestion monitoring; (ii) self-reported assessments (n = 5), including validated tools such as the Medication Adherence Report Scale (MARS-10) and the Morisky Medication Adherence Scale (MMAS); and (iii) pharmacy-refill records (n = 6), which measure adherence based on prescription refills (Supplementary Material S3).

Quality assessment of included studies

The Joanna Briggs Institute (JBI) tools [16] were employed to critically appraise the randomized controlled trials, quasi-experimental studies, and cohort studies, as outlined in Table 1. Each field was categorized as ‘Yes’ (present), ‘No’ (absent), ‘Not Applicable’, or ‘Unclear’ (insufficient information). Two researchers (I.A.K. and A.O.K.) evaluated the studies independently using the JBI tool. All studies, regardless of their quality assessment scores, were included in the review to provide a comprehensive view of the available evidence.

Collating, summarizing, and reporting of results

The primary findings were reported following the study’s outcome measures and presented as types of pharmacists’ interventions, techniques for monitoring MA, and impact on patient’s adherence and clinical outcomes.

Bibliometric analysis

This study utilized the VOSviewer software version 1.6.20 for bibliometrics analysis because of its distinctive capability to visualize, investigate, and generate bibliometric maps [17]. Through the utilization of this programme, connections and associations between keywords were identified via co-word analysis. The VOSviewer enabled the identification of three primary clusters of keywords, as demonstrated in Fig. 2a. These clusters were automatically generated and colour-coded to highlight the relationships among terms within the analysed article. Furthermore, Fig. 2b displays the overlay visualization of the keywords. The keywords in the figure represent the trend of the years in which the co-occurring keywords were obtained. Keywords highlighted in purple were extracted from articles published before and including 2015, as per the legend. Green keywords are from publications published between 2015 and 2020, while yellow keywords are from articles published after 2020.

Results

Included studies characteristics

Out of the 420 studies initially identified, 12 studies involving 3512 participants were analysed in this review. Out of the 12 studies analysed, 8 [18–25]were RCTs, 2[26, 27] were retrospective cohort studies, and 2[28, 29] were quasi-experimental studies. Of the included studies, 8[19, 20, 22, 24–27, 29] were conducted in the USA, and 1 each in Ghana [23], Mexico [18], Brazil [21], and the Philippines [26]. The included studies demonstrated moderate to high methodological quality, with JBI scores from 54.5% to 92.3% and a median of 77.8%, reflecting overall robustness in study design.

From the year 2009 to 2024, there has been a rise in the number of studies involving patients with co-morbid hypertension and diabetes. The earlier research [19, 22] established a basis for investigating the involvement of pharmacists in managing multiple health conditions including hypertension and diabetes. The studies focused on pharmacist-led programmes, assessing their effectiveness in collaboration with physicians and other healthcare providers in clinical settings compared to standard care. In more recent publications, there was an emphasis on long-term pharmaceutical treatment programmes and telephone interventions, e.g. [24, 25, 27].

Visualization of mapping keywords

The first cluster, marked in red, contained 38 keywords. The most frequent keywords were ‘controlled study’, ‘human’, ‘male’, and ‘female’, all with equal connection strength. The keywords suggest a rigorous and well-structured study design, incorporating diverse demographic groups and controlled experimental frameworks to thoroughly evaluate the effectiveness of therapies. The green cluster, designated as the second cluster, included a total of 32 keywords. The predominant keyword was ‘medication compliance’, emphasizing the main goal of this study to enhance patients’ adherence to recommended medication regimens. Important terms like ‘diabetic patient’, ‘comorbidity’, ‘hypertensive patient’, and different antihypertensive and antidiabetic medications (e.g. ‘angiotensin receptor antagonist’, ‘dipeptidyl carboxypeptidase inhibitor’, ‘angiotensin-converting enzyme inhibitors’) emphasize the types of medications that were examined. The third and final cluster is represented by the colour blue. The most significant term was ‘major clinical study’. This may suggest a study characterized by a large sample size, a long duration, or significant findings.

An examination of trends in keywords indicated the current research emphasis on pharmacist interventions for patients with both hypertension and diabetes.

Medication adherence and clinical outcome measurements of pharmacists’ interventions

Eight studies included adherence measurements as the primary outcome [18, 19, 21, 24, 26–29], and 4 studies as a secondary outcome [20, 22, 23, 25]. Six studies [18, 24, 26–29] reported adherence measures without the evaluation of clinical outcomes while another 6 studies assessed clinical outcomes as either secondary (n = 2) [19, 21] or primary outcome measures (n = 4) [19, 20, 23, 25]. Three (3) studies [19, 23, 25] reported clinical results for both hypertension (systolic and diastolic) and diabetes (HbA1c and FBS), while three (3) studies [20–22] focused on hypertension outcomes.

Pharmacist intervention types

Counselling sessions: Contreras-Vergara et al. [18] implemented pharmacist-led educational sessions, which aimed to enhance patients’ understanding of medication management and their disease states. Similarly, Edelman et al. [19] utilized group medical clinics where pharmacists and internists collaborated to develop individualized care plans tailored to each patient’s needs. Geraldine Pablo et al. [26] also conducted educational seminars, providing patients with crucial information about managing their conditions and the importance of MA. Furthermore, Kwakye et al. [23] focused on education and counselling provided by clinical pharmacists, emphasizing the role of personalized education in improving adherence and disease management. A study by Neto et al. [21] offered a comprehensive pharmaceutical care program, addressing non-compliance issues through patient and family discussions, and various educational activities. Another study by Planas et al. [22] provided medication therapy management services, which aimed to optimize therapeutic outcomes for patients through structured medication reviews and consultations. In most of these studies, there were notable improvements in MA and clinical outcomes P < .05.

Telecommunication interventions: Three studies used telecommunication interventions to improve MA among non-adherent patients. In the study by Abughosh et al. [27], pharmacists conducted brief 3- to 5-min phone calls with 87 randomly selected patients on ACEI/ARB medication. A standardized template was used to identify barriers, provide education, and document issues, with telephone calls follow-ups sessions. After adjusting for all baseline covariates, the intervention emerged as a significant predictor of improved adherence in the linear regression model (β = 0.3182, 95% CI = 0.19–0.38, P < .001). In another study [25], pharmacy students conducted 6 motivational interviewing (MI) phone calls over 6 months with 250 non-adherent patients. Using the ask–provide–ask approach, barriers were identified and each interaction for review was documented before follow-up calls. Patients who completed the initial call along with a minimum of 2 follow-ups had a lower likelihood of discontinuation (OR = 0.29; 95% CI = 0.15–0.54; P < .001) and were more likely to be adherent in the linear regression model (β = 0.0604, P < .001).

Similarly, Stanton-Robinson et al. [29] had resident or student pharmacists use the DRAW (Drug Adherence Work-Up) tool [30] in telephonic interviews to identify barriers and recommend interventions. Patients were followed up within 3 days if needed and called up to 3 times. One month later, follow-up calls confirmed intervention implementation and updated prescription information. A significant increase in the total number of patients achieving adherence occurred at 90 days after baseline (P < .001) and at 180 days after baseline (P < .001).

Combined counselling and telecommunication interventions: Majd et al. [28] implemented a telephone motivational intervention, designed to enhance patients’ motivation, and adherence through regular phone interactions. Similarly, a study [24] used phone calls to deliver motivational support, encouraging patients to adhere to their medications and effectively manage their health conditions.

Frias et al. [20] introduced a digital medicine technology intervention, which supported patients in managing their medications and overall health through technological means. DMO was used to enhance MA based on an ingestible sensor, wearable patch, mobile app, and provider web portal. The ingestible sensor taken with medication, sent a signal to the patch, which also measured activity and vital signs. Data were transmitted to the cloud, allowing both patients and providers viewing access using a mobile app and a web portal, respectively. The app prompted medication intake, and investigators reviewed the DMO reports to guide treatment decisions. Participants were prescribed DMO for 4 or 12 weeks, with support available for troubleshooting. Medication adjustments were based on DMO data after initial use. By week 4, DMO participants with uncontrolled BP who maintained adherence (≥80%) were more likely than those receiving usual care to undergo antihypertensive dose titration aimed at achieving target BP. By week 12, the DMO group experienced a greater reduction in systolic blood pressure (SBP) compared to the usual care (mean –21.8, SE 1.5 mm Hg vs. mean –12.7, SE 2.8 mm Hg; mean difference –9.1, 95% CI –14.0 to –3.3 mm Hg).

Effect of pharmacists’ interventions on medication adherence and clinical results

Out of the twelve (12) studies, eleven (11) reported a significant improvement in MA (P < .05) [18, 20–29]. Incorporating patient education within pharmacist-led multimodal interventions resulted in a 100% success rate in enhancing MA.

One research [19] found no significant improvement in MA P = .53. Six studies [19–23, 25] focused on clinical outcomes. All studies demonstrated a notable improvement in clinical outcomes, such as decreased SBP, DBP, fasting plasma glucose levels, and HbA1c levels (P < .05). The only exception was the study by Edelman et al. [19], which did not show a significant change in HbA1c levels P = .159 but did indicate an improvement in blood pressure P = .011.

Discussion

The review identified pharmacist-led interventions and their effects on MA and clinical outcomes in patients with co-morbid hypertension and diabetes. Across the 12 studies that met the inclusion criteria, the interventions varied in approach, including counselling sessions, telecommunication interventions, and a digital medicine component. MA was assessed using 3 main methods: digital medicine offering panels, self-report assessments (such as the MARS-10 and MMAS), and pharmacy-refill records, which provided comprehensive measures of adherence. Overall, 11 studies reported significant improvements in adherence, and 6 studies demonstrated clinical benefits, such as lowered blood pressure and blood glucose levels, with only 1 study [18] showing no significant effect on adherence and HbA1c despite an improvement in blood pressure.

The studies included demonstrated moderate to high methodological quality (JBI scores ranging from 54.5% to 92.3%), supporting the reliability of findings and indicating robust study designs. The diversity of intervention types reflects adaptability, enhancing the relevance of pharmacist-led approaches across various patient populations. However, this review acknowledges some limitations. The analysis of the association between adherence and clinical outcomes could not be done since the majority of the studies either reported clinical outcomes as a secondary component of adherence or did not measure clinical outcomes at all. Another notable limitation is the absence of specific MeSH terms for pharmacist interventions, which underscores the need for further development in this area to enhance the precision of indexing and retrieval of relevant studies.

Research conducted in the past has shown that interventions led by pharmacists considerably enhance MA in populations of either hypertension or diabetes [31–33]. This study uniquely compiled interventions that pharmacists provided among patients with co-morbid hypertension and diabetes which was based on the impact of MA as well as clinical outcomes The review found that about 67% of the documents were by researchers based in the USA with the remaining from developing countries such as Ghana, Mexico, Brazil, and Philippines. Developed countries have more extensive research due to better funding, advanced healthcare systems, and higher awareness [34].

The bibliometric analysis offers critical insights. Early studies [19, 21, 22], foundational to current methodologies, established frameworks that underpin modern approaches in evaluating pharmacist intervention. Recent research [24, 28] indicates a shift towards more targeted, large-scale, and often multicentre studies, emphasizing the scalability of pharmacist interventions. The density visualization of keywords revealed a focus on controlled studies, gender differences between female and male participants, hypertension, diabetes mellitus, major clinical studies, aged populations, patient and medication compliance, randomized controlled trials, diabetic patients, and angiotensin-receptor blockers. It is important to note that no MeSH terminology is available for pharmacist interventions. This gap suggests the need for future development in this domain to promote exact indexing and retrieval of relevant studies [35, 36].

Approximately 92% of the studies reported interventions had a significant impact on the MA behaviour of patients. This suggests that while pharmacist interventions are generally effective, they need to be tailored to address individual-specific barriers such as health literacy, socio-economic status, access to healthcare resources, etc. which all play a role in how well patients adhere to their prescribed medication regimens [37].

The total success rate of pharmacist-led interventions targeted at improving MA was 100% for multimodal interventions that included patient education. This indicates that the active participation of pharmacists in multidimensional care models involving collaboration between other disciplines appears to be highly successful in promoting MA [31].

For most of the interventions, adherence was monitored with pharmacy-refill records including the proportion of days covered (PDC) which involves dividing the total number of days of supply over the course of the study by the number of days that were covered within 360 days following the index date [38]. The PDC method is useful for detecting patterns of non-adherence such as delayed refills or gaps in treatment which are crucial for managing chronic diseases [38]. The Morisky Medication Adherence Scale (MMAS) was another measure that was frequently utilized. This self-report measure was mostly used because of its ease of administration, simplicity, and low cost [39]. However, self-reporting methodologies tend to exaggerate the levels of adherence, which may potentially compromise the veracity of the claims that changes have been made [40].

While it was shown that interventions led by pharmacists regularly improved MA, it was not always the case that these interventions were associated with beneficial clinical results. This variance may be the result of differences in the types and designs of interventions, control groups, decisions on primary and secondary outcomes, and different assessment instruments for adherence [31]. Again, this review suggests that well-structured multicomponent interventions and regular follow-ups have a higher likelihood of being successful. Future investigations on the interventions of pharmacists should prioritize providing frequent patient contact. Furthermore, focus on patients who are most likely to benefit from these interventions, particularly those having difficulties adhering to their treatment regimen at the beginning. This will ensure that the available human and financial resources are utilized effectively.

Conclusion

Interventions led by pharmacists were associated with increased MA behaviour and improved clinical outcomes among patients with co-morbid hypertension and diabetes. While both remote and in-person interventions showed positive outcomes, the multifaceted interventions involving integrated pharmacist education were more effective in improving overall outcome measures. It is recommended that healthcare providers should prioritize multifaceted interventions that include integrated pharmacist education to maximize improvements in MA and clinical outcomes among patients with co-morbid hypertension and diabetes. Again, future studies should analyse how demographic variables impact the effectiveness of adherence interventions.

Supplementary Material

Supplementary data are available at International Journal of Pharmacy Practice online.

Conflict of interest statement: None declared.

References