Author + information
- Received February 29, 2016
- Revision received March 24, 2016
- Accepted March 25, 2016
- Published online June 21, 2016.
- Ross T. Tsuyuki, PharmD, MSca,b,∗ (, )
- Yazid N. Al Hamarneh, PhDa,b,
- Charlotte A. Jones, MD, PhDc and
- Brenda R. Hemmelgarn, MD, PhDd
- aEPICORE Centre, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
- bMazankowski Alberta Heart Institute, Edmonton, Alberta, Canada
- cSouthern Medical Program, University of British Columbia, Kelowna, British Columbia, Canada
- dDepartment of Community Health Sciences and Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- ↵∗Reprint requests and correspondence:
Dr. Ross T. Tsuyuki, Division of Cardiology, Faculty of Medicine and Dentistry, University of Alberta, EPICORE Centre, 4-000 Research Transition Facility, Edmonton, Alberta T6G 2V2, Canada.
Background Despite the cardiovascular disease (CVD) risk associated with hypertension, diabetes, dyslipidemia, and smoking, these risk factors remain poorly identified and controlled.
Objectives The study sought to evaluate the effectiveness of a community pharmacy-based case finding and intervention on cardiovascular risk.
Methods The RxEACH (Alberta Vascular Risk Reduction Community Pharmacy Project) study was a randomized trial conducted in 56 community pharmacies. Participants were recruited by their pharmacist, who enrolled adults at high risk for CVD. Patients were randomized to usual care (usual pharmacist care with no specific intervention) or intervention, comprising a Medication Therapy Management review from their pharmacist and CVD risk assessment and education. Pharmacists prescribed medications and ordered laboratory tests as per their scope of practice to achieve treatment targets. Subjects received monthly follow-up visits for 3 months. The primary outcome was difference in change in estimated CVD risk between groups at 3 months. CVD risk was estimated using the greater of the Framingham, International, or United Kingdom Prospective Diabetes Study risk scores.
Results We enrolled 723 patients (mean 62 years of age; 58% male, and 27% smokers). After adjusting for baseline values and center effect, there was a 21% difference in change in risk for CVD events (p < 0.001) between the intervention and usual care groups. The intervention group had greater improvements in low-density lipoprotein cholesterol (–0.2 mmol/l; p < 0.001), systolic blood pressure (–9.37 mm Hg; p < 0.001), glycosylated hemoglobin (–0.92%; p < 0.001), and smoking cessation (20.2%; p = 0.002).
Conclusions The RxEACH study was the first large randomized trial of CVD risk reduction by community pharmacists, demonstrating a significant reduction in risk for CVD events. Engagement of community pharmacists with an expanded scope of practice could have significant public health implications. (The Alberta Vascular Risk Reduction Community Pharmacy Project: RxEACH [RxEACH]; NCT01979471)
Cardiovascular disease (CVD) is the leading cause of death worldwide, accounting for nearly one-third of all deaths (1). Most CVDs are caused by modifiable risk factors, including tobacco smoking, hypertension, dyslipidemia, diabetes, physical inactivity, high-fat diet, and obesity (1).
Despite reductions in rates over the last few decades, CVD remains one of the leading causes of death in Canada and the United States (2,3). CVD also carries a huge financial burden, estimated at $444 billion in the United States, divided between loss of productivity and health care costs (4).
Notwithstanding major advances in treatment, the prevalence of poorly controlled CVD risk factors is still substantial in North America (5–7). Recent studies have indicated that almost 50% of the community-dwelling patients with type 2 diabetes are not at their glycosylated hemoglobin (HbA1c) (8) or cholesterol (9,10) targets, and between 50% and 62% are not at their blood pressure targets (9,10). In 1 of these studies, only 13% achieved the composite triple target (10). Furthermore, less than one-half of the patients with hyperlipidemia were reportedly receiving the appropriate treatment (9). Guidelines recommend using CVD risk assessment equations to guide prevention and management (11). Despite this, calculated risk assessment is often not integrated into clinicians’ daily routine. In 1 study, the majority of the patients attending physician clinics reported that they had never undergone cardiovascular risk assessment (11). Taken together, the high prevalence of CVD and suboptimal assessment and management of risk factors indicate the need to consider alternative approaches to this major public health problem.
Community pharmacists are accessible primary health care professionals who frequently see patients with chronic diseases (12); as such, they are well positioned to identify patients with or at high risk for CVD, assess such risk, and assist in their disease management. The efficacy of pharmacist intervention on individual CVD risk factors has been well demonstrated (13–17); however, their role in targeting multiple risk factors to reduce overall CVD risk has not been determined. Expansion of the scope of practice of pharmacists, such as in Alberta, Canada, provides an opportunity for pharmacists to independently prescribe and order laboratory tests. These added privileges might help address the phenomenon of therapeutic inertia (18) in the community.
With the RxEACH (Alberta Vascular Risk Reduction Community Pharmacy Project) study, we sought to develop and implement a broad-based, community, pharmacist-initiated vascular risk reduction case-finding and intervention program in patients at high risk for CVD and to evaluate its impact on risk for cardiovascular events.
The RxEACH study was a multicenter, randomized controlled trial (Figure 1), conducted in 56 community pharmacies in the province of Alberta, Canada.
We included adults (≥18 years of age) who were at high risk for cardiovascular events: those with diabetes; chronic kidney disease (CKD) (estimated glomerular filtration rate of <60 ml/min/1.73 m2 on 2 consecutive measurements within a 3-month period, or albumin-to-creatinine ratio ≥30 in a single measurement or between 3 and 29 on 2 consecutive measurements within a 3-month period); established atherosclerotic vascular disease (via patient health records or self-report) including cerebrovascular disease (prior stroke or transient ischemic attack), coronary artery disease (myocardial infarction, acute coronary syndrome, stable angina, or revascularization) or peripheral arterial disease (symptomatic and/or ankle brachial index <0.9), or primary prevention patients with multiple risk factors and Framingham risk score >20%. In addition, subjects must have had at least 1 uncontrolled risk factor: blood pressure >140/90 or >130/80 mm Hg if diabetic, low-density lipoprotein cholesterol (LDL-C) >2.0 mmol/l, HbA1c >7.0%, or current smoker.
We excluded patients who were unwilling to participate or provide written informed consent, were unwilling or unable to participate in regular follow-up visits, or were pregnant.
Pharmacists used a proactive case-finding strategy (19) to identify potential participants, which focused on their high-risk patients who were receiving metformin (as a marker for type 2 diabetes), clopidogrel or acetylsalicylic acid (for coronary artery disease), antihypertensive agents, statins for dyslipidemic patients, and known smokers. Additionally, pharmacists used newspaper or other advertising outlets, or pharmacy heart health clinics.
After obtaining written informed consent, patients were randomized in a 1:1 ratio to intervention or usual care groups using a centralized secure website at the data management center (Epidemiology Coordinating and Research [EPICORE] Centre). The randomization scheme was blocked (random block size) and stratified by pharmacy.
Baseline assessment of cardiovascular risk factors was conducted and the patient’s family physician was informed of the patient’s inclusion into the study. Any subsequent changes made to participant treatment regimens were also communicated to the physician (as per usual pharmacist practice in Alberta).
Patients randomized to the intervention group received a Medication Therapy Management consultation from their pharmacist (in Alberta, called a Comprehensive Annual Care Plan or Standard Medication Management Assessment), which included:
• Patient assessment: blood pressure measurement according to Canadian Hypertension Education Program guidelines (20), waist circumference, and weight and height measurements.
• Laboratory assessment: HbA1c, fasting cholesterol profile (if not done within the past 3 months), estimated glomerular filtration rate, and albumin-to-creatinine ratio (if not done within the past 12 months).
• Individualized assessment: CVD risk and education about this risk.
◦ Cardiovascular risk was calculated using an online tool. Our system used the appropriate risk engine on the basis of the patient’s medical history: the UKPDS (United Kingdom Prospective Diabetes Study) risk engine (21) for patients with diabetes, the International model for prediction of recurrent CVD (22) for those with previous vascular disease, and the Framingham risk score (23) for patients with CKD or primary prevention patients at high risk for cardiovascular events. In the case where a patient had >1 comorbidity, the risk engine estimating the highest risk was used.
◦ Discussion of CVD risk with the patient using an interactive online tool to explain his or her individual cardiovascular risk, targets for intervention, and healthy life-style options.
• Providing treatment recommendations based on the most up-to-date Canadian clinical practice guidelines for cardiovascular risk factors.
• Prescription adaptation(s), and/or de novo prescriptions where necessary to meet lipid, blood pressure, and glycemic control targets and smoking cessation.
• Regular communication with the patient’s family physician after each contact with the patient.
• Regular follow-up with all patients a minimum of every 3 to 4 weeks for 3 months.
Pharmacists in Alberta can bill the provincial health plan for providing such services.
Patients randomized to the usual care group received usual pharmacist and physician care with no specific interventions for 3 months. At the end of that period, all patients were offered the intervention as outlined previously.
The primary outcome was the difference in change in estimated cardiovascular risk between intervention and usual care groups at 3 months. We defined cardiovascular risk as the risk for future cardiovascular events (e.g., myocardial infarction, revascularization, cardiovascular death) as calculated by the validated risk engines as discussed previously. Secondary outcomes included the difference in change in individual cardiovascular risk factors between intervention and usual care groups at 3 months, including systolic and diastolic blood pressure, LDL-C, HbA1c, and smoking cessation.
Sample size and analytical plan
Using the information from Grover et al. (24) (baseline CVD risk and SD), a reduction in estimated risk for cardiovascular events of 25% in the intervention group and 17.5% in the control group (absolute difference: 7.5%), assuming 90% power and a 2-sided alpha of 0.05, required an overall sample size of 674 patients (337 in each group). This sample size was inflated to 704 (352 in each group) to account for possible dropouts, losses to follow-up, and withdrawals of consent.
All analyses were conducted on an intention-to-treat basis. In the case of missing data, a last observation carried forward approach was used. The primary outcome was analyzed using analysis of covariance, adjusting for center effect and all covariates with p < 0.25 between groups. Secondary outcomes of blood pressure, LDL-C, and HbA1c were analyzed using analysis of covariance, adjusting for center effect and all covariates with p < 0.25 between groups. Smoking cessation was analyzed using the chi-square test.
The EPICORE Centre provided the data and trial management and biostatistical support.
Pharmacist training was on the basis of current Canadian guidelines (25–30). The research team developed an online training program that was reviewed internally and externally for content validity. The training program was hosted online at the Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta server, and provided at face-to-face regional meetings. The training program included modules on case finding, cardiovascular risk calculation, and patient communication of cardiovascular risk, CKD, hypertension, dyslipidemia, diabetes, smoking cessation, diet and lifestyle management, and documentation of care plans for remuneration by Alberta Health. A hotline was made available for participating pharmacists to connect them with experts in cardiovascular risk reduction and study procedures.
The RxEACH study was approved by the Health Research Ethics Boards of the University of Alberta and the University of Calgary.
The RxEACH trial began enrollment on January 27, 2014, with 56 sites (pharmacies) involved (for list of pharmacist investigators, see the Online Appendix). A total of 913 subjects were screened, 827 of whom were eligible. We randomized 723 patients; 353 were assigned to usual care and 370 to intervention (Figure 1). The last patient was enrolled June 3, 2015, and follow-up was completed September 24, 2015. There were 10 early withdrawals in the usual care group (2.8%) and 19 in the intervention group (5.1%), mostly because of losses to follow-up in both groups.
The 2 treatment groups were well balanced in baseline demographic and clinical parameters (Table 1). The average age was 62 ± 12 years, and 58% were male. In terms of CVD risk factors, 84% had hypertension, 83% had dyslipidemia, 64% reported sedentary life-style, 27% were smokers, and mean body mass index was 34 ± 13.2 kg/m2. In addition, 79% had diabetes, 40% had CKD, and 30% had atherosclerotic vascular disease (stroke/transient ischemic attack, acute coronary syndromes, angina, revascularization, or peripheral arterial disease). A total of 53 were primary prevention patients at high risk for cardiovascular events (Framingham risk >20%). The inclusion criteria for the study required the presence of at least 1 poorly controlled risk factor; of these, 79% (of those with diabetes) had poor glycemic control as measured by HbA1c, 72% had poorly controlled blood pressure, 59% had poorly controlled dyslipidemia, and 27% were smokers (categories not mutually exclusive).
At the baseline visit, mean blood pressure was 137 ± 20/81 ± 12 mm Hg, total cholesterol was 4.3 ± 1.0 mmol/l, LDL-C was 2.4 ± 1.2 mmol/l, and high-density lipoprotein cholesterol was 1.2 ± 0.4 mmol/l. In the 573 patients with diabetes, the average duration of diabetes was 12 ± 11 years, and mean HbA1c was 8.6 ± 2%. Estimated baseline cardiovascular risk was 26.6 ± 19.3% in the usual care group and 25.6 ± 17.8% in the intervention group (Table 1).
Estimated cardiovascular risk changed over the 3-month follow-up period from 26.6 ± 19.3% to 25.9 ± 19.6% in the usual care group, compared with 25.6 ± 17.8% at baseline to 20.5 ± 15.9% in the intervention group. This, when adjusted for baseline characteristics and the center effect, corresponded to a relative decrease in estimated cardiovascular risk of 21% (an absolute difference of 5.37; 95% confidence interval: 4.17 to 6.56; p < 0.001) (Figure 2), the primary outcome.
Table 2 outlines medication use and changes that were made in the study population and shows more changes in hypoglycemic, hypertension, and dyslipidemia medications in the intervention group. In regard to secondary outcomes, significant reductions were seen in the intervention group in LDL-C, blood pressure, HbA1c, and smoking (Table 3). Figure 3 shows achievement of targets for LDL-C, blood pressure, HbA1c, and smoking, with the intervention group showing improvements across all categories. Body mass index changed from 34.08 ± 15.3 kg/m2 to 32.9 ± 8.0 kg/m2 in the usual care group and from 33.27 ± 10.8 kg/m2 to 32.6 ± 8.8 kg/m2 in the intervention group. There were no adverse events reported during the trial.
CVD remains the most important cause of death and disability worldwide (1). Although the risk factors for CVD are well known, poor identification of those at risk and poor control of these factors remain an enigma (5–10). In the RxEACH study, we found that engaging community pharmacists in identifying at-risk candidates (case finding) and managing their cardiovascular risk factors using an advanced scope of practice that included prescribing and ordering laboratory tests resulted in a 21% reduction in their risk for cardiovascular events in only 3 months (Central Illustration). Because pharmacists are highly accessible primary health care providers, this could have major public health implications in reducing the burden of CVD if these practices were widely adopted.
Our results add to an already rich literature on the efficacy of pharmacist care on the individual components of cardiovascular risk factors. These nonprescribing trials have been elegantly summarized in a meta-analysis by Santschi et al. (15), who noted significant improvements in dyslipidemia, hypertension, and smoking cessation. Furthermore, our group recently published trials of independent pharmacist prescribing in patients with poorly controlled diabetes (31) and hypertension (32). To our knowledge, the RxEACH study was the first large-scale randomized trial of overall cardiovascular risk reduction, targeting multiple risk factors together.
O’Donovan et al. (33) conducted a literature review to study pharmacist use of cardiovascular screening tools and reported that the majority of the screenings were either opportunistic or referral-based. They highlighted the lack of a proactive case-finding approach in such programs. Our results took their findings to the next level. They were consistent with the findings of McNamara et al. (34,35) who conducted a pilot longitudinal pre- and post-test study to evaluate the impact of a medication review and educational intervention on patient cardiovascular risk in a community pharmacy setting and reported a significant cardiovascular risk reduction over a 6-month period. The RxEACH trial also validated the merits of a broader scope of practice for pharmacists; in this case, of independent prescribing authority and ability to order and interpret laboratory tests.
Indeed, we reported recently that of the patients receiving baseline assessments in the RxEACH trial, 290 had CKD, of whom 40% had previously unrecognized CKD (i.e., was only identified by the pharmacist in the course of targeted screening for CKD) (36,37). As a practice-based trial of an approach to cardiovascular risk reduction, we can only speculate that the improvements seen were due to changes in medication use (as seen in Table 2), dosage adjustment, and improved adherence to lifestyle and medications—all of which were enhanced by the guidelines-recommended follow-up visits performed by the pharmacists.
A number of strengths and limitations warrant mention. Use of a randomized controlled design portends a high level of causal inference. In terms of sustainability of the intervention, we used the medication management remuneration program already established by the Alberta government (and also present to various extents in most U.S. states) that reimburses pharmacists for their care. Indeed, our study could be seen as a validation of these medication management programs.
With respect to limitations, our follow-up duration was relatively short. The reason for this short duration was a compromise decision made because investigators (pharmacists) had expressed concerns over “usual care” in these high-risk patients. We decided to shorten the follow-up duration to 3 months and allow patients allocated to usual care to cross over to receive the intervention after 3 months. While 3-month outcomes for smoking cessation are rather short (and could certainly be subject to recidivism), they may bias against the intervention because of the short duration to achieve reductions in LDL-C (which responds slowly to medication changes), blood pressure (which often takes several weeks to see the full effects of a medication change), and HbA1c (which takes up to 3 months to show full effects of changes in glycemic control). As such, we may be underestimating the impact on these parameters. Another potential limitation is generalizability to other pharmacists in other jurisdictions, as pharmacists in the province of Alberta certainly have a broad scope of practice that includes independent prescribing and the ability to order laboratory tests. However, while there is variability across jurisdictions in North America regarding scope of practice, many also allow pharmacists to conduct medication management reviews, adjust and adapt prescriptions, make recommendations to physicians, and receive remuneration for these activities. Training on cardiovascular risk reduction is widely available and should not limit generalizability of our findings. We used risk estimation equations for our primary outcome. We acknowledge that these equations were not designed to measure change. Nevertheless, we wished to capture the overall effect of a cardiovascular risk reduction program and reported a relative reduction in risk (as such, biases and limitations would presumably be equally present at baseline and at the end of follow-up for all patients). Similarly, the lack of a validated equation for patients with CKD almost certainly underestimated the risk for these patients; but again, reporting of a relative reduction in risk should alleviate this concern. With regard to smoking cessation, we used patient self-report and assessment by the pharmacist to determine smoking status rather than methods such as carbon monoxide detection. Finally, due to the nature of the intervention, we could not blind investigators to treatment allocation.
CVDs remain important public health problems in the United States, Canada, and worldwide (1). As such, our study demonstrating the impact of an advanced scope of pharmacist practice might have important public health implications. Indeed, engaging pharmacists could bring to bear another 450,000 helping hands in the United States and Canada to help reduce the burden of CVD. It is important to note that the reductions in cardiovascular risk were achieved on top of (not instead of) usual physician care. Interprofessional communication and collaboration remain key. We would encourage policymakers to consider broadening the scope of practice of pharmacists (as in Alberta) and for pharmacists and professional pharmacy organizations to seize these opportunities for the betterment of patient care.
CVDs and their associated risk factors remain an important public health problem. In the RxEACH study, we demonstrated that pharmacists with an advanced scope of practice could identify patients with poorly controlled risk factors and significantly reduce their risk for cardiovascular events. Adopting these practice innovations could have major public health benefits.
COMPETENCY IN SYSTEMS-BASED PRACTICE: Advanced practice pharmacists, in partnership with physicians, can identify and manage risk factors and promote a significant reduction in cardiovascular events in the communities they serve.
TRANSLATIONAL OUTLOOK: Further efforts by health policy makers are needed to expand the scope of practice of appropriately trained pharmacists, develop innovative reimbursement systems, and optimize the impact of team-based cardiovascular care.
Funding for the RxEACH study was provided by Alberta Health, and the Cardiovascular Health and Stroke Strategic Clinical Network of Alberta Health Services. Merck Canada provided the funds to develop the educational materials. None of these sponsors had any role in the design, conduct, collection, analysis or interpretation or data or the preparation, review or approval of this manuscript. Dr. Tsuyuki has received investigator-initiated research grants from Merck, Sanofi, and AstraZeneca; and has served as a consultant for Merck. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- chronic kidney disease
- cardiovascular disease
- glycosylated hemoglobin
- low-density lipoprotein cholesterol
- Received February 29, 2016.
- Revision received March 24, 2016.
- Accepted March 25, 2016.
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