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Review Article | Health Care Reform

Impact of Pharmacist Care in the Management of Cardiovascular Disease Risk Factors:  A Systematic Review and Meta-analysis of Randomized Trials FREE

Valérie Santschi, PharmD, PhD; Arnaud Chiolero, MD, MSc; Bernard Burnand, MD, MPH; April L. Colosimo, MSc, MLIS; Gilles Paradis, MD, MSc
[+] Author Affiliations

Author Affiliations: Department of Epidemiology, Biostatistics, and Occupational Health (Drs Santschi, Chiolero, and Paradis) and McGill Library, Life Sciences Library (Ms Colosimo), McGill University, Montreal, Quebec, Canada; Institute of Social and Preventive Medicine, CHUV and University of Lausanne, Lausanne, Switzerland (Drs Santschi, Chiolero, and Burnand); and Research Institute of the McGill University Health Centre, Montreal, and Institut national de santé publique du Québec, Montreal (Dr Paradis).


Arch Intern Med. 2011;171(16):1441-1453. doi:10.1001/archinternmed.2011.399.
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Background Pharmacists may improve the clinical management of major risk factors for cardiovascular disease (CVD) prevention. A systematic review was conducted to determine the impact of pharmacist care on the management of CVD risk factors among outpatients.

Methods The MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials that involved pharmacist care interventions among outpatients with CVD risk factors. Two reviewers independently abstracted data and classified pharmacists' interventions. Mean changes in blood pressure, total cholesterol, low-density lipoprotein cholesterol, and proportion of smokers were estimated using random effects models.

Results Thirty randomized controlled trials (11 765 patients) were identified. Pharmacist interventions exclusively conducted by a pharmacist or implemented in collaboration with physicians or nurses included patient educational interventions, patient-reminder systems, measurement of CVD risk factors, medication management and feedback to physician, or educational intervention to health care professionals. Pharmacist care was associated with significant reductions in systolic/diastolic blood pressure (19 studies [10 479 patients]; −8.1 mm Hg [95% confidence interval {CI}, −10.2 to −5.9]/−3.8 mm Hg [95% CI,−5.3 to −2.3]); total cholesterol (9 studies [1121 patients]; −17.4 mg/L [95% CI,−25.5 to −9.2]), low-density lipoprotein cholesterol (7 studies [924 patients]; −13.4 mg/L [95% CI,−23.0 to −3.8]), and a reduction in the risk of smoking (2 studies [196 patients]; relative risk, 0.77 [95% CI, 0.67 to 0.89]). While most studies tended to favor pharmacist care compared with usual care, a substantial heterogeneity was observed.

Conclusion Pharmacist-directed care or in collaboration with physicians or nurses improve the management of major CVD risk factors in outpatients.

Figures in this Article

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in adults worldwide1 and accounts for approximately one-third of mortality in Canada2 and in the United States.3 Randomized studies have demonstrated the efficacy of lowering blood pressure (BP) and cholesterol levels or smoking cessation to reduce CVD mortality and morbidity.4 However, control of CVD risk factors is far from optimal in the population5,6 and only a minority of patients with CVD risk factors achieved target goals for low-density lipoprotein cholesterol (LDL-C) levels7 or BP.6 Interventions to improve the management of CVD risk factors are therefore needed.

Because patients have difficulties accessing primary care physicians and health care costs are rapidly rising, greater use of community-based models of care has been proposed.8 Among these models is the greater integration of the pharmacist as a provider of health services and member of the health care team. Pharmacists are highly accessible health care professionals, and because of their knowledge of drug therapy and their computerized records of medications, they are particularly well positioned to provide the necessary medication instructions to patients to improve safe medication use and are in collaboration with primary care physicians to assist in preventive CVD care.9,10 Studies have demonstrated beneficial interventions of pharmacists in medication use,11 identification of patients at high risk of CVD,12 and CVD management.10 Interventions have included pharmacist-only or pharmacist-collaborative care as part of disease management programs, clinical pharmacy cardiac risk services,1315 and community-based programs that focus on modifiable CVD risk factors.10,16,17 Therefore, interventions delivered by pharmacists may be key to improve the management and outcomes among patients with CVD risk factors.10

Previous studies have shown that collaborative care involving pharmacists may help the management of diabetes,16 dyslipidemia,10 hypertension,18,19 heart failure,20 and CVD17 and reduces the risk of all-cause and heart failure hospitalizations.21 To more effectively use the expertise of pharmacists in CVD care, it is necessary to better understand their roles and contributions to patient care. A review of pharmacist interventions suggested that pharmacy-based interventions improve surrogate outcomes of CVD.22 However, this review was not systematic in its coverage and did not aggregate the findings through meta-analysis. Therefore, we conducted a systematic review of randomized studies to determine the impact of pharmacist care on the management of major CVD risk factors among outpatients.

DATA SOURCES AND SEARCHES

In collaboration with a medical research librarian (A.L.C.), we conducted a systematic literature search of the electronic databases MEDLINE via PubMed (1950 to November 2010), EMBASE (1980 to November 2010), CINAHL (1937 to November 2010), and the Cochrane Central Register of Controlled Trials (up to November 2010) for randomized controlled trials (RCTs). Inclusion criteria and methods of analysis were specified in advance and documented in a protocol available on request.

The PubMed search syntax served as the basis for all search strategies, using both Medical Subject Headings (MeSH) and text terms with Boolean operators (see eAppendix for the full electronic search strategy). MESH terms included cardiovascular disease-related terms (Cardiovascular Diseases, Dyslipidemias, Diabetes Mellitus, Smoking, and Overweight) and pharmacist-related terms (Pharmacists, Pharmaceutical Services, Pharmacy Service, Hospital, Pharmacies, and Pharmacy). The search was focused on RCTs using the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE. The search strategy was then adapted for EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials. In addition to these automated searches, we conducted a hand search of bibliographies of all relevant articles. We considered publications in any language.

STUDY SELECTION

Two authors (V.S. and A.C.) independently screened titles, abstracts, and full articles from the literature search to determine eligibility (Figure 1). We included studies that (1) had a randomized control design; (2) evaluated the impact of pharmacist care delivered by pharmacist, community pharmacist, hospital pharmacist, or clinical pharmacist; and (3) were conducted among adults outpatients with any modifiable CVD risk factors (hypertension, dyslipidemia, diabetes, smoking, or obesity), irrespective of whether they were receiving CVD pharmacological treatment, compared with a usual care group. Outcomes of interest for this study were systolic and diastolic BP, total cholesterol (TC), LDL-C, or smoking. Studies involving only diabetic patients were not included. Disagreements were resolved by discussion. Based on a recent systematic review on pharmacist care of patients with heart failure,21 the classification of pharmacist interventions was made using a priori–defined categories: pharmacist-directed care (pharmacist initiated and managed interventions) and pharmacist collaborative care (pharmacist collaborated in interventions conducted by a multidisciplinary health care team).

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Figure 1. Flow diagram of studies assessed and included. CVD indicates cardiovascular disease; RCT, randomized controlled trial.

DATA EXTRACTION AND RISK OF BIAS IN INCLUDED STUDIES

Data extraction was independently performed by 2 authors (V.S. and A.C.) using a standardized data collection form. From each included study, information was abstracted on the following: (1) study author, year of the publication, and country where the study was conducted; (2) study characteristics (including study setting and design, duration of follow-up and sample size); (3) characteristics of participants (including sex, age, CVD risk factors, and medications); (4) characteristics of interventions (including description and frequency of the pharmacist intervention); (5) characteristics of usual care group; and (6) types of outcome measure (including change in BP from baseline, BP at follow-up; change in LDL-C and TC levels from baseline, LDL-C and TC levels at follow-up; and prevalence of smoking cessation).

Risk of bias in the adequacy of randomization, concealment of allocation, blinding of outcome assessors, completeness of data, selective outcome reporting, and other bias (eg, important baseline imbalance in patient characteristics) was assessed by 2 authors (V.S. and A.C.) using the Cochrane Risk of Bias Tool.23 For each item, the quality characteristics of each study were rated as (1) low risk of bias; (2) unclear; and (3) high risk of bias. Disagreements between the reviewers (V.S. and A.C.) were resolved by an open dialogue to develop consensus which was reached without the involvement of a third author.

STATISTICAL ANALYSIS

Statistical analyses were conducted following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions23 and the PRISMA statement.24 Data were analyzed using STATA version 11.0 (StataCorp, College Station, Texas). Average intervention effects were calculated as relative risks with 95% confidence intervals (CIs) for dichotomous data using a random effects model. For continuous data, we used a random effects model to calculate weighted mean differences with 95% CIs. We calculated standard deviations from standard errors or 95% CIs presented in the articles if required. Heterogeneity was quantified using the I2 and the χ2 test of heterogeneity.23 Funnel plots were drawn and Egger tests were computed to explore the possibility of publication bias. To explore possible determinants of heterogeneity, we conducted post hoc subgroup analyses according to selected study characteristics. We did not perform a meta-regression, given the relatively limited number of studies. Sensitivity analyses were conducted by (1) excluding relatively small studies (with fewer than 50 participants per randomization group); (2) excluding the study by Hennesy et al,25 which was the only study in which the pharmacist did not have direct contact with patients; and (3) restricting analysis to studies of good quality.

Searches identified 11 255 potential citations. After initial screening of titles and abstracts, 154 full-text studies were assessed for eligibility and 30 RCTs, all published in the English language, met inclusion criteria (Figure 1).

DESCRIPTION OF STUDIES AND TYPES OF INTERVENTIONS

Table 1 and Table 2 summarize the characteristics of the included studies. The outcome was BP in 19 studies (10 479 patients),18,25,26,3034,36,39,4248,50,51 TC in 9 studies (1121 patients),9,28,29,35,37,38,41,49,52 LDL-C in 7 studies (924 patients)28,29,32,35,41,49,52 and smoking in 2 studies (165 patients).27,40No study reported obe-sity or overweight as outcome. Six cluster RCTs were randomized at pharmacy43 or provider care level.18,25,46,50,52 The remaining trials were randomized at patient level.9,2642,44,45,4749,51

Table Graphic Jump LocationTable 1. Characteristics of Included Studies: Study Setting and Design, Sample Size, and Study Participants
Table Graphic Jump LocationTable 2. Characteristics of Included Studies: Key Componevnts of Pharmacist Interventions, Intervention Frequency, Usual Care Group, and Outcomes

The included studies involved a total of 11 765 participants aged from 52 to 77 years and followed over a mean of 8 months (minimum, 3 months; maximum, 24 months) (Table 1 and Table 2). Overall, 54% of the participants were women. Patients had uncontrolled CVD risk factors in 17 studies and were receiving pharmacological treatment (antihypertensive or lipid-lowering drugs) in 18 studies. In the remaining studies, patients with controlled or uncontrolled CVD risk factors and with or without pharmacological treatment were included.

Most studies (n = 20) were conducted in North America. Other studies were conducted in South America (n = 3), Asia (n = 3), Europe (n = 2), and Australia (n = 2). Participants were most often followed in outpatients clinics (20 studies), eg, primary care center or family medicine clinic. Five studies were conducted in community pharmacies30,33,35,37,43 and 5 in both outpatients clinics and community pharmacies.3941,50,52 One study involved a pharmacist intervention delivered at home outside of a health care setting.38

Eighteen studies were pharmacist-directed care2643 and 12 pharmacist-collaborative care (Table 1 and Table 2).9,18,25,4452 The interventions exclusively delivered by pharmacist or implemented in collaboration with physicians or nurses included (1) educational interventions directed to patients (defined as education and counseling about medications, lifestyle or compliance; distribution or use of educational material; patient educational workshop) in 26 studies9,2527,3045,4752; (2) patient-reminder systems (defined as telephone contact; using Web site; home visit; or drug adherence aids) in 9 studies18,29,31,32,34,38,43,49,50; (3) medication management (defined as medication review from medical records or patient interview; assessment of medication compliance; monitoring of medication therapy such as assessment, adjustment, or change of medications) in 22 studies9,18,26,28,29,3133,35,38,39,41,42,4452; (4) feedback to health care professional (defined as drug-related problems (DRPs) identification; recommendation to physicians regarding medications change; meeting with team to discuss care) in 24 studies9,18,25,28,30,31,3339,41,4352; (5) measurement of CVD risk factors or reviewing of laboratory data by pharmacist during follow-up in 12 studies9,28,30,31,34,35,3840,4345; and (6) an educational intervention directed to health care professional (defined as a training program or distribution of educational material to other health care professionals including physicians) in 2 studies.25,46

METHODOLOGICAL QUALITY OF INCLUDED STUDIES

The studies were of variable methodological quality (see eFigure). Information on allocation concealment or blinding to outcome assessors was not described in most studies. None of the study blinded study participants to the pharmacist intervention. Most of the studies were free of selective outcome reporting.

OUTCOMES
Blood Pressure

The majority of the 19 studies demonstrated beneficial and statistically significant differences in systolic and diastolic BP between pharmacist and usual care groups (Figure 2). No study demonstrated a statistically significant difference in favor of the usual care group. The pooled estimate of the 19 RCTs showed a significant reduction in BP for pharmacist care compared with usual care (weighted mean difference in systolic BP, −8.1 mm Hg [95% CI, −10.2 to −5.9], P < .001; weighted mean difference in diastolic BP, −3.8 mm Hg [95% CI, −5.3 to −2.3], P < .001). A substantial heterogeneity was observed for both systolic (I2 = 75.5%) and diastolic BP (I2 = 85.3%).

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Figure 2. Forest plots of the mean difference in systolic (A) and diastolic (B) blood pressure (BP) with the pharmacist care group compared with the usual care group. CI indicates confidence interval.

TC and LDL-C

Of the 9 studies reporting TC level, 6 demonstrated a statistically significant benefit of pharmacist care (Figure 3A). Of the 7 studies reporting LDL-C level, 4 demonstrated a statistically significant benefit of pharmacist care (Figure 3B). For both outcomes no study demonstrated a statistically significant difference in favor of the usual care group. The pooled estimate showed a significant reduction in TC level (weighted mean difference, −17.4 mg/L [95% CI, −25.5 to −9.2], P < .001) and LDL-C (weighted mean difference, −13.4 mg/L [95% CI, −23.0 to −3.8], P = .006) for pharmacist care compared with usual care. A substantial heterogeneity was also observed for both TC (I2 = 78.5%) and LDL-C (I2 = 86.5%) levels.

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Figure 3. Forest plot of the mean difference in total cholesterol (TC) (A) and low-density lipoprotein cholesterol (LDL-C) (B) with the pharmacist care group compared with the usual care group. To convert LDL-C to millimoles per liter, multiply by 0.0259.

Smoking

Two studies suggested that pharmacist care helped decrease smoking (Figure 4). The pooled estimate showed a statistically significant reduction in smoking for pharmacist care compared with the usual care (relative risk, 0.77 [95% CI, 0.67 to 0.89], P = .001). No significant heterogeneity was observed.

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Figure 4. Forest plot of the relative risk of smoking with the pharmacist care group compared with the usual care group.

Subgroup Analyses

To explore the possible differences between studies and in view of the substantial heterogeneity, post hoc subgroup analyses were conducted according to the type of pharmacist care, the type and number of interventions, and the inclusion of uncontrolled or a mix of controlled and uncontrolled hypertensive patients (Table 3). These analyses were conducted for the outcome BP, for which a relatively large number of studies were available (n = 19). Pharmacist-directed care and pharmacist-collaborative care were both associated with statistical reductions in systolic and diastolic BP, but no major differences were demonstrated between the 2 types of pharmacist care (pharmacist-directed care: weighted mean difference in systolic BP, −9.1 mm Hg [95% CI, −11.7 to −6.4]; weighted mean difference in diastolic BP, −5.1 mm Hg [95% CI, −7.0 to −3.1]; and pharmacist-collaborative care: weighted mean difference in systolic BP, −6.8 mm Hg [95% CI, −9.7 to −3.9]; and weighted mean difference in diastolic BP, −2.2 mm Hg [95% CI, − 4.6 to −0.2]) (Table 3). Moreover, there were no major differences in BP reductions according to the type or the number of interventions or to the control of BP.

Table Graphic Jump LocationTable 3. Subgroup Analyses for the Difference in Systolic and Diastolic BP With Pharmacist Care Compared With Usual Care Group According to Selected Study Characteristics
Publication Bias

We explored the possibility of publication bias for studies in which the outcome was BP (n = 19). For both systolic and diastolic BP, asymmetry in the funnel plots was observed and an Egger test result was statistically significant, indicating a potential publication bias.

Sensitivity Analyses

Because of potential publication bias, a first sensitivity analysis was performed to explore the influence of relatively small studies (with fewer than 50 participants per randomization group; n = 7).30,33,34,42,44,47,50 After exclusion of these studies from the meta-analysis, a similar reduction in BP for pharmacist care compared with usual care group was observed (systolic BP mean difference, −7.3 mm Hg [95% CI, −9.6 to −5.0], I2 = 78.5%; diastolic BP mean difference, −2.5 mm Hg [95% CI, −3.8 to −1.2], I2 = 80.3%).

The second sensitivity analysis was performed to assess the influence of the study by Hennessy et al,25 which was the only study in which the pharmacist had no direct contact with patients. After exclusion of this study from the meta-analysis, a similar reduction in BP for the pharmacist care group compared with the usual care group was observed (sys tolic BP mean difference, −8.3 mm Hg [95% CI, −10.1 to −6.5], I2 = 41.9%; diastolic BP mean difference, −4.0 mm Hg [95% CI, −5.5 to −2.6], I2 = 72.7%).

To explore the impact of study quality on the effect estimates, a third sensitivity analysis was conducted restricting analysis to studies of good quality. A study was of “good quality” if it had a low risk of bias on 3 items or more (of 6) using the Cochrane Risk of Bias Tool.23 Of 19 studies with the BP outcome, 818,31,35,43,44,46,48,49 (assessing 1955 participants) were of good quality and showed similar significant reductions in BP for the pharmacist care group compared with the usual care group (systolic BP mean difference, −7.8 mm Hg [95% CI, −9.6 to −6.0], I2 = 6.5%; diastolic BP mean difference, −3.8 mm Hg [95% CI, −5.3 to −2.3], I2 = 64.4%).

Our systematic review, identifying 30 RCTs that assessed 11 765 outpatients, supports the benefit of pharmacist care interventions in the management of major CVD risk factors among outpatients. Pharmacist interventions achieved greater reductions in systolic and diastolic BP, TC, and LDL-C, and in the risk of smoking compared with the usual care group. The most frequent interventions, exclusively provided by pharmacists or implemented in collaboration with physicians or nurses, were (1) educational interventions for patients (education and counseling about medications, lifestyle, or compliance); (2) feedback to physician (DRPs identification, recommendation to physician regarding medications), and (3) medication management (medication review from medical records and monitoring of drug therapy such as adjustment or change of medications).

Our results underscore the significant benefits of pharmacist interventions in CVD risk factors and are in line with those of a previous narrative review, which suggested that pharmacist-led interventions were associated with a better control of some CVD risk factors (hypertension and dyslipidemia) in outpatients.22 Furthermore, our findings are supported by a recent systematic review53 evaluating the effect of pharmacist as team members on patient care. In this review, Chisholm-Burns et al53 reported a mean difference between the pharmacist group and the comparison group of −6.3 mg/dL (95% CI, −6.5 to −6.0) in LDL-C, −7.8 mm Hg (95% CI, −9.7 to −5.8) in systolic BP, and −2.9 mm Hg (95% CI, −3.8 to −2.0) in diastolic BP. Nevertheless, this review was restricted to studies conducted in the United States and evaluated only interventions of pharmacist as a team member, ie, pharmacist-collaborative care interventions. Furthermore, no sensitivity analyses were conducted in this review.

Pharmacist interventions varied among the identified studies and possibly included several cointerventions. Therefore, it was difficult to clearly delineate the different types of interventions, making it difficult to precisely identify which intervention was more efficient to help the management of CVD risk factors among outpatients. Our analyses that were restricted to studies assessing BP, the most frequently reported outcome, did not allow us to identify which intervention was more efficient to decrease BP. A systematic review of pharmacist care among patients with heart failure suggested that pharmacist interventions implemented in collaboration with physicians or nurses were more efficient to reduce the rate of hospitalizations compared with interventions exclusively provided by pharmacists.21 Nevertheless, our review did not show better outcomes in favor of pharmacist interventions exclusively provided by pharmacists or in favor of pharmacist interventions implemented in collaboration with physicians or nurses. Therefore, further studies are needed to define and evaluate which pharmacist interventions are the most effective for the management of CVD risk factors in different health care system organizations or jurisdictions.

The traditional view of the pharmacist's role in primary care is medication distribution. Although this role remains an important part of the activity of a pharmacist, evidence documented in our systematic review and previous reviews21,53 demonstrates a transformation of pharmacy practice toward a more clinical, patient-centered role and a collaborative approach toward pharmacist-physician in patient care. The enhanced role of the pharmacist as member of CVD health care is more successfully implemented and accepted in North America health care system compared with the European health care system. Indeed, most studies9,18,25,2729,3136,4246,48,51,52 identified in our review were conducted in North America and only 2 studies30,50 were conducted in Europe.

Our review has some limitations. First, although we conducted a rigorous and systematic review, we did not search for unindexed and unpublished literature. Our analyses indicate a potential publication bias that suggests that studies reporting favorable results of pharmacist interventions were more likely published than those reporting negative results.23 Consequently, the average estimates of the effect of pharmacist interventions may be overestimated. However, our sensitivity analysis, which excluded relatively small studies, showed that the estimate of the effect of pharmacist interventions on BP was similar to the analysis including all studies. Second, while most studies favored pharmacist care compared with usual care, a substantial heterogeneity was observed in the effect of pharmacists' interventions on BP, TC, and LDL-C, which suggests a large variation in the effect of pharmacist interventions.53 As we expected heterogeneity, we used random effects analysis to allow for differences in the treatment effect from study to study.54 Differences in terms of interventions and setting, disease severity of patients or cointerventions may explain this heterogeneity. We explored the potential sources of heterogeneity by conducting subgroup analyses by the type of pharmacist care and the type of pharmacist interventions. We found no difference in effect on BP according to the type of pharmacist care and the type of interventions. Moreover, sensitivity analyses accounting for study quality and study size reported similar effects on BP. We also investigated whether differences were observed between studies including uncontrolled or a mix of controlled and uncontrolled hypertensive patients but found no major differences. Other potential causes of heterogeneity could be comorbidities, number of medications, or age of the patients but would have required individual level data to be identified.55

Despite these limitations, our review had unique strengths. Our review was conducted following the Cochrane Handbook for Systematic Reviews of Interventions23 and the PRISMA statement.24 Our review was systematic in its coverage; considered major modifiable CVD risk factors, such as hypertension, dyslipidemia, and smoking; and included studies assessing the effect of pharmacist-directed care as well as pharmacist-collaborative care.

In conclusion, our results support the beneficial role of pharmacist care in the management of CVD risk factors among outpatients. Given the difficulties in accessing primary care physicians, the integration of pharmacist in the care of outpatients should be considered as a valuable solution for improving the management of CVD risk factors. Further studies are needed to identify which type of pharmacist interventions are best suited to help manage CVD risk factors and how this type of pharmacist care could be enhanced in various health care systems.

Correspondence: Valérie Santschi, PharmD, PhD, Institute of Social and Preventive Medicine, Rue du Bugnon 17, 1005 Lausanne, Switzerland (valerie.santschi@gmail.com).

Accepted for Publication: May 16, 2011.

Author Contributions: Drs Santschi and Chiolero had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Santschi, Chiolero, Burnand, and Paradis. Acquisition of data: Santschi, Chiolero, and Colosimo. Analysis and interpretation of data: Santschi, Chiolero, Burnand, and Paradis. Drafting of the manuscript: Santschi and Chiolero. Critical revision of the manuscript for important intellectual content: Santschi, Chiolero, Burnand, Colosimo, and Paradis. Statistical analysis: Santschi, and Chiolero. Obtained funding: Paradis. Administrative, technical, and material support: Santschi, Chiolero, and Paradis. Study supervision: Burnand and Paradis.

Financial Disclosure: None reported.

Funding/Support: This study was supported in part by the Canadian Institutes of Health Research (CIHR) Applied Public Health Research Chair in Chronic Disease Prevention to Paradis.

Previous Presentation: This study was presented as a poster at the North American Congress of Epidemiology; June 22, 2011; Montreal, Quebec, Canada.

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Gattis WA, Hasselblad V, Whellan DJ, O’Connor CM. Reduction in heart failure events by the addition of a clinical pharmacist to the heart failure management team: results of the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) Study.  Arch Intern Med. 1999;159(16):1939-1945
PubMed   |  Link to Article
Koshman SL, Charrois TL, Simpson SH, McAlister FA, Tsuyuki RT. Pharmacist care of patients with heart failure: a systematic review of randomized trials.  Arch Intern Med. 2008;168(7):687-694
PubMed   |  Link to Article
McConnell KJ, Denham AM, Olson KL. Pharmacist-led interventions for the management of cardiovascular disease—opportunities and obstacles.  Dis Manag Health Outcomes. 2008;16(3):131-144
Link to Article
Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Chichester, West Sussex; Hoboken NJ: Wiley-Blackwell; 2008
Liberati A, Altman DG, Tetzlaff J,  et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.  PLoS Med. 2009;6(7):e1000100
PubMed   |  Link to Article
Hennessy S, Leonard CE, Yang W,  et al.  Effectiveness of a two-part educational intervention to improve hypertension control: a cluster-randomized trial.  Pharmacotherapy. 2006;26(9):1342-1347
PubMed   |  Link to Article
Chiu CC, Wu SS, Lee PY, Huang YC, Tan TY, Chang KC. Control of modifiable risk factors in ischemic stroke outpatients by pharmacist intervention: an equal allocation stratified randomized study.  J Clin Pharm Ther. 2008;33(5):529-535
PubMed   |  Link to Article
Dent LA, Harris KJ, Noonan CW. Randomized trial assessing the effectiveness of a pharmacist-delivered program for smoking cessation.  Ann Pharmacother. 2009;43(2):194-201
PubMed
Ellis SL, Carter BL, Malone DC,  et al.  Clinical and economic impact of ambulatory care clinical pharmacists in management of dyslipidemia in older adults: the IMPROVE study: Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers.  Pharmacotherapy. 2000;20(12):1508-1516
PubMed   |  Link to Article
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):410-416
PubMed   |  Link to Article
Garção JA, Cabrita J. Evaluation of a pharmaceutical care program for hypertensive patients in rural Portugal.  J Am Pharm Assoc (Wash). 2002;42(6):858-864
PubMed
Green BB, Cook AJ, Ralston JD,  et al.  Effectiveness of home blood pressure monitoring, Web communication, and pharmacist care on hypertension control: a randomized controlled trial.  JAMA. 2008;299(24):2857-2867
PubMed   |  Link to Article
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(21):2563-2571
PubMed   |  Link to Article
McKenney JM, Slining JM, Henderson HR, Devins D, Barr M. The effect of clinical pharmacy services on patients with essential hypertension.  Circulation. 1973;48(5):1104-1111
PubMed
Mehos BM, Saseen JJ, MacLaughlin EJ. Effect of pharmacist intervention and initiation of home blood pressure monitoring in patients with uncontrolled hypertension.  Pharmacotherapy. 2000;20(11):1384-1389
PubMed   |  Link to Article
McMillan Nola K, Gourley DR, Portner TS,  et al.  Clinical and humanistic outcomes of a lipid management program in the community pharmacy setting.  J Am Pharm Assoc (Wash). 2000;40(2):166-173
PubMed
Okamoto MP, Nakahiro RK. Pharmacoeconomic evaluation of a pharmacist-managed hypertension clinic.  Pharmacotherapy. 2001;21(11):1337-1344
PubMed   |  Link to Article
Paulós CP, Nygren CE, Celedón C, Cárcamo CA. Impact of a pharmaceutical care program in a community pharmacy on patients with dyslipidemia.  Ann Pharmacother. 2005;39(5):939-943
PubMed   |  Link to Article
Peterson GM, Fitzmaurice KD, Naunton M, Vial JH, Stewart K, Krum H. Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy.  J Clin Pharm Ther. 2004;29(1):23-30
PubMed   |  Link to Article
Sookaneknun P, Richards RM, Sanguansermsri J, Teerasut C. Pharmacist involvement in primary care improves hypertensive patient clinical outcomes.  Ann Pharmacother. 2004;38(12):2023-2028
PubMed   |  Link to Article
Vial RJ, Jones TE, Ruffin RE, Gilbert AL. Smoking cessation program using nicotine patches linking hospital to the community.  J Pharm Pract Res. 2002;32(1):57-62
Villa LA, Von Chrismar AM, Oyarzun C, Eujenin P, Fernandez ME, Quezada M. Pharmaceutical Care Program for dyslipidemic patients at three primary health care centers: impacts and outcomes.  Latin Am J Pharm. 2009;28(3):415-420
Vivian EM. Improving blood pressure control in a pharmacist-managed hypertension clinic.  Pharmacotherapy. 2002;22(12):1533-1540
PubMed   |  Link to Article
Zillich AJ, Sutherland JM, Kumbera PA, Carter BL. Hypertension outcomes through blood pressure monitoring and evaluation by pharmacists (HOME study).  J Gen Intern Med. 2005;20(12):1091-1096
PubMed   |  Link to Article
Bogden PE, Abbott RD, Williamson P, Onopa JK, Koontz LM. Comparing standard care with a physician and pharmacist team approach for uncontrolled hypertension.  J Gen Intern Med. 1998;13(11):740-745
PubMed   |  Link to Article
Borenstein JE, Graber G, Saltiel E,  et al.  Physician-pharmacist comanagement of hypertension: a randomized, comparative trial.  Pharmacotherapy. 2003;23(2):209-216
PubMed   |  Link to Article
Carter BL, Ardery G, Dawson JD,  et al.  Physician and pharmacist collaboration to improve blood pressure control.  Arch Intern Med. 2009;169(21):1996-2002
PubMed   |  Link to Article
de Castro MS, Fuchs FD, Santos MC,  et al.  Pharmaceutical care program for patients with uncontrolled hypertension: report of a double-blind clinical trial with ambulatory blood pressure monitoring.  Am J Hypertens. 2006;19(5):528-533
PubMed   |  Link to Article
Hunt JS, Siemienczuk J, Pape G,  et al.  A randomized controlled trial of team-based care: impact of physician-pharmacist collaboration on uncontrolled hypertension.  J Gen Intern Med. 2008;23(12):1966-1972
PubMed   |  Link to Article
Lee VW, Fan CS, Li AW, Chau AC. Clinical impact of a pharmacist-physician co-managed programme on hyperlipidaemia management in Hong Kong.  J Clin Pharm Ther. 2009;34(4):407-414
PubMed   |  Link to Article
Santschi V, Rodondi N, Bugnon O, Burnier M. Impact of electronic monitoring of drug adherence on blood pressure control in primary care: a cluster 12-month randomised controlled study.  Eur J Intern Med. 2008;19(6):427-434
PubMed   |  Link to Article
Solomon DK, Portner TS, Bass GE,  et al.  Clinical and economic outcomes in the hypertension and COPD arms of a multicenter outcomes study.  J Am Pharm Assoc (Wash). 1998;38(5):574-585
PubMed
Villeneuve J, Genest J, Blais L,  et al.  A cluster randomized controlled trial to evaluate an ambulatory primary care management program for patients with dyslipidemia: the TEAM study.  CMAJ. 2010;182(5):447-455
PubMed   |  Link to Article
Chisholm-Burns MA, Kim Lee J, Spivey CA,  et al.  US pharmacists' effect as team members on patient care: systematic review and meta-analyses.  Med Care. 2010;48(10):923-933
PubMed   |  Link to Article
Riley RD, Higgins JP, Deeks JJ. Interpretation of random effects meta-analyses.  BMJ. 2011;342:d549
PubMed   |  Link to Article
Thompson SG. Why sources of heterogeneity in meta-analysis should be investigated.  BMJ. 1994;309(6965):1351-1355
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Flow diagram of studies assessed and included. CVD indicates cardiovascular disease; RCT, randomized controlled trial.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Forest plots of the mean difference in systolic (A) and diastolic (B) blood pressure (BP) with the pharmacist care group compared with the usual care group. CI indicates confidence interval.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 3. Forest plot of the mean difference in total cholesterol (TC) (A) and low-density lipoprotein cholesterol (LDL-C) (B) with the pharmacist care group compared with the usual care group. To convert LDL-C to millimoles per liter, multiply by 0.0259.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 4. Forest plot of the relative risk of smoking with the pharmacist care group compared with the usual care group.

Tables

Table Graphic Jump LocationTable 1. Characteristics of Included Studies: Study Setting and Design, Sample Size, and Study Participants
Table Graphic Jump LocationTable 2. Characteristics of Included Studies: Key Componevnts of Pharmacist Interventions, Intervention Frequency, Usual Care Group, and Outcomes
Table Graphic Jump LocationTable 3. Subgroup Analyses for the Difference in Systolic and Diastolic BP With Pharmacist Care Compared With Usual Care Group According to Selected Study Characteristics

References

Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data.  Lancet. 2006;367(9524):1747-1757
PubMed   |  Link to Article
Heart and Stroke Foundation of Canada.  The changing face of heart disease and stroke in Canada 2000. Ottawa, Canada: Laboratory Centre for Disease Control, Health Canada, Statistics Canada, Canada Institute for Health Information, Canadian Cardiovascular Society, Canadian Stroke Society, Heart Stroke Foundation of Canada; 1999. http://dsp-psd.pwgsc.gc.ca/Collection/H88-3-30-2001/pdfs/age/face_e.pdf. Accessed July 11, 2011
Lloyd-Jones D, Adams RJ, Brown TM,  et al; Writing Group Members; American Heart Association Statistics Committee and Stroke Statistics Subcommittee.  Heart disease and stroke statistics—2010 update: a report from the American Heart Association.  Circulation. 2010;121(7):e46-e215
PubMed   |  Link to Article
Forrester JS, Merz CN, Bush TL,  et al.  27th Bethesda Conference: matching the intensity of risk factor management with the hazard for coronary disease events: Task Force 4: efficacy of risk factor management.  J Am Coll Cardiol. 1996;27(5):991-1006
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Bhatt DL, Steg PG, Ohman EM,  et al; REACH Registry Investigators.  International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis.  JAMA. 2006;295(2):180-189
PubMed   |  Link to Article
Wolf-Maier K, Cooper RS, Kramer H,  et al.  Hypertension treatment and control in five European countries, Canada, and the United States.  Hypertension. 2004;43(1):10-17
PubMed   |  Link to Article
Pearson TA, Laurora I, Chu H, Kafonek S. The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals.  Arch Intern Med. 2000;160(4):459-467
PubMed   |  Link to Article
Dobson RT, Taylor JG, Henry CJ,  et al.  Taking the lead: community pharmacists' perception of their role potential within the primary care team.  Res Social Adm Pharm. 2009;5(4):327-336
PubMed   |  Link to Article
Bogden PE, Koontz LM, Williamson P, Abbott RD. The physician and pharmacist team: an effective approach to cholesterol reduction.  J Gen Intern Med. 1997;12(3):158-164
PubMed
Tsuyuki RT, Johnson JA, Teo KK,  et al.  A randomized trial of the effect of community pharmacist intervention on cholesterol risk management: the Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP).  Arch Intern Med. 2002;162(10):1149-1155
PubMed   |  Link to Article
Murray MD, Ritchey ME, Wu J, Tu W. Effect of a pharmacist on adverse drug events and medication errors in outpatients with cardiovascular disease.  Arch Intern Med. 2009;169(8):757-763
PubMed   |  Link to Article
Gardner SF, Skelton DR, Rollins SD, Hastings JK. Community pharmacy data bases to identify patients at high risk for hypercholesterolemia.  Pharmacotherapy. 1995;15(3):292-296
PubMed
Koren MJ, Hunninghake DB.ALLIANCE Investigators.  Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study.  J Am Coll Cardiol. 2004;44(9):1772-1779
PubMed
Olson KL, Rasmussen J, Sandhoff BG, Merenich JA.Clinical Pharmacy Cardiac Risk Service Study Group.  Lipid management in patients with coronary artery disease by a clinical pharmacy service in a group model health maintenance organization.  Arch Intern Med. 2005;165(1):49-54
PubMed   |  Link to Article
Pearson GJ, Olson KL, Panich NE,  et al.  Maintenance of improved lipid levels following attendance at a cardiovascular risk reduction clinic: a 10-year experience.  Vasc Health Risk Manag. 2008;4(5):1127-1135
PubMed
Rothman RL, Malone R, Bryant B,  et al.  A randomized trial of a primary care-based disease management program to improve cardiovascular risk factors and glycated hemoglobin levels in patients with diabetes.  Am J Med. 2005;118(3):276-284
PubMed   |  Link to Article
Taveira TH, Wu WC, Martin OJ, Schleinitz MD, Friedmann P, Sharma SC. Pharmacist-led cardiac risk reduction model.  Prev Cardiol. 2006;9(4):202-208
PubMed   |  Link to Article
Carter BL, Bergus GR, Dawson JD,  et al.  A cluster randomized trial to evaluate physician/pharmacist collaboration to improve blood pressure control.  J Clin Hypertens (Greenwich). 2008;10(4):260-271
PubMed   |  Link to Article
McLean DL, McAlister FA, Johnson JA,  et al; SCRIP-HTN Investigators.  A randomized trial of the effect of community pharmacist and nurse care on improving blood pressure management in patients with diabetes mellitus: study of cardiovascular risk intervention by pharmacists-hypertension (SCRIP-HTN).  Arch Intern Med. 2008;168(21):2355-2361
PubMed   |  Link to Article
Gattis WA, Hasselblad V, Whellan DJ, O’Connor CM. Reduction in heart failure events by the addition of a clinical pharmacist to the heart failure management team: results of the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) Study.  Arch Intern Med. 1999;159(16):1939-1945
PubMed   |  Link to Article
Koshman SL, Charrois TL, Simpson SH, McAlister FA, Tsuyuki RT. Pharmacist care of patients with heart failure: a systematic review of randomized trials.  Arch Intern Med. 2008;168(7):687-694
PubMed   |  Link to Article
McConnell KJ, Denham AM, Olson KL. Pharmacist-led interventions for the management of cardiovascular disease—opportunities and obstacles.  Dis Manag Health Outcomes. 2008;16(3):131-144
Link to Article
Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Chichester, West Sussex; Hoboken NJ: Wiley-Blackwell; 2008
Liberati A, Altman DG, Tetzlaff J,  et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.  PLoS Med. 2009;6(7):e1000100
PubMed   |  Link to Article
Hennessy S, Leonard CE, Yang W,  et al.  Effectiveness of a two-part educational intervention to improve hypertension control: a cluster-randomized trial.  Pharmacotherapy. 2006;26(9):1342-1347
PubMed   |  Link to Article
Chiu CC, Wu SS, Lee PY, Huang YC, Tan TY, Chang KC. Control of modifiable risk factors in ischemic stroke outpatients by pharmacist intervention: an equal allocation stratified randomized study.  J Clin Pharm Ther. 2008;33(5):529-535
PubMed   |  Link to Article
Dent LA, Harris KJ, Noonan CW. Randomized trial assessing the effectiveness of a pharmacist-delivered program for smoking cessation.  Ann Pharmacother. 2009;43(2):194-201
PubMed
Ellis SL, Carter BL, Malone DC,  et al.  Clinical and economic impact of ambulatory care clinical pharmacists in management of dyslipidemia in older adults: the IMPROVE study: Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers.  Pharmacotherapy. 2000;20(12):1508-1516
PubMed   |  Link to Article
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):410-416
PubMed   |  Link to Article
Garção JA, Cabrita J. Evaluation of a pharmaceutical care program for hypertensive patients in rural Portugal.  J Am Pharm Assoc (Wash). 2002;42(6):858-864
PubMed
Green BB, Cook AJ, Ralston JD,  et al.  Effectiveness of home blood pressure monitoring, Web communication, and pharmacist care on hypertension control: a randomized controlled trial.  JAMA. 2008;299(24):2857-2867
PubMed   |  Link to Article
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(21):2563-2571
PubMed   |  Link to Article
McKenney JM, Slining JM, Henderson HR, Devins D, Barr M. The effect of clinical pharmacy services on patients with essential hypertension.  Circulation. 1973;48(5):1104-1111
PubMed
Mehos BM, Saseen JJ, MacLaughlin EJ. Effect of pharmacist intervention and initiation of home blood pressure monitoring in patients with uncontrolled hypertension.  Pharmacotherapy. 2000;20(11):1384-1389
PubMed   |  Link to Article
McMillan Nola K, Gourley DR, Portner TS,  et al.  Clinical and humanistic outcomes of a lipid management program in the community pharmacy setting.  J Am Pharm Assoc (Wash). 2000;40(2):166-173
PubMed
Okamoto MP, Nakahiro RK. Pharmacoeconomic evaluation of a pharmacist-managed hypertension clinic.  Pharmacotherapy. 2001;21(11):1337-1344
PubMed   |  Link to Article
Paulós CP, Nygren CE, Celedón C, Cárcamo CA. Impact of a pharmaceutical care program in a community pharmacy on patients with dyslipidemia.  Ann Pharmacother. 2005;39(5):939-943
PubMed   |  Link to Article
Peterson GM, Fitzmaurice KD, Naunton M, Vial JH, Stewart K, Krum H. Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy.  J Clin Pharm Ther. 2004;29(1):23-30
PubMed   |  Link to Article
Sookaneknun P, Richards RM, Sanguansermsri J, Teerasut C. Pharmacist involvement in primary care improves hypertensive patient clinical outcomes.  Ann Pharmacother. 2004;38(12):2023-2028
PubMed   |  Link to Article
Vial RJ, Jones TE, Ruffin RE, Gilbert AL. Smoking cessation program using nicotine patches linking hospital to the community.  J Pharm Pract Res. 2002;32(1):57-62
Villa LA, Von Chrismar AM, Oyarzun C, Eujenin P, Fernandez ME, Quezada M. Pharmaceutical Care Program for dyslipidemic patients at three primary health care centers: impacts and outcomes.  Latin Am J Pharm. 2009;28(3):415-420
Vivian EM. Improving blood pressure control in a pharmacist-managed hypertension clinic.  Pharmacotherapy. 2002;22(12):1533-1540
PubMed   |  Link to Article
Zillich AJ, Sutherland JM, Kumbera PA, Carter BL. Hypertension outcomes through blood pressure monitoring and evaluation by pharmacists (HOME study).  J Gen Intern Med. 2005;20(12):1091-1096
PubMed   |  Link to Article
Bogden PE, Abbott RD, Williamson P, Onopa JK, Koontz LM. Comparing standard care with a physician and pharmacist team approach for uncontrolled hypertension.  J Gen Intern Med. 1998;13(11):740-745
PubMed   |  Link to Article
Borenstein JE, Graber G, Saltiel E,  et al.  Physician-pharmacist comanagement of hypertension: a randomized, comparative trial.  Pharmacotherapy. 2003;23(2):209-216
PubMed   |  Link to Article
Carter BL, Ardery G, Dawson JD,  et al.  Physician and pharmacist collaboration to improve blood pressure control.  Arch Intern Med. 2009;169(21):1996-2002
PubMed   |  Link to Article
de Castro MS, Fuchs FD, Santos MC,  et al.  Pharmaceutical care program for patients with uncontrolled hypertension: report of a double-blind clinical trial with ambulatory blood pressure monitoring.  Am J Hypertens. 2006;19(5):528-533
PubMed   |  Link to Article
Hunt JS, Siemienczuk J, Pape G,  et al.  A randomized controlled trial of team-based care: impact of physician-pharmacist collaboration on uncontrolled hypertension.  J Gen Intern Med. 2008;23(12):1966-1972
PubMed   |  Link to Article
Lee VW, Fan CS, Li AW, Chau AC. Clinical impact of a pharmacist-physician co-managed programme on hyperlipidaemia management in Hong Kong.  J Clin Pharm Ther. 2009;34(4):407-414
PubMed   |  Link to Article
Santschi V, Rodondi N, Bugnon O, Burnier M. Impact of electronic monitoring of drug adherence on blood pressure control in primary care: a cluster 12-month randomised controlled study.  Eur J Intern Med. 2008;19(6):427-434
PubMed   |  Link to Article
Solomon DK, Portner TS, Bass GE,  et al.  Clinical and economic outcomes in the hypertension and COPD arms of a multicenter outcomes study.  J Am Pharm Assoc (Wash). 1998;38(5):574-585
PubMed
Villeneuve J, Genest J, Blais L,  et al.  A cluster randomized controlled trial to evaluate an ambulatory primary care management program for patients with dyslipidemia: the TEAM study.  CMAJ. 2010;182(5):447-455
PubMed   |  Link to Article
Chisholm-Burns MA, Kim Lee J, Spivey CA,  et al.  US pharmacists' effect as team members on patient care: systematic review and meta-analyses.  Med Care. 2010;48(10):923-933
PubMed   |  Link to Article
Riley RD, Higgins JP, Deeks JJ. Interpretation of random effects meta-analyses.  BMJ. 2011;342:d549
PubMed   |  Link to Article
Thompson SG. Why sources of heterogeneity in meta-analysis should be investigated.  BMJ. 1994;309(6965):1351-1355
PubMed   |  Link to Article

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