Impact of Pharmacist-Led Interventions on Medication Adherence and Clinical Outcomes in Patients with Hypertension and Hyperlipidemia: A Scoping Review of Published Literature

Figures & data

Table 1 Inclusion Criteria

Category	Inclusion Criteria
Language of publication	English
Year of publication	2009–2019
Publication type	Original research articles
Outcomes measures	Medication Adherence and Clinical outcomes either as primary or secondary outcomes
Methodology	Studies assessing pharmacist’s interventions on outcome measures for hypertension and/or hyperlipidemia were eligible for inclusion
Pharmacist role	Pharmacists have to perform a leading role in designing and/or executing the interventions.
Patients	Adult patients aged 18 years old or above who were receiving cardiovascular medications.

Figure 1 PRISMA flowchart for selecting the studies according to the systematic scoping review methodology.

Table 2 Medicine Adherence Measurement Methods and Their Characteristics Reported in the Included Studies

Adherence Measurement Method	Self-Reported Adherence (MMAS and Its Related Scales) N=7	Refill Record-Based Adherence N=8	Prescription Abandonment N=1	Manual Pill Count N=1
Main Characteristics	Common in measuring adherence of antihypertensive drugs Simple and easy to be used Self-reporting style Subjected to overestimation of adherence level High chance of response bias	Common in measuring adherence of hyperlipidemia medications Common types: -Medication possession ratio (MPR) -The proportion of days covered (PDC) Quantitative measures Less subjected to overestimation of adherence level. Subjected to a possibility that medications being refilled – but not consumed properly.	Known as primary medication nonadherence Abandons to prescriptions portrayed that patients do not adhere to their medications Reasons for prescriptions abandon: low perceived benefit due to asymptomatic nature of the condition	More objective than self-reporting medication adherence Regarded as the gold standard for validating other methods It can be done without informing patients to avoid the disadvantage of pill dumping, where patients manipulate the number of pills.

Abbreviations: MMAS, Morisky Medication Adherence Scale; PDC, proportions of days covered; MPR, medication possession ratio.

Table 3 Studies Reporting Significant Improvement (P<0.05) in Medicine Adherence (N=11)

Author, Year, Country	Study Design and Population	Pharmacist Intervention	Comparator, Follow-Up and Outcome Measures	Key Findings
Ho et al, 2014^Citation23 (USA)	RCT involved 241 patients admitted with ACS and then discharged.	Multi-faceted intervention comprising medication reconciliation, patient education, collaborative care, and voice messaging.	Comparator: usual care. Follow-up: 12 months. Outcomes: Primary (refill adherence >0.8, % of adherent patients), Secondary (% of patients achieved BP and LDL-C targets).	The intervention increased adherence to statin (93.2 vs. 71.3%) (p=<0.001) and ACEI/ARB regimens (93.1% vs. 81.7%), (p=0.03) significantly. There was no significant changes in percentage of target BP or LDL-C levels attainments.
Lyons et al 2016^Citation27 (UK)	RCT involved 677 T2DM patients prescribed with LLT.	Two telephone-based Intervention, with medicine chart reminder.	Comparator: standard care. Follow-up: 6 months. Outcomes: Primary (self-reported nonadherence), Secondary (LDL-C levels).	The intervention group has less percentage of nonadherence compared to control group (10.6% vs. 19.6%, p=0.010). There was no associated significant difference in the clinical outcomes.
Taitel et al 2012^Citation16 (USA)	Retrospective cohort study included 2056 patients who were newly initiated on statin medications.	Two Face-to-face counselling session including a motivational interview	Comparator: control group. Follow-up: 12 months. Outcomes: medication adherence (MPR ≥80%).	The statin adherence has improved in the intervention group compared to control group is (61.8% vs. 56.9%, p<0.01). There was no assessment for clinical outcomes.
Choudhry et al, 2018^Citation22 (USA)	A Pragmatic cluster RCT involved 4078 patients’ non-adherent to their hypertension and hyperlipidemia medications.	Telephone-based behavioral interviewing, text messaging, and progress reports.	Comparator: usual care. Follow-up: 12 months. Outcomes: Primary (medication adherence, % of covered days), Secondary (LDL-C & SBP).	The intervention showed a significant improvement of 4.7% (95% CI, 3.0–6.4%) in medication adherence. There were no significant changes in the overall assessment of clinical outcomes.
Hedegaard et al, 2015^Citation21 (Denmark)	RCT included 532 patients prescribed with AHT and LLT.	Tailored medication review, patient interview, followed by telephone reminders.	Comparator: control group. Follow-up: 12 months. Outcomes: Primary (medication adherence, MPR ≥80%), Secondary (BP & hospital admission).	Nonadherence was higher in the control group (30.2% vs. 20.3%, p=0.01) as compared to the intervention group. There were no significant differences in the evaluated clinical outcomes.
Ramanath et al, 2012^Citation26 (India)	RCT involved 52 patients on AHT.	Counseling sessions using patient information leaflets and telephone reminders.	Comparator: control group. Follow-up: 1 month (twice). Outcomes: Primary (self-reported adherence, MMAS & MARS), Secondary (BP control).	The overall adherence increased significantly in the intervention group compared to the control group. There was no significant impact on BP control.
Morgadoet al 2011^Citation13 (Portugal)	RCT included 197 patients receiving AHT.	Counseling and educational sessions.	Comparator: usual care. Follow-up: 9 months. Outcomes: Primary (BP control), Secondary (self-reported medication adherence.	There was a statistically significant improvement in blood pressure control (66% vs. 41.7%, p = 0.0008) and medication adherence (74.5% vs. 57.6%, p = 0.012) between intervention and control groups.
Benbrahim et al 2013^Citation17 (Spain)	RCT included 176 patients on AHT.	Face-to-face (written and oral) tailored educational intervention.	Comparator: usual care. Follow-up: 6 months. Outcomes: medication adherence (pills count).	The adherence was increased significantly to 95.5% (baseline 86%) in the intervention group compared to 86.5% (baseline 85.4%) in the control group (p=0.011). There was no assessment for clinical outcomes.
Fischer et al, 2014^Citation18 (USA)	RCT included 124 131 patients with newly prescribed cardiovascular medications.	Live telephone calls with tailored educational messages	Comparator: control group. Follow-up: 30 days following index date. Outcomes: Primary medication adherence (prescription abandonment).	The live pharmacy-based interventions decreased primary medication adherence by 4.8% (P< 0.0001) compared to control group. There was no assessment for clinical outcomes.
Stewart et al, 2014^Citation24 (Australia)	Cluster RCT involved 395 patients who were taking at least one AHT.	Multi-faceted intervention consisted of motivational interviews, refill reminders, training on BP monitoring and medication reviews.	Comparator: control group. Follow-up: 6 months. Outcomes: Primary (self-reported adherence), Secondary (BP control)	No significant difference in % of adherent patients between control (57.2% vs. 63.6%) and intervention (60% vs. 73.5%) groups at baseline and 6 months, respectively. Non-adherence decreased from 61.8% at baseline to 39.2% at 6 months in the intervention group (P = 0.007). There was a significant SBP reduction in the intervention group (p=0.01).
Svarstad et al, 2013^Citation25 (USA)	Cluster RCT included 567 patients taking one or more AHT.	Team Education and Adherence Monitoring program involved tailored counselling and education using take-home toolkit, leaflets and medication box.	Comparator: control (only patient information). Follow-up: 6 and 12 months. Outcomes: adherence (refill ≥80%) and BP control.	Participants in the intervention group had better adherence (60% vs 34%, p<0.001) and BP control (50% vs. 36%, p=0.01) compared to the control group.

Abbreviations: ACS, acute coronary syndrome; RCT, randomized controlled trial; LLT, lipid-lowering therapy; SBP, systolic blood pressure; T2DM, type 2 diabetes mellitus; AHT, antihypertensive; LDL-C, low-density lipoprotein cholesterol.

Table 4 Studies with Non-Significant or No Improvement in Medicine Adherence (N=6)

Author, Year, Country	Study Design and Population	Pharmacist Intervention	Comparator, Follow-Up and Outcome Measures	Key Findings
Eussen et al, 2010^Citation29 (Netherlands)	A multicentre, open-label RCT included 899 patients on statin medications.	Five structured counselling sessions over a year.	Comparator: usual care. Follow-up: 6 and 12 months. Outcomes: Primary (adherence, 1-year discontinuation rate), Secondary (6 months discontinuation rate, ≥90% MPR and LDL-C levels).	The intervention showed a lower discontinuation rate of that was significant only at 6 months but not significant at 1 year. Median MPR was not significantly different between groups (99.5% vs. 99.2%, p=0.14). Adherent patients were more likely to achieve target LDL-c levels at 6 months (74% vs. 50%, p=0.01).
Kooy et al 2013^Citation19 (Netherlands)	RCT included 299 elderly patients (65 years or above) who had started statins at least one year.	Electronic reminder device (ERD) with or without counselling sessions.	Comparator: control group. Follow-up: 360 days. Outcomes: adherence (refill ≥80%).	Overall, refill adherence was not significantly improved with counselling with ERD (69.25, p=0.55), ERD only (72.4%, p=0.18) compared to control group (64.8%). There was no assessment for clinical outcomes.
Ma et al, 2010^Citation14 (USA)	RCT involved 689 patients with underlying CHD who had an LLT prescription.	Five Telephone counselling calls.	Comparator: usual care. Follow-up: 12 months. Outcomes: Primary (% patients achieved LDL-C levels), Secondary (adherence, continuous multiple-interval (CMA) from pharmacy records).	The intervention did not show significant improvement in statin adherence (0.88 vs. 0.90, p=0.51). It had no significant impact on clinical outcomes (65% vs. 60%, p=0.29).
Gums et al, 2015^Citation20 (USA)	Cluster RCT included 593 patients who had at least one AHT.	Physician-pharmacist collaboration management (PPCM)	Comparator: usual care. Follow-up: 9 months. Outcomes: Primary (Adherence, self-reported questionnaire), Secondary (medication changes).	There was no significant difference in the measures of medication adherence between the groups. Patients in the intervention group experienced higher medication changes compared to control group (4.9 vs. 1.1, p=0.003). There was no assessment for clinical outcomes.
Wong et al, 2013^Citation15 (Hong Kong)	RCT included 274 patients taking at least one long-term AHT and having suboptimal compliance	Counselling sessions with structured patient education and provision of pillboxes and medication knives.	Comparator: usual care (brief drug advice). Follow-up: 3 and 6 months. Outcomes: Primary (BP control), Secondary (adherence, self-reported)	Overall, both percentage of patients with optimal adherence and BP control were improved throughout study period. However, there were no significant differences between the groups in both outcome measures.
Van der Laan et al, 2018^Citation28 (Netherlands)	RCT included 170 patients who were on AHT.	Two face-to-face consultation (3 months apart).	Comparator: usual care. Follow-up: 9 months. Outcomes: Primary (self-reported adherence), Secondary (BP control).	There were no significant differences between intervention and control groups in both outcome measures.

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