The Most Effective Patient Adherence Interventions of ... · 15 comparative group and reported...

ISPOR Medication Adherence and Persistence SIG DRAFT for REVIEW

1

The Most Effective Patient Adherence Interventions of Lipid Lowering Medications - A Systematic Review of the Literature: A

Report of the ISPOR Medication Adherence and Persistence Special Interest Group

Authors: Maribel Salas, MD, DSc, MSc. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, USA, and Patient Safety, AstraZeneca, Wilmington, Delaware. Stephen Glasser, MD. Division of Preventive Medicine and School of Public Health, University of Alabama at Birmingham. Dyfrig A. Hughes, BPharm, MSc, PhD, MRPharmS, Professor of Pharmacoeconomics, Centre for Economics and Policy in Health, Bangor University, Bangor, Wales, UK. Femida H. Gwadry-Sridhar BSc Pharm, MSc(Epi), PhD. Research Professor, Dept. of Computer Science, Adjunct Physiology & Pharmacology, and Director of Health Informatics, Lawson Health Research Institute, London, ON Canada. Elizabeth Manias, RN CertCritCare, BPharm MPharm MNStud, PhD, FRCNA MPSA. Professor, Associate Head of Research, Melbourne School of Health Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, VIC, Australia. On behalf of ISPOR Medication Adherence and Persistence Special Interest Group.


2

Abstract

Background: Lipid-lowering medications have well established benefits in primary and secondary 1

prevention of cardiovascular disease. However, patient adherence to these medications continues to be 2

poor. Efforts to improve adherence might help patients benefit more fully from this evidence-based 3

therapy. 4

5

Objectives: To determine the most effective interventions to improve patient adherence with lipid 6

lowering medications. 7

8

Methods: We conducted a systematic review using Medline, Cumulative Index to Nursing and Allied 9

Health Literature, EMBASE, Cochrane Library, and references of review articles, and meta-analyses. 10

We screened abstracts of studies published from 1999 to 2011, irrespective of language that included 11

the terms: hyperlipidemia, hypercholesterolemia, lipid lowering medications and adherence, adherence, 12

and interventions. Studies with incomplete information, lack of adherence measures, overviews and 13

letters to editors were excluded. Full articles of studies on interventions that reported the use of a 14

comparative group and reported quantitative data on adherence were included. Two independent 15

researchers reviewed papers, and disagreements were agreed to by consensus. A standardized data 16

form was used to extract data. A study quality score was calculated using the Downs modified scale. 17

18

Results: Of 130 titles, 80 abstracts were screened and only 14 studies fulfilled the inclusion criteria. 19

Study heterogeneity precluded a quantitative meta-analysis. Most interventions improved drug 20

adherence by 2% to 40% and only two increased by more than 50%. Most studies focused on 21

pharmacist-led interventions, and included telephone reminders, card reminders, brochures, and 22

booklets. All interventions were able to reduce low density lipoprotein (LDL) and/or total cholesterol. 23

Average index quality score was 62%. 24

25

Conclusions: The most effective interventions to improve adherence with lipid lowering medications are 26

multi-factorial interventions. Interventions focused on improving adherence are able to reduce LDL and 27

total cholesterol. However, reports are of variable quality. 28

29

Key words: interventions, patient adherence, adherence, persistence, cardiovascular, lipid-lowering 30

medications, lipids and meta-analysis. 31

32

Acknowledgement 33

Authors are members of the International Society for Pharmacoeconomics & Outcomes Research 34

(ISPOR) Medication Adherence & Persistence Special Interest Group 35

36


3

Introduction 37

Cardiovascular disease is a leading cause of death, and causes more than 4 million premature deaths 38

each year, 18% of global cerebrovascular disease (mostly non-fatal events) and 56% of global ischemic 39

heart disease; and, hyperlipidemia is one of the most important risk factors. [1]. Controlling risk factors 40

through pharmacologic treatment can reduce morbidity and mortality [2, 3] and reduce costs of care [4]. 41

There is evidence from clinical trials that statin therapy is effective in reducing cerebrovascular and 42

cardiovascular morbidity and mortality [5, 6, 7]. However, the benefits of lipid lowering drugs are 43

compromised by poor adherence. 44

Non-adherence with lipid lowering medications has been estimated at approximately 50% over 5 years 45

[8] with the highest frequency of drug discontinuation occurring in the first year of treatment [8,9,10]. 46

Many factors have been related to poor adherence such as knowledge about health beliefs, uncertainty 47

about the benefits of lipid lowering treatment, risk perception, concerns or experiences with side effects 48

of medications, costs of medications, and inconvenience [11, 12]. Poor adherence has been associated 49

with poor outcomes particularly increased hospitalization rates and increased medical costs [13,14]. 50

Various interventions have been developed to increase medication adherence such as modifying drug 51

dosing schedules and/or packaging, combining lipid-lowering medications with other drugs, using 52

educational materials for health care providers and/or patients, and promoting self-management 53

programs [15], but contradictory results have been published on the effects of some interventions such 54

as mail and telephone reminders [16]. 55

The objective of this review is to determine the most effective interventions reported to improve patient 56

adherence with lipid lowering medications. 57

58

Methods 59

Searching 60

We conducted a systematic review using the following databases: Medline, Cumulative Index to Nursing 61

and Allied Health Literature (CINAHL), EMBASE, and Cochrane Library. We also searched the 62

bibliographies of review articles, and previous meta-analyses. 63

Two investigators searched independently and screened abstracts of studies published from January 1, 64

1999 to July 31, 2011, limited to adult humans, irrespective of language that included the terms: lipids, 65


4

hyperlipidemia, high cholesterol, hypercholesterolemia, lipid lowering medications and adherence, 66

adherence, persistence and interventions, patient-focused interventions. 67

68

Selection 69

We included full articles of trials on patient-focused interventions that reported the use of a comparative 70

group and reported quantitative data on adherence. Some studies reported usual care, defined as the 71

standard care provided to patients. Information related to clinical outcomes (e.g. serum cholesterol 72

levels, reduction of hospitalization, reduction of CVD events, etc) was also recorded. 73

Studies with incomplete information on the intervention, lack of adherence measure, overviews and 74

letters to editors were excluded. 75

76

Quality assessment 77

The Down modified scale was used to assess the quality of each study. The original checklist contained 78

35 items, but five of them were related to health economic models, and were not considered applicable 79

to the studies included in the review [17]. We assigned a score of 1 if an article included the required 80

item, and zero if it was not included. Therefore, the maximum score for an article that included all 81

information related to study design, data collection, analysis and interpretation of results was 30 [18]. 82

83

Data Abstraction 84

The same two independent researchers reviewed each article and disagreements were resolved by 85

consensus. A standardized data form was used to extract the following information: complete reference, 86

study design, randomization, double-blind, use of control group, type of intervention in the study group 87

and also in the control group, patient characteristics, measure of adherence, clinical measurements, 88

follow-up time, ethical considerations (e.g. study approved by an Ethics Committee), sample size (total 89

and in each group), statistical analysis, assumptions and control of confounding factors, adherence and 90

clinical results. After extracting the information, we applied the quality score. 91

92

93

94


5

95

Data Analysis 96

Given the heterogeneity of patient population, type of adherence measurements and clinical outcomes, 97

and reported results of adherence and clinical outcomes, we decided to carry out a qualitative review 98

rather than a meta-analysis. 99

Descriptive statistics were used when appropriate to describe some characteristics of the patient 100

population. 101

102

Results 103

Study characteristics 104

Eighty abstracts were screened and 66 were excluded because they were reviews (16), letters to 105

editors (2), did not have an adherence intervention (46), or there were no quantitative data on adherence 106

(2). Fourteen studies fulfilled all inclusion criteria (Figure 1). 107

In these 14 studies [36,37,38,39,40,41,42,43,44,45,46,47,48,49], the majority of interventions were 108

administered by pharmacists (43%) [36,38,39,42,43,49] followed by physicians (36%) [41,44,45,47,48], 109

and other health care professionals (7%) [37]. In 14% of studies there were no reports on who 110

administered the intervention, and ten studies used randomization to distribute individuals to each arm 111

[37,39,40,43,44,45,46,47,48,49]. Most studies were carried out in medical centers (50%) followed up 112

by pharmacies and community clinics. In all, 57% of interventions were intensified patient care followed 113

by patient education (29%) and medication management (14%). Some interventions were part of 114

disease management programs defined as systems of coordinated health care interventions and 115

communications for patients with chronic conditions. Interventions comprising intensified care consisted 116

of phone calls (3), use of electronic systems (1), mail reminders (3), and close physicians’ monitoring 117

(1). Education was provided using pamphlets, slide kits and counseling, and medication was managed 118

using tracking and alerting systems. In one study, physicians showed patients, patients’ own carotid 119

images. Most studies used usual care as a comparator (11 studies), while in the rest of studies 120

[37,38,39,40,42,43,44,45,46,47,48], patients were their own controls [36,41,49]. 121

In relation to adherence, there was an important variation in the measurements: renewal rates, refills, pill 122

counts, self report, MEMS; and in five studies, investigators used more than one adherence measure: 123


6

self reported and pill count (2), self reported and refills (1), and refills and pill count (2). Most studies 124

(71%) reported the use of clinical outcomes such as laboratory measurements of LDL-C, HDL-C, TG, 125

and total cholesterol, and only one study included a diet intake questionnaire. 126

The target population varied considerably from asymptomatic, newly diagnosed hypercholesterolemic 127

patients to adults who underwent coronary revascularization or who had other comorbidities such as 128

diabetes. There were more than 20,000 patients in total. Only three studies reported confounders 129

[37,38,41], and three of them did not report IRB approval. The follow-up time also varied from two 130

weeks to 43 months, and only five studies reported the number of patients who were lost during the 131

follow-up period. 132

Most interventions increased adherence from 2% to 40%, and only two increased adherence more than 133

50% (Figure 2). A disease management study using a community pharmacits reported an increment of 134

15.3% of prescription renewal dates after six months of follow up. Compared to control groups, patient 135

adherence interventions personalized telephone calls had higher impact in long-term adherence than 136

usual care. The overall adherence was 62% at one year and 55% at two years for the study group 137

compared to 37% and 31% for the comparator group. When patients were exposed to their carotid 138

imaging results, they were 10 times more likely to adhere with their treatments [41]. 139

The most effective type of intervention was intensified patient care where multiple subinterventions were 140

administered to patients (e.g. medication education and regular follow-up by pharmacists or using other 141

types of reminders). In terms of populations, the most effective intervention was observed in patients 142

who underwent coronary artery revascularization with which there was a 25% increase in adherence 143

after one year of follow up. Studies had an overall quality score of 62%. 144

145

Discussion 146

We found that the most effective type of interventions to increase patient adherence was intensified 147

patient care, which involved complex interventions administered to patients. This is important to 148

consider especially when decisions need to be made about selecting the most appropriate intervention 149

to increase medication adherence. It was interesting to find that patients who already experienced 150

disease- related complications and required surgical procedures were the most receptive population to 151

comply with treatment [37,38,39,49], probably because patients might have believed that they could 152


7

revert the complication. It was clear that even with complex interventions, only two interventions could 153

increase adherence to more than 50%, which reflects the difficulty to change behaviour. Therefore, it is 154

necessary to continue looking for interventions to increase patient adherence to lipid lowering 155

medications which will impact on cardiovascular outcomes [19, 20] since high levels of adherence are 156

associated with reductions in adverse clinical outcomes including all-cause mortality and non fatal 157

cardiovascular events especially when adherence levels are 80% or greater [21]. Furthermore, it is 158

known that non-adherence decreases the survival benefit established in clinical trials by 50% [22]. 159

We also found that disease management interventions are the most effective interventions to increase 160

adherence and persistence with long term treatments, and thi is an important finding when planning 161

long-term programs, especially when we know that cholesterol-modyfying therapy have shown 162

established benefits in the primary and secondary prevention of coronary heart disease and stroke [23]. 163

Despite the variation of interventions with long-term effect, heath care professionals should closely 164

monitor adherence since this is a dynamic process and patients need prompt responses to their 165

questions and resolution of any issue to continue with treatment. Efforts to organize collaborative 166

interdisciplinary disease management teams have shown to improve adherence [1,24, 25]. In addition, 167

follow-up visits and serial lipid testing have also shown to be effective [26]. Most notably, the studies we 168

reviewed suggested that patients observation of their own images, particularly the lipids deposits on their 169

arteries, is a high motivator to keep them on therapy. 170

Although, some studies have reported various causative factors associated with poor adherence such as 171

younger age, female sex, fewer comorbidities, greater out-of-pocket costs [27, 28], adverse effects, 172

improper instruction, patient forgetfulness, and lack of belief in benefit [29]; there is limited information 173

about such causative factors associated with poor adherence among participants of interventions. 174

Some studies have investigated how to improve patient adherence to lipid lowering medications and 175

they recommended extending the time of patients with their physicians to discuss their medications, 176

especifically information about the benefits, risks and resasons to prescribe a drug, advice about class 177

effect of medications, drug interactions; and provision of follow up reminders and mail medications to 178

patients [Fung]. Some studies have shown that better communication and trust between health care 179

providers and patients increases patient adherence to treatment [30]. It was interesting that only one 180

study tested the impact of using MEMS to monitor the usage of oral medication. Although the efficacy of 181


8

MEMS is widely known [31], there is an assumption that opening the medication container is associated 182

with consumption of the dose but clinical data is necessary to confirm adherence [32]. 183

An important question relates to the costs of interventions to enhance adherence. Some studies have 184

reported that nurse-led interventions is one of the most cost-effective interventions with incremental 185

costs of $14,100 per quality-adjusted life year gained [33].It has been suggested that high risk patients 186

should received educational programs focused on areas of patients’ concerns such as safety and it 187

should emphasized the long-term benefits of adherence [lardizabal], and this will increase the 188

cost/benefit ratio of interventions. 189

We recognize some limitations of our study particularly the variations in 190

patient population, definition and measures of adherence, use and selection of comparator groups, 191

information based on trial data rather than real world data and potential publication bias. Although trial 192

data are important to determine whether an intervention works or not, the artificial environment and 193

controlled environment limit their translation in the real world. 194

In terms of interventions, there is limited information on what specific components of the intervention are 195

the key elements to achieve outcomes, how difffering levels of applications of interventions impact 196

outcomes and what other factors could increase the effect of the intervention [34]. Further, it is also 197

unclear whether the interventions are reproducable as they were not always validated or well-defined. 198

There are future opportunities to build on what we have found: that being that complex interventions may 199

have benefit – particularly if they are multifaceted. We know from education theory that people need to 200

be exposed to information several times, often using different communication modalities (audio, video, 201

text) to have a lasting effect [35]. We also found that visualization may have an important role in 202

behaviour change – an area that should be further supported. Therefore, future studies should be 203

focused on answering these important questions. 204

205


9

Figure 1. Flow diagram of studies 206

207

208

209

210

211

212

213

214

215

Identified abstracts = 80

Excluded

Reviews = 16

Letters to editors = 2

Lack of intervention = 46

No quantitative data on adherence =2

Studies that fulfilled inclusion criteria = 14


10

Table 1. Study Design and Type of Intervention by Study

Reference Study Design Type of Intervention

Research Question, Objective and/or hypothesis

Place and Time

Randomization Double-blind

Control Group

Ali F, Laurin MY, Lariviere C, Tremblay D, Coutier D. The effect of pharmacist intervention and patient education on lipid-lowering medication compliance and plasma cholesterol levels. Can J Clin Pharmacol 2003;10:101-6 [36].

To determine the impact of community pharmacist pilot disease management program on patient adherence with lipid lowering drugs and on serum cholesterol levels.

Seven pharmacies, from Nov 1999 to Sep 2000

No Not Reported

Subjects were their own control

Pharmacist

Allen JK, Blumenthal RS, Margolis S, Rohm YD, Miller III ER, Kelly K. Nurse case management of hypercholesterolemia in patients with coronary heart disease: Results of a randomized clinical trial. American Heart Journal 2002;144(4):678–86 [37].

To test the effectiveness of a nurse case management program to lower blood lipids in patients with CHD. To compare the effectiveness of a nurse case-management program of individualized lifestyle modification and pharmacologic intervention to lower blood lipids with a less intensive intervention of usual care enhanced with feedback on lipids in adults with dyslipidemia after coronary revascularization

Large tertiary medical center

Yes Not Reported

Yes Nurse

Bozovich M, Rubino CM, Edmunds J. Effect of a clinical pharmacist managed lipid clinic on achieving National Cholesterol Education Program low-density lipoprotein goals. Pharmacotherapy 2000;20 (11):1375–83 [38].

To test the benefits of a clinical pharmacist- managed lipid clinic on lipids profile (HLD, LDL, TG), patient adherence with treatment, and enhance patient knowledge on lipids management.

Eagle Cardiology Group, Jan 1, 1998-

No No Yes Lead intervention by clinical pharmacist (60 min consultation) that were receiving care by cardiologist.


11

Faulkner MA, Wadibia EC, Lucas BD, Hilleman DE. Impact of pharmacy counseling on compliance and effectiveness of combination lipid-lowering therapy in patients undergoing coronary artery revascularization: a randomized, controlled trial. Pharmacotherapy 2000;20(4):410–6 [39].

To assess the impact of personalized telephone follow up on the rate of adherence in high risk, hypercholesterolemic patients receiving combination drug therapy.

St. Joseph Hospital in Omaha, Nebraska.

Yes, using computer-generated list of random numbers.

Not Reported

Yes A pharmacist telephoned patients at their home every week for 12 weeks. Patients were questioned about when and where prescriptions were filled, how they paid for their prescriptions, potential side effects, overall well being and reasons for nonadherence when applicable.

Guthrie RM. The effects of postal and telephone reminders on compliance with pravastatin therapy in a national registry: results of the first myocardial infarction risk reduction program. Clinical Therapeutics 2001;23(6):970–80 [40].

To examine the effects of postal and telephone reminders on patient self reported adherence with pravastatin treatment

From Dec 97 to Dec 98. Community-based physicians

Yes, 4:1 Not Reported

Yes Not reported

Kalia NK, Miller LG, Nasir K, Blumenthal RS, Agrawal N, Budoff MJ. Visualizing coronary calcium is associated with improvements in adherence to statin therapy. Atherosclerosis. 2006 Apr;185(2):394-9 [41].

To assess whether visualization of coronary calcium would positively affect patients adherence rates

Patients referred by primary care to imaging center for electron beam tomography coronary calcium measurement

No Not Reported

Own control physician


12

Vrijens B, Belmans A, Matthys K, de Klerk E, Lesaffre E. Effect of intervention through a pharmaceutical care program on patient adherence with prescribed once-daily atorvastatin. Pharmacoepidemiol Drug Saf 2006;15:115-21 [42].

To estimate the effect of a pharmaceutical care program on the adherence of once-daily atorvastatin treatment in patients with elevated cholesterol levels

Flanders and Wallonia, Belgium, 2002-2002

Open label Not Reported

Yes Pharmacist

Lee JK, Grace KA, Taylor AJ. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial. JAMA 2006;296: 2563-71 [43].

To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure and low density lipoprotein cholesterol.

Walter Reed Army Medical Center, June 2004 to Aug 2006.

Yes No Yes Pharmacist

Lee SS, Cheung PY, Chow MS. Benefits of individualized counseling by the pharmacist on the treatment outcomes of hyperlipidemia in Hong Kong. J Clin Pharmacol 2004;44:632-9 [44].

To determine the effect of pharmacists individualized counseling on patients drug adherence, lowering of lipid concentrations and attainment of ATP III LDL goal.

Tsuen Wan Adventist Hospital in Hong Kong, March-June 2002.

Yes, alternates days of the week

Physicians were blinded

Yes Physician

Marquez-Contreras E, Casado-Martinez JJ, Lopez A et al. Therapeutic compliance in dyslipidemias. A trial of the efficacy of health education. Aten Primaria 1998; 22: 79–84 [45].

To assess the efficacy of health education on adherence in patients with dyslipidemias

Health Center La Orden de Huelva in Spain

Yes Not reported Yes Physician

Marquez-Contreras E, Casado Martinez JJ, Corchado AY et al. Efficacy of an intervention to improve therapy compliance in lipaemia cases. Aten Primaria 2004; 33: 15 [46].

To assess the efficacy of the intervention through a telephone call on patients adherence with lowering lipid medications

Health Center La Orden de Huelva in Spain

Yes Not Reported

Yes Not reported


13

216

Marquez-Contreras E, Casado Martines JJ, Motero Carrasco J, Martin de Pablos J, Chavez R, Losada C, Pastoriza JC. Therapy compliance in cases of hyperlipidemia, as measured through electronic monitors. Is a reminder calendar to avoid forgetfulness effective? Aten Primaria, 2007;39:661-8 [47].

To analyze the efficacy of the intervention with a calendar reminder of the medication taking in the treatment of hyperlipidemias

Spain Yes Not Reported

Yes Physician

Tamblyn R, Reidel K, Huang A, Taylor L, Winslade N, Bartlett G, Grad R, Jacques A, Dawes M, Larochelle P, Pinsonneault A. Increasing the Detection and Response to Adherence Problems with Cardiovascular Medication in Primary Care through Computerized Drug Management Systems: A Randomized Controlled Trial. Med Decis Making. 2009 [48].

To determine if a cardiovascular medication tracking and nonadherence alert system, incorporated into a computerized health record system, would increase drug profile review by primary care physicians, increase the likelihood of therapy change and improve adherence with antihypertensive and lipid lowering drugs.

Primary care practices in the Quebec Province, Canada

Yes Single blind Yes Physician

Tsuyuki RT, Olson KL, Dubyk AM, Schindel TJ, Johnson JA. Effect of community pharmacist intervention on cholesterol levels in patients at high risk of cardiovascular events: the Second Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP-plus). Am J Med. 2004 Jan 15;116(2):130-3 [49].

To assess the effect of a community pharmacist-initiated management program on cholesterol levels in patients at high risk of cardiovascular events.

Community pharmacies in six provinces in Canada, six months of follow-up

Yes Not Reported

Yes. Before-after design.

Pharmacist


14

Table 2. Characteristics of Intervention and Outcomes by Study 217 218 Reference Intervention Type Study Group Control Group Measure of adherence Clinical Outcomes: LDL-

C, HDL-C, TG, total cholesterol

Ali F, et al. Can J Clin Pharmacol 2003;10:101-6.

Patient education. Slide kit, pamphlets with information related to CV medical literature, health, lifestyle and treatment information; case report forms for patient information and formats for consultation and follow up

Counseling provided by pharmacist

Subjects own control

Prescription renewal rates and average number of days to prescription refill. Non-adherence was defined as deviation of 20% or higher from the prescribed treatment duration.

Total cholesterol, LDL, HDL and TG. Secondary outcomes were patient satisfaction and monetary value of pharmacists services

Allen JK, et al. American Heart Journal 2002;144(4):678–86.

Medication management (Case) NURS group: Case management from a nurse practitioner for one year after discharge who monitored and prescribed lipid lowering therapy. The nurse provided one outpatient visit an 4-6 weeks after discharge, and counseling for lifestyle modifications and adjustment in lipid lowering medications.

EUC: usual care provided by primary care physician or cardiologist, written results of full lipid profiles, recommendations on goal levels for lipids, diet and physical activity

Lipids profile within 6 months from the referring physician's office, and 4 weeks and 12 months after discharge. The study group also had fasting lipid profile 5-6 weeks after discharge and before intervention; dietary intake using the Block Health Habits and History questionnaire food frequency at baseline and 12 months after discharge from the hospital


15

Bozovich M, et al. Pharmacotherapy 2000;20 (11):1375–83.

Patient education, evaluation of barriers to adherence, review of other diseases or therapies that could influence lipids' management, creation of drug therapy plan, and nutrition counseling

Clinical pharmacist lead the intervention

Random selection from a list of patients from nonparticipating cardiologists practices with ICD-9 codes of CAD. They were followed by cardiologist or PCP who shared information with cardiologist.

Adherence to lipid profiles, liver function tests and medication (direct patient questioning and refills from local pharmacists)

LDL, HDL, TG, total cholesterol

Faulkner MA, et al. Pharmacotherapy 2000;20(4):410–6.

Intensified patient care. A pharmacist telephoned patients at their home every week for 12 weeks. Patients were questioned about when and where prescriptions were filled, how they paid for their prescriptions, potential side effects, overall well being and reasons for non-adherence when applicable

Telephone contact. Usual care: no telephone contact

It was measured by pill and packet counts at 6 and 12 weeks clinic visits. For long-term adherence, pharmacies at which patients filled their prescriptions were contacted at 1 and 2 years to document refills. Non adherence was defined as patients returning more than 20% of prescribed pills at 6/12 weeks visits or failing to refill 80% or more of their prescriptions at 1/2 years

Lipids profile


16

Guthrie RM. Clinical Therapeutics 2001;23(6):970–80.

Intensified patient care. Telephone reminders were sent at weeks 2 and 8, reminder postcards at week 4, 4 and 5 months

Telephone reminders. Usual care Questionnaire Not reported

Kalia NK, et al. Atherosclerosis. 2006 Apr;185(2):394-9.

patient information Patients visualizing their CAC

No Questionnaire Not reported

Vrijens B, et al. Pharmacoepidemiol Drug Saf 2006;15:115-21.

Intensified patient care. Use of Medication Electronic Monitoring System (MEMS), electronically monitored pharmaceutical package designed to compile the dosing histories of ambulatory patients taking oral medications

Supportive program. Usual care Adherence defined as the proportion of days during which the electronic device record showed that the patient had taken the daily dose. Persistence-length of time between onset and discontinuation of treatment execution, and adherence

Not reported

Lee JK, et al. JAMA 2006;296: 2563-71.

Intensified patient care Standardized medication education, regular FU by pharmacists and medication dispensed in time specific packs

Usual care Change in the proportion of pills taken vs. baseline, mean medication adherence

Changes in LDL-C and blood pressure


17

Lee SS, et al. J Clin Pharmacol 2004;44:632-9.

Intensified patient care Individualized intense counseling by physician

Usual care: routine counseling control by pharmacy staff

Interview using a questionnaire: number of missed doses. Level of adherence

% lipid reduction

Marquez-Contreras E, et al. Aten Primaria 1998; 22: 79–84.

Intensified patient care Health education followed by postal reminders

Usual care: health education

Total number of medication taken/total number of medications patient should had taken *100. Adherence=ratio between 80 and 110%.

LDL, HDL, TG, total cholesterol

Marquez-Contreras E, et al. Aten Primaria 2004; 33: 15.

Intensified patient care Health education followed by postal reminders


Proportion of adherence and Self reported, number of pills taken

LDL, HDL

Marquez-Contreras E, et al. Aten Primaria, 2007;39:661-8.

Intensified patient care Health education and calendar


Percentage of adherence

LDL, total cholesterol, HDL

Tamblyn R, et al. Med Decis Making. 2009

medication management through the use of tracking and alert system for patients

complete drug profile, refill adherence calculation and adherence alerts

Usual care: medication list alone

refills Not Reported


18

Tsuyuki RT, et al. Am J Med. 2004 Jan 15;116(2):130-3

Web-based educational module and a workshop provided by pharmacists. Pharmacists detailed the results of lipid measurements, risk factors and recommendations in special forms that were faxed to patients’ physicians. Pharmacists followed patients by telephone at week 2 and 4 after enrollment, and at the 3 and 6 months. F-U assessed adherence to recommendations, medication adherence, adverse events, drug interaction and patient education.

Patient education provided by pharmacist

Patients were their own control.

Adherence was calculated as number of units dispensed between first and last prescription/number of days between first and last prescription X number of units taken per day

Change in LDL cholesterol at baseline and after 6 months of follow-up. Proportion of patients reaching target LDL, and proportion of patients with dosage changes to their lipid-lowering medications.

219 220


19

Table 3. Characteristics of Population and Statistical Analysis by Study 221 222

Reference Population Characteristics Follow-up time

Ethics approval

Sample size

Statistical analysis

Inclusion Criteria Exclusion Criteria Potential confounders

Total Study Control

Ali F, et al. Can J Clin Pharmacol 2003;10:101-6 [36].

Non compliant patient with lipid lowering therapy detected by pharmacists in 2 refill periods; men of 45 years old and women of 55 years old, and with at least other two risk factors for CV disease.

Not Reported Not Reported Bimonthly calls for six months

Not Reported

298 149 149 Wilcoxon signed rank test. Non parametric statistics were used but they were not specified.

Allen JK, et al. American Heart Journal 2002;144(4):678–86 [37].

Adults with hypercholesterolemia and CHD who underwent coronary revascularization

Lived >75 miles from the hospital, had severe non cardiac life-threatening illness, major psychiatric or substance abuse morbidity or severe cardiac disease with poor prognosis (EF<30%), age >75 years, BMI>40, participants of another study, unable to speak or understand English or attending physician opposes patient's participation.

Yes and they included: baseline data on height, weight, blood pressure, comorbidities, disease severity, medication use at the time of admission and discharge and serum glucose levels

By a nurse practitioner in addition to their usual care or to usual care enhanced with feedback on lipids to their primary provider or cardiologist

Yes Eligible 337, 228 signed informed consent, 158 patients completed FU at 12 months (77% NURS vs 62% EUC group).

NURS=115

EUC=113

t tests, X2, multiple linear regression analysis to determine the factors that predicted LDL level at one year.


20

Bozovich M, et al. Pharmacotherapy 2000;20 (11):1375–83 [38].

Newly diagnosed patients with CHD post-PTCA, MI or bypass; history of non-adherence or history of intolerance to lipid-lowering drugs

Not Reported Some Yes, 30 min consultation with clinical pharmacists for 6 months

Not Reported

205 104 101 Mann-Whitney U Test, x2, McNemars test, Kolmogorv-Smirnov, Shapiro-Wilkes test, Wilcoxon matched pairs signed rank test

Faulkner MA, et al. Pharmacotherapy 2000;20(4):410–6 [39].

Patients who had undergone coronary artery bypass graft (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) in the previous 7-30 days were eligible. They needed to have baseline fasting LDL above 130 mg/dl, able to speak, read and understand English and have telephone at home.

Serum transaminases levels greater than two times the ULN, concomitant treatment with cyclosporine, warfarin or erythromycin, history of gastrointestinal disease including gastroesophageal reflux disease, peptic ulcer disease, Crohn's disease and ulcerative colitis.

No 6 and 12 weeks, as well as 12 and 24 months

Yes 30 15 15 Univariate anallysis. The proportion of compliant patients between groups was evaluated using X2. p value less than 0.05 was considered statistically significant


21

Guthrie RM. Clinical Therapeutics 2001;23(6):970–80 [40].

Patients with risk of first heart attack scores >=4 (scale -1 to +16) and elevated cholesterol

Previous myocardial infarction, current treatment with statin, members of Medicare or Medicaid, women of childbearing potential

Not Reported 3 months and 6 months

informed consent

13,100 10335 2765 Means and proportions, to assess differences in adherence between groups, X2 was used

Kalia NK, et al. Atherosclerosis. 2006 Apr;185(2):394-9 [41].

Asymptomatic patients on statins that were referred by primary care physician for electron beam tomography to measure their coronary calcium.

Patients who required revascularization or had stroke, MI, new onset chest pain.

Yes 43 months Not Reported

505 505 0 Univariate analysis.

Vrijens B, et al. Pharmacoepidemiol Drug Saf 2006;15:115-21 [42].

Adults who were taking atorvastatin for at least 3 months and without contraindications to continuation of treatment.

Not Reported No 12 months Yes 392 194 198 Wilcoxon rank sum test.

Lee JK, et al. JAMA 2006;296: 2563-71 [43].

Elderly taking 4 or more chronic medications daily

Patients living in assisted living or nursing home residents.

No 14 months Yes 159 83 76 t tests, x2, paired t tests, multivariate analysis.


22

Lee SS, et al. J Clin Pharmacol 2004;44:632-9 [44].

Hyperlipidemic patients who were new users of lipid lowering medications.

Psychiatric problems did not have future follow ups at the medical center or refuse to participate.

No 14 months Yes 59 31 28 Non parametric data, x2 test or fisher exact test. Two-sample ttest, p value <0.05 was considered statistically significant.

Marquez-Contreras E, et al. Aten Primaria 1998; 22: 79–84 [45].

Hypercholesterolemic patients that required pharmacological treatment, and signed informed consent

Patients that required the use of 2 or more lipid lowering medications to control lipids, hypersensitivity to statins, pregnancy, lactating women, patients with mental problems, unable to sign informed consent, or are participants of other studies.

No 4 months Yes 110 55 55 X2, t tests, statistically significant if p<0.05


23

Marquez-Contreras E, et al. Aten Primaria 2004; 33: 15 [46].

Adults with hypercholesterolemia Cardiovascular disease, individuals requiring 2 or more lipid lowering medications, contraindicated the use of statins, pregnancy, lactating women, unable to authorize participation in the study, participant of other trial or patients who lived with another patient that was taking lipid lowering medications

No 24 weeks Yes 115 56 59 X2, t student

Marquez-Contreras E, et al. Aten Primaria, 2007;39:661-8 [47].

Adults with hypercholesterolemia, signed informed consent, required lipid lowering medications

Patients that required the use of 2 or more lipid lowering medications to control lipids, hypersensitivity to statins, pregnancy, lactating women, patients with mental problems, unable to sign informed consent, or are participants of other studies.

No 24 months Yes 188 96 92 X2, ttest, McNemar test


24

Tamblyn R, et al. Med Decis Making. 2009 [48].

Primary care physicians consent patients to participate in the study, they were insured with the provincial drug insurance program and had at least one lipid lowering or antihypertensive drug prescribed in the 3 months prior to the index visit.

No 6 months Yes 2293 1166 1127 Descriptive statistics and logistic regression

Tsuyuki RT, et al. Am J Med. 2004 Jan 15;116(2):130-3 [49].

Patients with high risk of cardiovascular events: history of coronary artery disease, coronary revascularization procedures, peripheral vascular disease, or cerebrovascular disease; presence of diabetes, or a 10-year Framingham risk score >30%.

Patients with LDL <= 2.5 mmol/L (<=97 mg/dl), enrollment in another lipid-lowering study, being followed in a specialty risk reduction clinic, dosage changes or use of a new lipid-lowering medication within the previous 6 weeks, or myocardial infarction within the previous 3 months.

Not reported 6 months Yes 419 419 419 (patients

own control)

Paired t test to assess clinical endpoint. Descriptive statistics for all variables.

223 224


25

Table 4. Results and Quality Scores by Study 225 226

Reference Adherence Results Clinical Results

Loss of Follow-up

Main results Lipids levels Other relevant results

Characteristics of patients lost fo Follow Up clearly described, Yes=1, No=0

Results adjusted by confounders? Yes=1, No=0

External validity (representative of study population), Yes=1, No=0

Total Quality Score (% Quality Score)

Ali F, et al. Can J Clin Pharmacol 2003;10:101-6.

Not Reported Data available for 91/149 original patients. After the program there was an increased by 15.3% in prescription renewal dates. The average days per refill was reduced by 11 days on average

Total cholesterol was reduced by 6% post-intervention, plasma TG by 16.2% and LDL by 8.5%. No changes in HDL

99.2% were satisfied with the program and they indicated a willingness to pay at average of 34.50 +- 13.50 for 30 min of consultation

No No No 17 (57%)

Allen JK, et al. American Heart Journal 2002;144(4):678–86.

The reasons for loss to FU were: inconvenience, changed providers, unable to contact, death,

At one year, 87% of patients in the NURS group and 79% in the EUC group were on lipid lowering drugs; 97% were taking monotherapy.

Nurse spent an average of 4.5 hours total per patient for delivering the case management intervention. On average, each patient was contacted by a nurse an average of 7 times in one year intervention period. Nurse spent time counseling patients on diet, medication, exercise and smoking cessation. There were significantly changes in lipid

No No Yes No 21 (70%)


26

levels in the NURS group, as well as greater reduction in dietary consumption of calories, total fat, saturated fat and cholesterol,

Bozovich M, et al. Pharmacotherapy 2000;20 (11):1375–83.

Not reported There were not differences at baseline between study and control groups. 69% of study group reached NCEP goal at 6 months compared with 50% of control (p=0.016).

LDL decreased by 23 mg/dl in the study group vs. 20 mg/dl in the control group (NS). In the study group, 12% increased their HDL and 2% reduction of TG.

No No No No 18 (60%)

Faulkner MA, et al. Pharmacotherapy 2000;20(4):410–6.

No Short term adherence: No differences between groups and treatment. The adherence in the telephone group was 92% at 6 weeks and 88% at 12 weeks while the comparator had 90% at 6 weeks and 87% at 12 weeks. There were statistically significant differences between groups in the long-term adherence with overall

There were significant changes in total cholesterol, LDL and TG levels at short and long adherence. The reasons for non adherence included gastrointestinal disturbances, perception that the regime was inconvenient and inability to detect benefit from therapy.

Not Reported No No No 22 (73%)


27

adherence at 62% at one year and 55% at two years compared to 37% and 31% respectively

Guthrie RM. Clinical Therapeutics 2001;23(6):970–80.

No 79.7% of patients in the intervention group reported taking pravastatin as prescribed compared with 77.4% of comparator (NS). 64.3% of intervention vs. 61.8% comparator reported they missed no doses in the previous week.

Not reported Medication adherence was significantly associated with more physicians visits (97.5% vs. 82%), 62.5% compliant modified eating habits compared with 51.2% in non compliant; 38.7% lost weight compared to 34.9% of non compliant and they increased physical activity 40.7% vs. 31%.

No No 16 (53%)

Kalia NK, et al. Atherosclerosis. 2006 Apr;185(2):394-9.

Yes The adherence with statins was significantly higher from 52% in quartile 1 to 92% in fourth quartile. 44% with CAC score of zero adhered to statin therapy at baseline compared to 90% of those with CAC>400. Patients in the fourth quartile were 10 times more likely to persist with statins.

Not reported Not reported No No No 13 (43%)


28

Vrijens B, et al. Pharmacoepidemiol Drug Saf 2006;15:115-21.

No The % of adherence overall was 95% in the intervention compared to 89% in the control, at the end of the study. The intervention resulted in a 6.5% increase in post-baseline adherence driven by a 13% increase in persistence. In the intervention group 13% discontinued medications prior to 300 days compared to 26% in the control.

Not Reported Not Reported No No No 16 (53%)

Lee JK, et al. JAMA 2006;296: 2563-71.

Yes Increased adherence from 5 to 98.7%. Mean baseline medication adherence at completion of run in phase was 61.2%, after the initiation of the program, the medication adherence was 96% or higher. At the end of the study 95.5% adherence was observed in the intervention compared to 69.1% in the control (p<0.001), 97% of patients adhere to 80% to all medications in the intervention compared to 21.7% in the control.

LDL levels were 87 mg/dl in the intervention compared to 88% in the control (NS).

Not reported No No No 21 (70%)


29

Lee SS, et al. J Clin Pharmacol 2004;44:632-9.

9 patients were dropped because physician discontinued medication

The adherence was 82.1% in the intervention compared to 60.5% in the control (p<0.05). There were 76.9% compliers in the intervention compared to 41.7% in the control.

After 3 months, there was a reduction of 80 mg/dl in the intervention compared to 42mg/dl in the control in total cholesterol. The numbers for LDL in the intervention were 46mg/dl reduction compared to 25.5mg/dl in the comparator, and 86.7mg/dl reduction in TG compared to 22 mg/dl in the control. By the end of 3 months, 80.8% of the individualized group achieved the ATP III LDL goals compared with 58.3% of the control (p<0.05).


Marquez-Contreras E, et al. Aten Primaria 1998; 22: 79–84.

No The rate of adherence was 81% in the intervention compared to 61% in the control.

Only TG were statistically significant different between the groups. The percentage of patients under control was 56% for intervention compared to 46% in the control. At the end of the study, this numbers were 71% in the intervention compared to 54% in the control.


Marquez-Contreras E, et al. Aten Primaria 2004; 33: 15.

No 93.5% adhere to tx in the intervention compared to 64.4% in the control. Mean adherence was 93 in the intervention compared to 84 in the control. 43.9% patients were under control in the intervention compared to 23% in the control

There were higher reduction in the intervention group in LDL and total cholesterol, and higher HDL compared to control



30

Marquez-Contreras E, et al. Aten Primaria, 2007;39:661-8.

No Mean adherence was 92% in the intervention compared to 84% in the control.

66.7% had cholesterol under controlled in the intervention compared to 41% for the control


Tamblyn R, et al. Med Decis Making. 2009

No There was significant increase in drug profile review in the intervention compared to control group (44.5% vs. 35.5%, p<0.001). No significant changes in refill adherence after 6 months of FU.

Not Reported Not Reported No No No 19 (63%)

Tsuyuki RT, et al. Am J Med. 2004 Jan 15;116(2):130-3

Yes, 60 patients were lost during the follow-up period

Adherence at six months was 84%

Change in LDL from baseline to 6 month follow-up was -0.5 mmol/L (95%CI -0.4 to -0.6), a relative reduction of 13.4% (from 3.5 ± 0.7 mmol/L at baseline to 3.0 ± 0.9 mmol/L at 6 months, p<0.0001). At 6 months, 27% (95%CI 23%-32%) of patients achieved the target LDL cholesterol level. A total of 16% of patients started a new lipid-lowering medication, 1% had another agent added to their existing regimen, 5% changed medications, and 9% had a dosage increase.


227


31

Figure 1. Percentage of adherence increased by study (adherence results in the study 228

group minus comparator group). 229

0

10

20

30

40

50

60

70

80

90

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Study Number

% A

dh

eren

ce In

crea

sed

230 231

232


32

References

1. World Health Organization-2002. The World Health Report 2002. Reducing risks,

promoting healthy life. http://www.who.int/whr/2002/en/ accessed on March 28,

2011. Edited by the World Health Organization

2. Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in US deaths from

coronary disease, 1980-2000. NEJM 2007;356(23):2388-98

3. McDermott MM, Schmitt B, Wallner E. Impact of medication nonadherence on

coronary heart disease outcomes. Arch Intern Med, 1997;157:1921-1929

4. Osterberg L, Blaschke T. Adherence to medications. NEJM, 2005;353:487-497.

5. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ,

Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J,

Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular

events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov

20;359(21):2195-207.

6. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R,

Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive

lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26

randomised trials. Cholesterol Treatment Trialists’ (CTT) Collaboration. Lancet. 2010

Nov 13;376(9753):1670-81.

7. Mills EJ, Wu P, Chong G, Ghement I, Singh S, Akl EA, Eyawo O, Guyatt G,

Berwanger O, Briel M. Efficacy and safety of statin treatment for cardiovascular

disease: a network meta-analysis of 170,255 patients from 76 randomized

trials.QJM. 2011 Feb;104(2):109-24.

8. Avorn J, Monette J, Lacour A, et al. Persistence of use of lipid-lowering

medications: A cross-national study. JAMA 1998; 279:1458-1462.

http://www.who.int/whr/2002/en/


33

9. Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly

patients with and without acute coronary syndromes. JAMA. 2002 Jul 24-

31;288(4):462-7.

10. Grant RW, O'Leary KM, Weilburg JB, Singer DE, Meigs JB. Impact of concurrent

medication use on statin adherence and refill persistence Arch Intern Med. 2004 Nov

22;164(21):2343-8.

11. Ebrahim S. Detection, adherence and control of hypertension for prevention of

stroke: a systematic review. Health Technology Assessment, 1998;2:11.

12 Fung V, Sinclair F, Wang H, Dailey D, Hsu J, Shaber R. Patients’ perspectives

on non-adherence to statin therapy. A focus group study. The Permanente Journal,

2010; 14:4-10.

13 Wei L, MacDonald TM, Watson AD, Murphy MJ. Effectiveness of two statin

prescribing strategies with respect to adherence and cardiovascular outcomes:

observational study. Pharmacoepidemiol Drug Saf, 2007;16(4):385-392.

14 Blackburn DF, Dobson RT, Blackburn JL, Wilson TW. Cardiovascular morbidity

associated with nonadherence to statin therapy. Pharmacotherapy, 2005;25(8):1035-

1043.

15. Petrilla AA, Benner JS, Battleman DS, Tierce JC, Hazard EH. Evidence-based

interventions to improve patient compliance with antihypertensive and lipid-lowering

medications. Int J Clin Pract, 2005;59:1441-1451.

16. Guthrie RM. The effects of postal and telephone reminders on compliance with

pravastatin therapy in a National Registry. Clin Therapeutics, 2001;23:970-980.

17. Downs SH, Black N. The feasibility of creating a checklist for the assessment of

the methodological quality both of randomised and nonrandomized studies of health

care interventions. J Epidemiol Community Health 1998;52:377-84.


34

18. Salas M, Hughes D, Zuluaga A, Vardeva K, Lebmeier M. Costs of medication

nonadherence in patients with diabetes mellitus: a systematic review and critical

analysis of the literature, Value Health. 2009 Sep;12(6):915-22.

19. Wei L, MacDonald TM, Watson AD, Murphy MJ. Effectiveness of two statin

prescribing strategies with respect to adherence and cardiovascular outcomes:

observational study. Pharmacoepidemiol Drug Saf. 2007 Apr;16(4):385-92.

20. Ho PM, Magid DJ, Shetterly SM, Olson KL, Maddox TM, Peterson PN, Masoudi

FA, Rumsfeld JS. Medication nonadherence is associated with a broad range of

adverse outcomes in patients with coronary artery disease. Am Heart J. 2008

Apr;155(4):772-9.

21. Simpson RJ Jr, Mendys P. The effects of adherence and persistence on clinical

outcomes in patients treated with statins: a systematic review. J Clin Lipidol. 2010

Nov-Dec;4(6):462-71.

22. Cherry SB, Benner JS, Hussein MA, Tang SS, Nichol MB. The clinical and

economic burden of nonadherence with antihypertensive and lipid-lowering therapy

in hypertensive patients. Value Health. 2009 Jun;12(4):489-97.

23. Lardizabal JA, Deedwania PC. Benefits of statin therapy and compliance in high

risk cardiovascular patients. Vasc Health Risk Manag. 2010 Oct 5;6:843-53.

24. Yam FK, Akers WS, Ferraris VA, Smith K, Ramaiah C, Camp P, Flynn JD.

Interventions to improve guideline compliance following coronary artery bypass

grafting. Surgery. 2006 Oct;140(4):541-7

25. Jelinek M, Vale MJ, Liew D, Grigg L, Dart A, Hare DL, Best JD. The COACH

program produces sustained improvements in cardiovascular risk factors and

adherence to recommended medications-two years follow-up. Heart Lung Circ. 2009

Dec;18(6):388-92.


35

26. Brookhart MA, Patrick AR, Schneeweiss S, Avorn J, Dormuth C, Shrank W, van

Wijk BL, Cadarette SM, Canning CF, Solomon DH. Physician follow-up and provider

continuity are associated with long-term medication adherence: a study of the

dynamics of statin use. Arch Intern Med. 2007 Apr 23;167(8):847-52.

27. Gibson TB, Mark TL, McGuigan KA, Axelsen K, Wang S. The effects of

prescription drug copayments on statin adherence. Am J Manag Care. 2006

Sep;12(9):509-17.

28. Fung V, Sinclair F, Wang H, Dailey D, Hsu J, Shaber R. Patients' perspectives

on nonadherence to statin therapy: a focus-group study.Perm J. 2010

Spring;14(1):4-10.

29. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005 Aug

4;353(5):487-97.

30. Piette JD, Heisler M, Krein S, Kerr EA. The role of patient-physician trust in

moderating medication nonadherence due to cost pressures. Arch Intern Med. 2005

Aug 8-22;165(15):1749-55.

31. Peer reviewed publications. www.iadherence.org/publication.action.

32. Electronic monitoring of adherence AARDEX.

http://www.aardexgroup.com/aardex_index.php?group=aardex&id=83. Accessed on

Nov 28, 2011.

33. Freedberg KA, Hirschhorn LR, Schackman BR, Wolf LL, Martin LA, Weinstein

MC, Goldin S, Paltiel AD, Katz C, Goldie SJ, Losina E. Cost-effectiveness of an

intervention to improve adherence to antiretroviral therapy in HIV-infected patients. J

Acquir Immune Defic Syndr. 2006 Dec 1;43 Suppl 1:S113-8.

34. Charrois TL, Johnson JA, Blitz S, Tsuyuki RT. Relationship between number,

timing, and type of pharmacist interventions and patient outcomes. Charrois TL,

http://www.aardexgroup.com/aardex_index.php?group=aardex&id=83


36

Johnson JA, Blitz S, Tsuyuki RT. Am J Health Syst Pharm. 2005 Sep 1;62(17):1798-

801.

35. Tones,K. Health education, behaviour change, and the public health. Oxford

Textbook of Public Health. (Vol 3). (D. R. GS., Ed.) New York: Oxford: Oxford

University Press, 1997.

36. Ali F, Laurin MY, Lariviere C, Tremblay D, Coutier D. The effect of pharmacist

intervention and patient education on lipid-lowering medication compliance and

plasma cholesterol levels. Can J Clin Pharmacol 2003;10:101-6.

37. Allen JK, Blumenthal RS, Margolis S, Rohm YD, Miller III ER, Kelly K. Nurse

case management of hypercholesterolemia in patients with coronary heart disease:

Results of a randomized clinical trial. American Heart Journal 2002;144(4):678–86.

38. Bozovich M, Rubino CM, Edmunds J. Effect of a clinical pharmacist managed

lipid clinic on achieving National Cholesterol Education Program low-density

lipoprotein goals. Pharmacotherapy 2000;20 (11):1375–83.

39. Faulkner MA, Wadibia EC, Lucas BD, Hilleman DE. Impact of pharmacy

counseling on compliance and effectiveness of combination lipid-lowering therapy in

patients undergoing coronary artery revascularization: a randomized, controlled trial.

Pharmacotherapy 2000;20(4):410–6.

40. Guthrie RM. The effects of postal and telephone reminders on compliance with

pravastatin therapy in a national registry: results of the first myocardial infarction risk

reduction program. Clinical Therapeutics 2001;23(6):970–80.

41. Kalia NK, Miller LG, Nasir K, Blumenthal RS, Agrawal N, Budoff MJ. Visualizing

coronary calcium is associated with improvements in adherence to statin therapy.

Atherosclerosis. 2006 Apr;185(2):394-9.


37

42. Vrijens B, Belmans A, Matthys K, de Klerk E, Lesaffre E. Effect of intervention

through a pharmaceutical care program on patient adherence with prescribed once-

daily atorvastatin. Pharmacoepidemiol Drug Saf 2006;15:115-21.

43. Lee JK, Grace KA, Taylor AJ. Effect of a pharmacy care program on medication

adherence and persistence, blood pressure, and low-density lipoprotein cholesterol:

a randomized controlled trial. JAMA 2006;296: 2563-71.

44. Lee SS, Cheung PY, Chow MS. Benefits of individualized counseling by the

pharmacist on the treatment outcomes of hyperlipidemia in Hong Kong. J Clin

Pharmacol 2004;44:632-9.

45. Marquez-Contreras E, Casado-Martinez JJ, Lopez A et al. Therapeutic

compliance in dyslipidemias. A trial of the efficacy of health education. Aten Primaria

1998; 22: 79–84.

46. Marquez-Contreras E, Casado Martinez JJ, Corchado AY et al. Efficacy of an

intervention to improve therapy compliance in lipaemia cases. Aten Primaria 2004;

33: 15.

47. Marquez-Contreras E, Casado Martines JJ, Motero Carrasco J, Martin de Pablos

J, Chavez R, Losada C, Pastoriza JC. Therapy compliance in cases of

hyperlipidemia, as measured through electronic monitors. Is a reminder calendar to

avoid forgetfulness effective? Aten Primaria, 2007;39:661-8.

48. Tamblyn R, Reidel K, Huang A, Taylor L, Winslade N, Bartlett G, Grad R,

Jacques A, Dawes M, Larochelle P, Pinsonneault A. Increasing the Detection and

Response to Adherence Problems with Cardiovascular Medication in Primary Care

through Computerized Drug Management Systems: A Randomized Controlled Trial.

Med Decis Making. 2009.


38

49. Tsuyuki RT, Olson KL, Dubyk AM, Schindel TJ, Johnson JA. Effect of community

pharmacist intervention on cholesterol levels in patients at high risk of cardiovascular

events: the Second Study of Cardiovascular Risk Intervention by Pharmacists

(SCRIP-plus). Am J Med. 2004 Jan 15;116(2):130-3.

The Most Effective Patient Adherence Interventions of ... · 15 comparative group and reported...

Documents

Transcript of The Most Effective Patient Adherence Interventions of ... · 15 comparative group and reported...