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Abstract

Background:

Poor adherence to medications is a significant health care issue, particularly among cardiovascular patients. A variety of interventions have been tested by researchers in an effort to identify the most effective approach to improving adherence. Interventions delivered by multiple health care professionals (HCPs) may have an impact on improving adherence to medications in patients with chronic conditions, although the evidence to support this is still limited.

Objective:

To investigate the impact of interventions delivered by HCPs within a multiprofessional team to improve patients’ adherence to cardiovascular disease medications in community settings.

Search strategy:

The search strategy involved the use of the following data bases: Google scholar, PubMed, Medline, Cinahl, Embase, IPA, and Cochrane Library, from 1994 to 2010. Search was restricted to articles published in English.

Selection criteria:

Cluster randomized trials, controlled randomized clinical trials, prospective randomized trials, and nonrandomized studies were included. We considered any intervention designed to enhance adherence to medication directed by more than 1 HCP.

Results:

We included 17 studies testing 3 different types of interventions directed by more than 1 HCP. The HCPs received a variety of training via educational lectures or interactive workshops. Informational, behavioral, and combined interventions were delivered to cardiovascular patients. The majority of studies using only informational interventions or a combination of behavioral and informational interventions showed improvements in clinical outcomes (ie, blood pressure and total cholesterol lowering). However, only 2 studies measured improvements in adherence but the results were not significant. In contrast, all interventions based on the behavior change strategies improved both clinical outcomes and adherence to medication.

Conclusions:

Behavioral interventions delivered by a multiprofessional team appear to offer the best opportunity to improve clinical outcomes through improvements in adherence. However, whether interventions delivered by a multiprofessional team are more clinically effective than those delivered by a single HCP remain to be tested.

Keywords

adherence medications cardiovascular intervention health care professional multiprofessional teams

Introduction

Cardiovascular Disease

Cardiovascular disease (CVD) refers to “a group of disorders of the heart and blood vessels,” which include coronary heart disease, cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, and congenital heart disease.¹ The major modifiable risk factors for CVD are cigarette smoking, elevated blood pressure (BP), elevated serum total cholesterol (TC), low-density lipoprotein cholesterol, low serum high-density lipoprotein cholesterol (HDLc), obesity, and diabetes mellitus.² Continuous exposure to these risk factors leads to CVD progression, resulting in unstable atherosclerotic plaques, narrowing of blood vessels, and obstruction of blood flow to vital organs, such as the heart and the brain. The clinical manifestations of these problems are chronic angina pectoris, acute coronary insufficiency (unstable angina), recognized and unrecognized myocardial infarction, stroke, and CVD deaths.²

CVD is considered the most significant global health problem due to its high prevalence and mortality rates as well as the huge economic burden it imposes on individuals, communities, and health systems.³ CVD accounts for 30% of global deaths from all causes.² Approximately 3.7 million Australians are affected by CVD, and it is recognized as the leading cause of death.⁴ Although Australia has made impressive gains in reducing CVD morbidity and mortality, it remains Australia’s largest health problem especially among older people and people in lower socioeconomic groups.⁵

Management of CVD

Most CVDs can be well managed with treatment and in some cases may be reversed even after a long history of disease. Both primary and secondary preventions are highly effective in CVD management.² ^, ³ Primary prevention is mainly focused on controlling risk factors by encouraging smoking cessation, controlling high BP, reducing cholesterol levels, increasing physical activity, achieving a healthy weight, eating a healthy diet, and achieving full adherence to cardiovascular medicines.³ ^, ⁵ Secondary prevention involves the appropriate use of pharmacotherapeutic agents, including antihypertensives, lipid-lowering medications (eg, statins), antidiabetic, and antiplatelet agents, to prevent recurrent complications such as myocardial infarction and stroke in patients with established CVD.² ^, ⁵

Adherence to CVD Medications

Adherence may be defined as “the extent to which patients are taking medications as prescribed, following a diet, and/or executing lifestyle changes as recommended by health care providers,”⁶ while persistence is defined as the length of time that patients adhere to their medications.⁶ Adherence to medications plays a critical role in achieving better health outcomes (eg, improving symptoms and quality of life, slowing down disease progression, and reducing hospitalizations, morbidity, and mortality).⁷ Furthermore, studies have also demonstrated that poor adherence to medication in CVD is associated with increased hospitalization rates, poorer medical outcomes, and increased health care costs.^7,8

In the community, suboptimal adherence to long-term therapy for hypertension, dyslipidemia, and coronary heart disease is a continuing barrier to achieve therapeutic goals for patients with CVD (eg, achieving target BP and lipid levels).⁶ Poor adherence to cardiovascular medications has been reported to occur in more than 60% of patients with CVD, although self-reported adherence rates to cardiovascular medications differ depending on the medicines involved (Table 1).⁹

Table 1.

Rates of Adherence to Cardiovascular Medications

Medication	Self-reported Adherence,^a %^b
Aspirin	83
Lipid-lowering	63
β-Blocker	61
Aspirin + β-blocker	54
Aspirin + β-blocker + lipid-lowering	39

^aFollow-up survey.

^bProportion of patients reporting taking cardiovascular medication in 2002.⁹

Interventions Aimed at Improving Adherence to Cardiovascular Medications

Improving adherence to medication requires a range of strategies that primarily focus on fostering behavioral change. These strategies attempt to encourage the individual patient to learn, adopt, and sustain a regular pattern of medication-taking behavior.^8,10 A variety of interventions have been tested by researchers in an effort to identify the most effective approach in improving adherence to medications. These may be classified as informational interventions, behavioral interventions, or combined interventions (Table 2).¹¹

Table 2.

Types of Intervention

Types of Intervention¹¹	Examples^11,12
Informational	Education (individual education, intensive education, structured education, and group education), educational written materials, and/or booklet, flip charts, videotapes, patient logbooks, patient workbooks, educational newsletter sent via the post, self management plan, and routine counseling on medication and lifestyle changes (individual, home visit, or telephone counseling).
Behavioral	Special reminder packaging, tailored medication schedule, follow-up (telephone and/or home visits) by health care providers, simplification of dosing regimens, for example, use of once-daily instead of twice-daily dosage or using 2 medicines in 1 combined tablet, actual change of medication, electronic medication aid cap, for example, Medication Events Monitoring System, telephone-linked computer counseling, and direct observation of therapy by health care workers and family member.
Combined	Involved both informational and behavioral contents (eg, education program, reminders, counseling, and telephone follow-up).

The informational interventions (Table 2) focus on the provision of information and patient education. Both the content and intensity of such interventions vary considerably. They may involve provision of brief information in a single consultation through an intensive education lasting several hours over many sessions. These types of interventions involve health care professionals (HCPs) providing self-management plans, routine verbal counseling to patients on medications and lifestyle changes along with written educational material, and/or audiotape, logbooks, and patients’ workbooks. In contrast, behavioral interventions focus on simplification of dosing regimens, provision of reminders for prescription collection, enlisting support from family members to assist in adherence to medication, increasing patient motivation, telephone and/or visit follow-ups, as well as provision of continuous adherence monitoring with feedback support. Additionally, HCPs apply motivational interviewing techniques, which acknowledge the patients’ level of readiness to adopt healthy behaviors.¹¹ Combined interventions include both informational and behavioral components as well as social support strategies.^11,12 Recently, attention has focused on fostering opportunities for HCPs to collaborate on efforts to improve clinical outcomes in patients with chronic disease. A potential strategy in this regard is to develop models of collaborative practice among pharmacists, physicians, and nurses to support and increase adherence to medication and persistence in patients, especially those with chronic diseases.¹³ We conducted a review of the literature to assess the evidence for the effectiveness of multiprofessional health care teams delivering interventions targeting adherence to cardiovascular medications and to determine which types of interventions delivered within collaborative models were the most effective.

Objectives

The primary objective of this review was to investigate the impact of interventions targeted at improving patients’ adherence to cardiovascular medications in the primary care, outpatient, and community settings, delivered by HCPs within a multiprofessional team.

A secondary objective was to investigate how the HCPs were trained to deliver these collaborative interventions to patients with CVD.

Method

The search strategy involved the use of the following data bases: Google scholar, PubMed, Medline, Cinahl, Embase, IPA, and Cochrane Library. References were preferentially selected from 1994 to December 2010 as it was felt that relevant studies pertinent to the subject area would be found within this time period and would reflect the currency of the literature. The key words used in the search strategy were “adherence or compliance or persistence,” “medications or drugs or medicines,” and “cardiovascular diseases or hypertension or dyslipidemia or hyperlipidemia or chronic heart failure or chronic diseases,” “health care professionals or physicians and pharmacists,” “intervention or education,” and “collaboration or team-based care.” The search was restricted to articles published in English. The bibliographies of the retrieved articles were also searched for related articles.

Criteria for Considering Studies for this Review

Types of studies

Cluster randomized trials, controlled randomized clinical trials, prospective randomized trials, and nonrandomized studies were included.

Types of participants

We included HCP teams (including physicians and nurses or physicians and pharmacists or nurses and pharmacists), providing interventions for nonhospitalized patients with CVD in a primary care, outpatient (eg, ambulatory care provided by specialists/hospitals), or community setting (managed care organizations and general medical clinics).

Types of patients

We included adults with a diagnostic label of essential CVD in a primary care, outpatient, or other community setting.

Types of interventions

We considered any intervention that is designed to enhance adherence to medications, including the following: informational interventions (eg, counseling and health education), behavioral interventions (eg, simplification of dosage regimens), and combined interventions that were directed by at least 2 HCPs (eg, nurses, pharmacists, and physicians).

Control groups should have received either no intervention or “usual care” and have similar characteristics as the intervention group participants.

Types of outcome measures

We considered a study that measured adherence to medications (including any definition of adherence and noting how this was defined and measured in each study) and any other clinical outcomes, for example, BP or lipids, that is, TC and/or HDL.

Exclusion Criteria

Studies were excluded if interventions were not designed to increase adherence to medications and delivered by only one HCP. Hospitalized participants were also not considered in this review.

Results

The electronic search resulted in 305 citations, of which 54 appeared to fulfill the inclusion criteria. The full text of each article was reviewed, resulting in a total of 17 eligible articles that met the inclusion criteria, describing 16 studies (Table 3).

Table 3.

Characteristics of Reviewed Studies on Multi-HCP Interventions on Patients’ Outcomes and Adherence to Cardiovascular Medications

Study	Design	Setting, Patients’ no. (I/C)	Study Duration	Types of Intervention	Intervention Delivered by^a	HCPs Training	Control Group	Described Measures	Adherence Measures	Results	Comments
Dyslipidemia and Atherosclerosis
Bogden et al, USA¹⁴	A single-blind RCT	Community (47/47)	6 Months	Informational (Pharmacist reviewed patients’ medication history and laboratory data, encouraged patient adherence, determined least costly regimen, and recommended changes in medications; Physicians assessed secondary causes of hyperlipidemia, reviewed laboratory data, and managed risk factors and comorbid conditions)	Physicians + pharmacists. Intervention (5 attending physicians, 5 third year medical residents, 4 second year medical residents, 6 medical interns)	Continued medical training on the most current approaches to the management of hypercholesterolemia.	Usual care^b + access to pharmacy clerk for answering patients’ questions and putting orders for medications.	1. Δ TC. 2. Percentage of patients achieving NCEP goals.	Not described.	1. Δ in TC: I: 44 ± 47 mg/dL vs C: 13 ± 51 mg/dL (P < .001 between groups). 2. Achieving NCEP goals: I: 43% vs C: 21% (P < .05 between groups).	This collaboration improved patients’ outcomes by supporting patients with best therapy advice.
Straka et al, USA¹⁵	Prospective, multiclinic, controlled study	Community (150/331)	18 Months	Combined (Pharmacist educated patients, evaluated initial and subsequent lipid profiles, conducted dosage titrations, recommended therapy changes to physicians and conducted telephone follow-up of patients)	Physicians + pharmacists; Intervention clinics (family practice = 67, internal medicine = 33). Control clinics (family practice = 60, internal medicine = 40)	Physicians received routine medical notifications of the importance of managing hypercholesterolemia from the pharmacists.	Usual care (no clinical pharmacist providing oversight).	1. Δ in LDL during intervention 2. Δ in LDL 18 months after discontinuation of intervention.	1. Patient following instructions for using medication (self report).	1. During intervention: LDL mean ± SD: I: 95 ± 25 mg/dL vs C: 125 ± 28 mg/dL (P < .001 between groups). 2. 18 Months after discontinuation of intervention, 65% of I patients remained at goal (LDL) vs C: 42% (P < .001 between groups). 3. Use of antihyperlipidemic medication increased by 20% in I and declined by 4% in C.	This study showed the sustainability of the impact collaborative care models on improving patient’s outcome.
Tsuyuki et al, Canada¹⁶	Multicentre RCT	Community (344/331)	16 Weeks	Combined (Pharmacist interviewed and educated patients, measured patients’ serum TC level, assessed and reinforced adherence, suggested therapy changes, and conducted in person or telephone follow-up at weeks 2, 4, 8, 12, and 16)	Physicians + pharmacists (from 54 community pharmacies)	Not described	Usual care + informational booklet and advice with minimal follow-up (phone call at 8 weeks, and at study completion 16 weeks).	1. Fasting lipid profile. 2. General Satisfaction with Pharmacy Services Scale.	1. It was considered in the study but not measured.	1. Odds of reaching recommended lipid targets: I: 57% vs C: 31% (odds ratio, 3.0; 95% CI, 2.2-4.1(P < .001 between groups). 2. No significant changes in satisfaction with pharmacy services: I: 16.5% vs C: 20% (P > .05 between groups).	This collaboration improved cholesterol management. Although adherence was not directly measured, the main focus of the intervention was to assess and reinforce adherence in order to improve patient outcomes.
Villeneuve et al, Canada¹⁷	Open cluster RCT	Community (108/117)	12 Months	Informational (Pharmacist provided counseling, recommended lifestyle and therapy changes, scheduled visits, and evaluated patients’ adherence)	Physicians + pharmacists + research nurses. 15 clusters of 51 physicians and 49 pharmacists.	Pharmacists attended a 1 day training workshop.	Usual care + Counseling by pharmacists+ request for lab tests + therapy changes by physicians.	1. LDL-C. 2. Lifestyle changes (self report).	1. Adherence (those patients for whom the amount of medication dispensed covered 80% of no. of days during follow-up period). 2. Persistence (patients had medication dispensed within 60 days before the 12-month visit).	1. The adjusted difference in LDL-C (−0.05 mmol, 95% CI −0.3 to 0.2) was not significant different between groups. 2. 67% patients in I vs 38% in C reported changes in lifestyle RR (95% CI) 1.78 (1.37-2.31). 3. 72% patients in I vs 68% in C reported to adhere to medication RR (95% CI) 1.04 (0.9-1.27). 4. 86% patients in I vs 81% in C reported persistence with medication RR (95% CI) 1.03 (0.94-1.19).	Collaborative primary care was feasible in the management of dyslipidemia without improving adherence and persistence.
Types 2 Diabetes and Hypertension
Litaker et al, USA¹⁸	RCT	Community (79/78)	12 Months	Combined (NPs discussed and established a treatment plan with physicians, conducted telephone management and in-office follow-up, assessed adherence, and educated patients)	Physicians + NPs	NPs were trained on rationale for and application of treatment algorithms.	Usual care.	1. HbA_1c, HDLs, BP. 2. Satisfaction with care and health related quality of life (HRQoL). 3. Personnel costs	1. Evaluated by retrospective chart review at each office visit for each patient.	1. HbA_1c mean changed from baseline (SD): I: −0.63 (1.5) vs C: −0.15 (1.0) (P = .02 between groups); HDLc mean changed from baseline (SD): I: 3.0 (7.2) vs C: 0.4 (6.6) (P = .02 between groups), BP control (11 of 79 I vs 10 of 78 C; P = .839 between groups). 2. No significant difference for HRQoL between groups (P > .05). 3. Cost (SD): I: $58 vs C: $61 (P < .01 between groups). 4. Adherence: I: 100% vs C: 95% (P = .06 between groups).	This collaboration showed significant improvement in disease management and clinical outcomes at modest incremental costs but with no impact on adherence (note: adherence levels were high in both groups).
Hypertension
Borenstein et al, USA¹⁹	Randomized comparative trial	Community (98/99)	12 Months	Combined (Pharmacist determined BP and adherence to medications, reviewed common side effects, educated patients, suggested therapy changes, and conducted visit follow-up)	Physicians + pharmacists + nurses	A guideline was developed and used as a basis for physicians’ education sessions (conducted by pharmacist and other providers).	Usual care	1. BP. 2. Medication costs. 3. Total costs of provider visit.	1. Patient assessments (self report).	1. Achieving BP control: I: 60% vs C: 43% (P = .02 between groups). 2. Monthly medication cost increased more in I than C ($11.31 vs $4.25; P = .12 between groups). 3. Average visit costs/patient: I: $160 vs C: $195 (P = .02 between groups). 4. No result for adherence provided.	This collaboration showed a significant improvement in clinical outcomes and reduction in provider visit costs in intervention group.
Carter et al, USA²⁰	Prospective, cluster-RCT	Community (65/39)	27 Months	Informational (Nurses provided educational information on hypertension and lifestyle changes; Pharmacist interviewed patients and recommended drug changes to the physicians)	Physicians + pharmacists + research nurses	The nurses were specially trained and certified quarterly to measure BP. Physicians received extensive education on the JNC-7 guidelines.	Usual care + providing patients with educational information on hypertension and lifestyle modifications.	1. BP during study (9 months). 2. BP after study discontinuation (18 and 27 months).	1. Pill counts	1. During study: I: 78.5% vs C: 48.7% reached BP goals (P = .0017 between groups). 2. At 18 months BP control: I: 53.9% vs C: 30.8% (P = .02 between groups) and at 27 month, BP control: I: 55.4% in I vs C: 35.9% (P = .05 between groups). 3. Adherence improved in both groups: I: 98.9 ± 12.2% vs C: 92.6 ± 11.8% (P = .20 between groups).	This collaboration had positive effect on maintaining BP during and after intervention. Although adherence was largely improved in both groups but there was no significant difference between groups.
Carter et al, USA²¹	Cluster RCT	Community (192/210)	6 Months	Informational (Pharmacist assessed medications and BP and recommended drug changes to physicians)	Physicians + pharmacists + research nurses. 6 community family medicine clinics (I: n = 3; C: n = 3)	Educational lectures+ published national guidelines + clinical trial evidence.	No care was provided by clinical pharmacists only BP was measured at baseline, 3 and 6 months.	1. BP control.	1. Validated self-report questionnaire.	1. BP controlled: I: 63.9% vs C: 29.9% (P < .001 between groups). 2. Adherence: I: 8.9% vs C: 9% (P > .99 between groups).	Adherence to medication did not significant differ between groups (low rates in both groups) although this collaboration showed a significant improvement in BP control.
Carter et al, USA²²	Prospective, cluster RCT	Community (101/78)	9 Months	Combined (Pharmacist interviewed patients, assessed patients’ regimens, provided therapy recommendations, recommended adherence aids, and educated patients)	Physicians + pharmacists + research nurses. 5 clinics	Educational lectures and training sessions+ team-building exercises²³.	Usual care	1. BP control. 2. Adverse reaction assessments.	1. Pill counts.	1. BP controlled: I: 89.1% vs C: 52.9% (P < .01 between groups). 2. No change in adverse reaction assessment (P = .135 between groups). 3. Adherence: I: 94% vs C: 92% (P = .369 between groups).	Adherence was not significantly different between groups although this collaboration showed significant improvement in achieving overall BP control rates.
Hunt et al, USA²⁴	Single-blind RCT	community (142/130)	12 Months	Informational (Pharmacist reviewed medications and lifestyle habits, provided education, assessed medication side effects that are experienced, identified barriers to adherence, and scheduled follow-up appointments)	Physicians + pharmacists. 5 clinics, 80 physicians	1-2 years of ambulatory medicine residency training for pharmacist without any further training.	Usual care + scheduled an appointment with primary care physicians.	1. BP. 2. Resource of utilization (patients’ total no. of clinic visits). 3. Quality of life (QoL) and satisfaction.	1. Self-administered questionnaire.	1. Odds of achieving BP target: I: 2.08 times >C (P = .003 between groups). 2 Resources of utilizations: I: 3.2 vs C: 4.7 (P < .0001 between groups). 3. No significant differences between groups in QoL (P > .05). 4. Adherence: I: 67% vs C: 69% (P = .77 between groups).	Intervention subjects demonstrated an increase in adherence from baseline to end of study although there was no significant difference between the two groups.
Murray et al, USA²⁵	RCT	Hospital outpatients (171/541)	12 Months	Informational (Physicians’ intervention: provided patients with education material, printed visit notes, and wrote medication orders; Pharmacists’ intervention: filled prescriptions and discussed drug/dosage change recommendations with physicians)	Physicians + pharmacists	A presentation of JNC VI guidelines and the role of computer decision support systems in improving patients’ outcomes.	Usual care	1. Generic HQoL. 2. Symptom and side effects profile. 3. BP control	1. Medication possession ratio.	1. No differences in HQoL scores between groups (P > .05). 2. No significant differences in symptoms and side effects between groups (P > .05). 3. BP: little change at 6 months. 4. No significant difference in ccompliance to all treatment suggestions between groups (P = .13).	This collaboration had a little impact on improving patients’ compliance to therapy as well as other outcomes.
Von Muenster et al, USA^26,c	RCT (single group design)	Community 101 (only I)	9 Months	Combined (Pharmacist interviewed patients, identified problems for poor BP control, educated patients, developed a new treatment plan, recommended therapy and lifestyle changes, and conducted visit follow-up)	Physicians + pharmacists + research nurses. 2 family medicine clinics + 5 clinical pharmacists	Research nurses certified every 3 months to ensure their ability to measure BP.	None	1. BP control. 2. Pharmacist therapy recommendations to improve adherence. 3. Physicians acceptance of pharmacists’ recommendations.	1. Adherence was considered in the study but not measured.	1. 89.1% (P < .01) of patients had achieved BP goal. 2. Average no. (±SD) of recommendations to change medications to improve adherence was 3.57 ± 1.40 per patient. 3. Physicians accepted 95.9% of pharmacist’s recommendations.	This collaboration between pharmacists and physicians was effective in improving patients’ outcomes. Most of the therapy recommendations were aimed at improving adherence to therapy.
Svarstad et al, USA²⁷	RCT	Community (25/25)	12 Months	Behavioral (Pharmacists provided patients with adherence aids, eg, pill organizers, tailored medication schedule and conducted visit follow-up)	Physicians + pharmacists + pharmacy technicians. 14 TEAM care pharmacy vs 14 usual care pharmacies.	Pharmacists and pharmacy technicians trained via interactive workshop by medical educators using a range of methods.	Usual care	1. BP	1. BMQ, Pharmacy prescription profiles + refill.	Preliminary results provided: 1. Improved BP. 2. Improved adherence to medication.	Pharmacists had a crucial role in improving patient’s clinical outcomes and adherence to medication by providing useful information for patients and physicians.
Santschi et al, Switzerland²⁸	Cluster RCT	Community (34/34)	12 Months	Behavioral (Physicians and pharmacists supplied patients with MEMS, trained patients on how to use MEMS, explored the ways to improve adherence, suggested medication regimen changes, and scheduled visits for patients)	Physicians + pharmacists. 8 networks of community pharmacies	Not described	Usual care without any special effort being made to improve patient's adherence.	1. BP	1. MEMS	1. Reaching target BP: I: 27.2% vs C: 13.2% (P < .05 between groups). 2. Adherence in I group was very high with a median taking adherence of 96% (range: 78.8–100.0).	This collaboration focused on monitoring adherence to medication, and lead to improved outcomes for the subjects.
Weber et al, USA²⁹	RCT	Community (92/68)	9 Months	Informational (Pharmacists interviewed patients, evaluated patient factors that affect achieving BP goal, and provided recommendations on medication changes to physicians)	Physicians + pharmacists + research nurses. 5 university-affiliated primary care clinics	Research nurses were certified every 3 months to ensure they were able to measure BP.	Usual care + research nurse structured data collection visits.	1. ADR. 2. Social support questionnaires.	1. Self-efficacy Questionnaire (scores range from 27-135, with higher numbers indicating higher self-efficacy).	1. ADR scores decreased in both groups (I: 29.9-22.7 vs C: 26.5-18.4; P > .05 between groups). 2. No Δ in social support (I: 7.93 vs C: 7.79); P > .05 for either group. 3. Self efficacy scores: I: (121. 01-124.35, P = .0005) vs C: (123.49-124.21, P > .05); (P > .05 between groups).	This collaboration successfully improved subjects’ self efficacy and resulted in minimizing ADRs.
Heart Failure
Kasper et al, USA³⁰	Prospective RCT	Hospital outpatients (102/98)	24 Months	Combined (CHF nurses implemented therapy plan design by CHF cardiologists, adjusted medication dosage, provided patients with a pill sorter and a list of correct medications, provided education materials, and conducted follow-up visits)	Cardiologist + CHF nurse+ telephone nurse coordinator + physician	Not described.	Usual care+ therapeutic plan was documented by cardiologist in the patient’s chart.	1. No. of CHF hospital admissions. 2. Death. 3. Δ in HRQoL	1. Adherence to medication (not described how measured). 2. Dietary compliance (by using dietary sodium score).	1. Hospital admissions: I: 43 vs C: 59 (P = .09 between groups). 2. No. of patients died: I: 7 vs C: 13(P = .09 between groups). 3. Significant difference in HRQoL between groups (P = .003). 4. No significant difference in adherence between groups (P > .05). 5. Significant difference in dietary compliance between groups (P = .002).	This multidisciplinary team approach successfully improved clinical outcomes and dietary compliance but not medication compliance.
High-Risk Diseases (Involving Cardiovascular Diseases)
Farris et al, Canada²³	A single group pre–post design	182 patients	6 Months	Behavioral (Pharmacists conducted home visits for medication reviews, conducted telephone follow-up, and documented any identified health issues).	Family physician + pharmacist+ nurse. 6 primary health care teams	Team development training was provided and the meetings were conducted every week to discuss patients’ health problems.	None	1. Physical health component (at 3 and 6 months). 2. Mental health component. (at 3 and 6 months). 3. No. of physician visits, hospital admissions, and emergency department visits.	1. Self-reported measure at 3 and 6 months (0-4 scale, where 4 indicates best compliance).	1. Physical health score improved at 3 months (38.44 ± 11.39 compared to 36.99 ± 10.25 at baseline; (P = .01). 2. Mental health remained unchanged at 3 and 6 months. 3. Trend toward fewer hospital admissions, physician, and emergency department visits. 4. Medication compliance baseline score of 2.91 ± 1.03 improved to 3.16 ± 0.95 at 3 months (P < .01); and was sustained at 6 months (baseline score of 2.85 ± 1.01 improved to 3.13 ± 0.90; (P = .02)).	Most of HCPs found this collaboration was useful in improving patient compliance.

Abbreviations: I/C, intervention/control groups; HCPs, health care professionals; RCT, randomized clinical trial; TC, total cholesterol; Δ, change; I, intervention group; C, control group; NCEP, National Cholesterol Education Program; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; NPs, nurse practitioners; HbA_1c, pre- and post-study glycosylated hemoglobin; SD, standard deviation; HDLc, high-density lipoprotein cholesterol; BP, blood pressure; HRQoL, satisfaction with care and health-related quality of life; JNC-7, The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; QoL, quality of life; JNC-VI, The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; HQoL, satisfaction with care and health quality of life; BMQ, brief medication questionnaire; ADR, adverse drug reaction; CHF, chronic heart failure; RR, relative risk; TEAM, The Team Education and Adherence Monitoring; MEMS, Medication Events Monitoring System.

^aOnly some studies mentioned the number of HCPs delivering the service to the patients.^{14-16,21-24,26-29}

^bUsual care group refers to the group of patients who received the “usual care” from their physicians and their pharmacist without any different service being provided. This group may also be referred to as the study “control group”. Usual care has been outlined in table where the authors have described the usual care received by the subjects.

^cOnly reported results of the intervention arm of study 21.²⁶

These 17 articles described 16 randomized controlled trials,^{14

–22,24

–30} and 1 single group pre–post design.²³ Of the 17 articles, 7 described and evaluated informational interventions,^{14,17,20,21,24,25,29} 3 described and evaluated behavioral interventions,^23,27,28 while 7 described and evaluated combined interventions.^{15,16,18,19,22,26,30}

Of the 7, only 2 studies of informational interventions^20,29 demonstrated improvements in measured adherence to medications. However, the improvements were not significant. On the other hand, most of the studies (5 of 7) showed a significant impact on reaching target clinical outcomes.^{14,17,20,21,24}

All behavioral interventions (3 of 3) improved both adherence and clinical outcomes.^23,27,28 In contrast, none of the combined interventions led to improved adherence to medication, but all (7 of 7) showed significant improvements in clinical outcomes. However, one of the studies demonstrated a significant impact on improving compliance to a dietary regimen,³⁰ while another study¹⁵ showed an increase in the percentage of patients appropriately following the given instructions for the use of their medications.

Based on the selection criteria, all interventions were directed by more than 1 HCP. Physicians and pharmacists^{14
–16,24,25,28}; physicians, pharmacists, and research nurses^{17,19

–23,26,29}; physicians and nurse practitioners¹⁸; cardiologists, CHF nurses, telephone coordinators, and physicians³⁰; and physicians, pharmacists and pharmacy technicians²⁷ were responsible for delivering health care services to patients.

Training of HCPs

Most of the studies reviewed and described the methods used to train HCPs with the exception of 3 studies that did not indicate whether or not HCPs had been trained.^16,28,30 The training was primarily workshop based, and within the workshops, a range of methods were used to improve HCPs’ skills in communication, diagnosis, measuring outcomes, and improving patient adherence to medications. These training methods included a mix of lectures, slides, presentations, demonstrations, role-playing, and discussions. In 5 studies,^{14,17,21,22,27} HCPs attended a training workshop or sessions conducted by medical educators, pharmacists, or physicians, where didactic lectures, role-playing, clinical trials evidence, and interactive exercises were used to present information about disease physiology, treatment protocols, and communication strategies to optimize adherence to medications. In a study,¹⁷ HCPs were also invited to a meeting aimed at discussing the intervention and progress of patients’ clinical outcomes, a month after attending the training workshop. An evidence-based guideline or algorithm (eg, The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [JNC-7]) for management of diseases^18
–20,25 was provided to a multiprofessional group of HCPs (physicians, pharmacists, and nurses) through a presentation with instructions on rationale for and application of treatment algorithms. A computer decision support system (to improve quality of patient care) was used in a study.²⁵

In 2 studies, HCPs^22,23 underwent team building exercises to explore strategies to optimize treatment and improve patient adherence to medications. In addition, there were follow-up discussions to debrief HCPs on the implementation issues related to the intervention.^22,23 In a study,²⁴ HCPs did not receive any training as it was felt that 1 to 2 years of ambulatory medicine residency training was considered sufficient. In some studies, training was provided to research nurses followed by quarterly certifications in BP measurement techniques.^20,26,29

Interventions Delivered by HCPs

In a number of studies,^{14

–17,19

–24,27
–29} the interventions were delivered by a clinical pharmacist after discussing a specific patient care plan with the patients’ physician. Each plan was implemented by the clinical pharmacist and could involve one or more of the following: prescribing drug therapy, adjusting medication dosage, providing counseling, and recommending lifestyle changes. In addition, the clinical pharmacist provided patient education, ordered and evaluated results of blood tests, titrated doses of medications (ie, starting with a low dose then titrating the dose with close monitoring based on patient response and tolerability), assessed patients to determine adherence to their medications and lifestyle changes (healthy diet, weight loss, and exercise), and made recommendations for changes in therapy. The pharmacists reported and discussed the results of their patient interviews with physicians. While the pharmacists provided most of the drug therapy recommendations directly to the physician during the patient visit, some physicians authorized the pharmacist to make dosage changes and to record them in a case report format. In most of the studies, patients were followed-up for several months. Except for one study,²³ home care nurses contacted patients’ home care case manager or the patients directly to collect the important health information to be discussed at the next team meeting.

In other studies,^{20
–22,26,29} research nurses collected the patients’ demographic data, measured height and weight, recorded antihypertensive medications, doses, and dates of last refills; they also performed pill counts of BP medications and queried patients for possible adverse reactions. Patients’ BP was measured at each data collection visit and requests were forwarded to the pharmacists and/or physicians.

In another study,¹⁸ a care team consisted of primary care physicians and nurse practitioners (NPs). Initially, NPs were trained on the rationale and application of treatment algorithms for chronic disease management. Subsequently, the NPs only discussed with the patient’s physician management decisions or problems that were not initially addressed in the algorithms and a treatment plan was established accordingly. During each follow-up visit, NPs were responsible for developing therapy regimens focusing on the assessment of adherence to medication, individual barriers to adherence, and family support for treatment.

A computerized treatment decision support was used in the study by Murray et al.²⁵ After physicians examined the patients, requisitions for drugs, tests, nursing, and consultations were made using order-writing workstations. The workstation identified treatment suggestions for hypertension for each eligible patient. Subsequently, educational materials were provided to the patients, while all the treatment suggestions were transmitted to pharmacists through a computer-based ordering system. Once pharmacists received the treatment suggestions, they had 3 options: fill the prescriptions as written, discuss the intervention suggestions, and encourage subsequent discussions with patients’ physicians or contact the physicians either by telephone or by page.

In another study concerning heart failure patients,³⁰ telephone nurse coordinators followed up the patients by telephone to pursue their clinical problems without adjusting their medication over the telephone. The chronic heart failure (CHF) nurses later met the patients each month to adjust medications under the supervision of cardiologists who designed a treatment plan for all study patients. The primary physicians received regular updates from the CHF nurses and were informed of any abnormal laboratory values for the patients. All team members, except patients’ primary physicians, participated in weekly patient care meetings.

Discussion

Relatively little research has been published on adherence enhancing interventions delivered by teams of HCPs to patients with CVD. Our review findings suggest that the interventions involving physicians, pharmacists, nurses, and other health care providers to improve patient’s clinical outcomes and optimize adherence to medications achieved better results in the patients who received the intervention compared with control patients. This lends support to the notion that HCPs working in teams can effectively improve patients’ clinical outcomes and therefore positively impact their health. However, evidence for what constitutes the most effective model of collaborative practice among pharmacists, physicians, and nurses to support and enhance adherence to medication and persistence among patients was not identified in this review.

Almost all the studies (14 of 17) demonstrated significant improvements in clinical outcomes, while only 3 studies showed significant improvements in both adherence to medications and clinical outcomes. We found that among the studies reviewed, those based on behavioral interventions improved both adherence and clinical outcomes. In contrast, studies which used informational and combined interventions appeared to have little or no impact on improving adherence to medications. Although combined interventions included both behavioral and informational components, they did not result in improved patient adherence to medications. This could be due to several reasons, including how effectively the HCPs were trained in delivering the interventions, in turn how well they delivered the interventions, the patients groups, the study design, and the differences in the relative contribution of each element to the intervention. Additionally, there were limitations because of the study designs. Many of these studies did not measure adherence as it was not considered a primary outcome. For example, in the studies by Tsuyuki et al¹⁶ and Bogden et al,¹⁴ adherence was not directly measured, although it was a key focus of the pharmacists’ intervention. Improved clinical outcomes resulted when pharmacists’ therapy recommendations were formulated to intensify therapy to reach therapeutic targets and at the same time to improve adherence to medications. Furthermore, the method of measuring adherence was not described in some of the studies.²⁶

Another reason for failure to detect any changes in adherence to medications rests in the approach to its measurement. A wide variety of measurement methods and definitions of adherence were utilized in the studies. Self-reports and pill counts were the most commonly used methods of measurement. However, in some studies, validated self-report questionnaires were used.

In most studies, the collaborative care work or the intervention that was directed by more than one HCP leads to improvements in patient clinical outcomes and adherence to medications. This may be due to the fact that HCPs were working together to deliver quality and sustainable health care to patients. From a patient safety point of view, well-functioning teams have great promise to deliver superior care. In contrast, poorly functioning and, in particular, poorly communicating teams increase the chance of harm to patients.¹⁶

Most HCPs received training, which had a positive impact on improving patient outcomes and to a lesser extent adherence; this suggests that there may be a positive correlation between the degree of impact and the extent of training received.^{15,18,20
–22} A 1 day training workshop for HCPs,¹⁷ however, may not have been sufficient to equip the HCPs with the skills required to improve patients’ outcomes and adherence to medications.

In most of the studies, pharmacists were pivotal in delivering the intervention or collaborative care to the patients as they were responsible for titrating patients’ medication, counseling, interviewing, providing education, identifying barriers to adherence, and scheduling follow-up appointments. The majority of pharmacists made therapy recommendations during the interventions to improve disease management and adherence to medications. In most cases, decisions were made collaboratively by the physicians and pharmacists. However, most physicians agreed with the pharmacists’ recommendations due to physicians’ satisfaction with such collaborative care that may potentially lead to improvements in patients’ clinical outcomes, but only small improvements in patients’ adherence to medications.

On the other hand, some collaborative care did not have any impact on improving clinical outcomes or adherence. For example, results from 2 studies^17,25 reported no improvements in both adherence and patients’ health outcomes. This may be due to either the randomization of a small number of clusters or to the weakness of the delivered interventions. In addition, it seemed that physicians did not actively deal with each suggestion given by pharmacists due to the complexity of suggestions or the time-consuming nature of addressing the suggestions.²⁵

Conclusions

This review evaluated the effectiveness of multiprofessional interventions aimed at improving patients’ adherence to medications. Behavioral interventions delivered by a multiprofessional team appear to offer the best opportunity to improve clinical outcomes through improvements in adherence. However, whether interventions delivered by a multiprofessional team are more clinically effective than those delivered by a single HCP remains to be tested.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Multiprofessional Interventions to Improve Patient Adherence to Cardiovascular Medications

Abstract

Background:

Objective:

Search strategy:

Selection criteria:

Results:

Conclusions:

Keywords

Introduction

Cardiovascular Disease

Management of CVD

Adherence to CVD Medications

Interventions Aimed at Improving Adherence to Cardiovascular Medications

Objectives

Method

Criteria for Considering Studies for this Review

Types of studies

Types of participants

Types of patients

Types of interventions

Types of outcome measures

Exclusion Criteria

Results

Training of HCPs

Interventions Delivered by HCPs

Discussion

Conclusions

Footnotes

Declaration of Conflicting Interests

Funding

References