RESEARCH NOTES
Pharmacists on primary care teams: Effect on antihypertensive medication management in patients with type 2 diabetes Dima Omran, Sumit R. Majumdar, Jeffrey A. Johnson, Ross T. Tsuyuki, Richard Z. Lewanczuk, Lisa M. Guirguis, Mark Makowsky, and Scot H. Simpson
M
ore than 9.5% of the global population has diabetes, with the majority (90% or more) having type 2 diabetes.1 Adults with diabetes have
Dima Omran, BSc(Pharm), MSc, Graduate Student, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada Sumit R. Majumdar, MD, MPH, Professor, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada Jeffrey A. Johnson, BSP, PhD, Professor, School of Public Health, University of Alberta, Edmonton, Alberta, Canada Ross T. Tsuyuki, BSc(Pharm), PharmD, MSc, Professor, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Abstract Objective: To identify which activities produced a significant improvement in blood pressure control in patients with type 2 diabetes when pharmacists were added to primary care teams. Methods: This prespecified, secondary analysis evaluated medication management data from a randomized controlled trial. The primary outcome was a change in treatment, defined as addition, dosage increase, or switching of an antihypertensive medication during the 1-year study period. The secondary outcome was a change in antihypertensive medication adherence using the medication possession ratio (MPR). Results: The 200 evaluable trial patients had a mean age of 59 (SD, 11) years, 44% were men, and mean blood pressure was 130 (SD, 16)/74 (SD, 10) mm Hg at baseline. Treatment changes occurred in 45 (42%) of 107 patients in the intervention group and 24 (26%) of 93 patients in the control group (RR, 1.63; 95% CI, 1.08–2.46). Addition of a new medication was the most common type of change, occurring in 34 (32%) patients in the intervention group and 17 (18%) patients in the control group (P = 0.029). Adherence to antihypertensive medication was high at baseline (MPR, 93%). Although medication adherence improved in the intervention group (MPR, 97%) and declined in the control group (MPR, 91%), the difference between groups was not significant (P = 0.21). Conclusion: The observed improvement in blood pressure control when pharmacists were added to primary care teams was likely achieved through antihypertensive treatment changes and not through improvements in antihypertensive medication adherence. J Am Pharm Assoc. 2015;55:265–268. doi: 10.1331/JAPhA.2015.14225 Journal of the American Pharmacists Association
Richard Z. Lewanczuk, MD, PhD, Professor, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada Lisa M. Guirguis, BSc(Pharm), PhD, Associate Professor, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada Mark Makowsky, BSP, PharmD, Associate Professor, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada Scot H. Simpson, BSP, PharmD, MSc, Professor, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada Correspondence: Scot H. Simpson, BSP, PharmD, MSc, Faculty of Pharmacy and Pharmaceutical Sciences, 3–171 Edmonton Clinic Health Academy, University of Alberta, 11405 87 Ave., Edmonton, AB T6G 1C9, Canada; scot@ ualberta.ca Funding: Mrs. Omran was supported by scholarships through the Alberta Diabetes Institute (ADI) and the Alliance for Canadian Health Outcomes Research in Diabetes (ACHORD) Training Program. Dr. Simpson was supported as a New Investigator by the Canadian Institutes of Health Research (CIHR). Dr. Majumdar is supported as a Health Scholar by the Alberta Innovates – Health Solutions (AIHS) and holds the Endowed Chair in Patient Health Management of the Faculties of Medicine and Dentistry and Pharmacy and Pharmaceutical Sciences, University of Alberta. Dr. Johnson holds a Health Senior Scholar through the AIHS, and is Chair of the CIHR funded Alliance for Canadian Health Outcomes Research in Diabetes (ACHORD) (reference no. OTG88588).Operating grant funding provided by the Canadian Diabetes Association, Institute of Health Economics, and Alberta Heritage Foundation for Medical Research (AHFMR). Disclosure: The authors declare no relevant conflicts of interest or financial relationships. Acknowledgments: To the two pharmacists in this study, Denise Nitschke, BSc(Pharm), CDE, and Shelley Tuchsherer, BSc(Pharm), CDE.; staff at the Epidemiology Coordinating and Research Centre for support; and clinicians and staff of the five family medicine clinics in the Edmonton Southside Primary Care Network for support. Previous presentation: 16th Annual Canadian Diabetes Association/Canadian Society of Endocrinology and Metabolism (CDA/CSEM) Professional Conference & Annual Meetings, Montreal, Quebec, Canada, October 19, 2013. Received October 7, 2014. Accepted for publication November 11, 2014. Published online in advance of print April 24, 2015.
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a 2-fold higher risk of developing cardiovascular diseases and a significantly higher mortality rate compared with the general population.2,3 Among the modifiable cardiovascular risk factors, hypertension is the most common comorbidity in patients with type 2 diabetes.4 If blood pressure is not optimally controlled, it significantly increases the risk of cardiovascular disease and diabetes-related death.5 Recognizing the importance of blood pressure control in diabetes management, clinical practice guidelines recommend a long-term, comprehensive program that encompasses healthy lifestyle choices and optimal medication management.6 Success of these programs depends on a strong collaborative team of health professionals, including pharmacists.7 Although the proportion of patients with diabetes achieving blood pressure targets has improved from 12% to 36%, there is still room for improvement.4,8 Possible barriers to additional improvements include clinical inertia, defined as the reluctance to initiate or intensify treatment despite suboptimal blood pressure, and poor adherence to prescribed medication.9,10 To address the concerns of clinical inertia and poor medication adherence, we tested the hypothesis that adding pharmacists to primary care teams could improve blood pressure management in patients with type 2 diabetes.11 In previously published articles, our study found that the addition of a pharmacist resulted in significant and clinically important reductions in blood pressure and also reductions in the predicted 10-year risk of cardiovascular disease.11,12 Other groups have also reported significant improvements in cardiovascular risk factors when pharmacists were involved in diabetes management.13,14 However, the exact pharmacist activities responsible for the observed improvements remain unclear.
Objectives Using data obtained from a randomized controlled trial,11 this analysis sought to determine whether observed improvements in blood pressure resulted from pharmacists’ recommendations to improve antihypertensive medication management or patients’ adherence to antihypertensive medications.
Methods Details of the methods used in the randomized controlled trial were registered before patient recruitment (ISRCTN97121854); results of the main trial and changes to the predicted 10-year risk of cardiovascular diseases have been reported previously.11,12 This prespecified substudy is a secondary analysis of data collected during the main study. Inclusion criteria All 260 patients enrolled in the main study were eligible 266 JAPhA | 5 5:3 | M AY /JUN 2 0 1 5
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for inclusion in both analyses of this substudy.11 Patients were included in the treatment change analysis if their pharmacy dispensing records were available. Patients were included in the adherence analysis if they had sufficient information to calculate a medication possession ratio (MPR).15 Antihypertensive treatment change analysis Our first objective was to examine the effect of pharmacist intervention on changes to antihypertensive medication management. Patients’ dispensing records during the 6-month period before enrollment in the main study were reviewed to establish a baseline antihypertensive medication regimen. Any changes to the baseline regimen during the final 6 months of the main study followup were identified and categorized as addition, dosage increase, or switching of antihypertensive medications. The primary outcome for this objective was a composite binary outcome of any of these treatment changes. Individuals with more than one treatment change were counted only once for the primary outcome analysis. We also evaluated each component of the primary composite outcome separately. We compared the proportions of patients in each group with at least one treatment change using the chisquare test. We also calculated the relative risk (RR) and 95% confidence interval (95% CI) to measure the association between treatment groups and treatment changes and to measure the association between treatment changes and achievement of clinically important reductions in blood pressure (defined as a 10% or more reduction in systolic blood pressure during the 1-year study period).11 Similar analyses were conducted for each component of the primary outcome. Medication adherence analysis Our second objective was to evaluate the effect of pharmacist intervention on adherence to antihypertensive medications. Medication adherence was measured using the MPR, which was calculated using a standard formula.15 The mean MPR for all antihypertensive medications was then calculated for the 6-month period before enrollment in the main study and for the final 6 months of the main study follow-up period. We used a paired t test to examine the changes in MPR from baseline to follow-up for intervention and control groups. A Student’s t test was used to test for between-group differences in the MRP change.
Results Pharmacy dispensing records were not available for 60 (23%) of the 260 patients enrolled in the main study.11 There were no significant differences in baseline characteristics between these 60 patients and the 200 patients included in this substudy. Mean age of the 200 patients with dispensing records was 59.4 (SD, 11.2) years, 44% Journal of the American Pharmacists Association
RESEARCH NOTES
were men, and mean blood pressure was 130 (SD, 16)/74 (SD, 10) mm Hg at baseline (Table 1). Antihypertensive treatment change analysis During the study period, there were 116 antihypertensive treatment changes. At least one change occurred in 45 (42%) of the 107 patients in the intervention group and 24 (26%) of the 93 patients in the control group (RR = 1.63; 95% CI, 1.08–2.46; P = 0.016) (Table 2). Addition of a new antihypertensive medication accounted for 68 (58%) of the treatment changes and occurred more often in the intervention group than in the control group (RR = 1.74; 95% CI, 1.04–2.90; P = 0.029). Angiotensin converting enzyme inhibitors were the most common antihypertensive medications added, followed by angiotensin II receptor blockers and hydrochlorothiazide. There were 35 dosage increases in 28 patients and 13 antihypertensive medication switches in 10 patients. Although the between-group differences were not significant (P > 0.05, for both comparisons), there were clinically important changes in the intervention group. For instance, one patient had difficulty achieving recommended blood pressure targets because of reflex tachycardia. The pharmacist recommended switching amlodipine to diltiazem and the patient was able to achieve better blood pressure control without adverse reactions. Patients in the intervention group with antihypertensive treatment changes were more likely to have an improvement in blood pressure control compared with patients in the intervention group with no treatment changes (RR = 2.07; 95% CI, 1.25–3.42; P = 0.004). In contrast, there was no significant association between treatment change and blood pressure among patients in the control group (RR = 0.96; 95% CI, 0.47–1.97; P = 0.91). Medication adherence analysis Of the 200 patients with pharmacy dispensing records, 43 patients were never dispensed antihypertensive medication and 6 patients had only one fill for antihypertensive medication. Adherence to antihypertensive medication was high (MPR ± SD, 93.4% ± 29.1%) and similar between groups at baseline (P = 0.70). The mean MPR change was a 3.5% absolute increase in the intervention group and a 4.1% absolute decrease in the control group; however, the difference between groups was not significant (P = 0.21).
Discussion We used data from 200 patients enrolled in a randomized controlled trial to identify which pharmacist activities were responsible for observed improvements in blood pressure.11 Patients in the intervention group were more likely to have antihypertensive treatment changes, which also led to clinically important reductions in blood pressure. There were fewer treatment changes in the control group. Moreover, these changes Journal of the American Pharmacists Association
Table 1. Baseline demographic and clinical characteristics of patients in study Characteristics Age, years (SD) Men, n (%) Diabetes duration, years (SD) Systolic blood pressure, mm Hg (SD) Diastolic blood pressure, mm Hg (SD) Blood pressure ≥130/80 mm Hg, n (%) Current smoker, n (%) Vascular disease, n (%) Blood pressure medications, n (%): None 1 2 3 or more
Intervention Control group P group (n = 107) (n = 93) value 59 (11) 46 (43)
60 (12) 41 (44)
0.40 0.88
5 (4)
7 (8)
0.029
131 (15)
128 (16)
0.20
75 (10)
72 (11)
0.16
70 (65) 7 (7) 23 (22)
49 (53%) 9 (10) 20 (22)
0.067 0.41 0.99
29 (27) 34 (32) 18 (17) 26 (25)
31 (33) 24 (26) 21 (23) 17 (18)
0.46
Table 2. Antihypertensive medication changes in patients in intervention and control groups Activity
Any antihypertensive treatment optimization Addition of new antihypertensive medication Dosage increase in antihypertensive medication Switching antihypertensive medications
No. patients (% of total) Intervention Control group P group (n = 107) (n = 93) valuea 45 (42)
24 (26)
0.016
34 (32)
17 (18)
0.029
18 (17)
10 (11)
0.22
6 (6)
4 (4)
0.67
Chi-square test
a
did not appear to be associated with changes in blood pressure among the control group. Observations from this substudy are consistent with those reported by Heisler and colleagues, who examined the effect of a clinical pharmacist outreach program for patients with type 2 diabetes and hypertension.16 Although Heisler et al. reported a higher proportion of patients in their intervention group with medication changes (70%) compared with our study (42%), two differences between these studies are important. First, Heisler et al. included patients with persistently poor blood pressure control and poor adherence; patients in our study had high adherence rates at baseline. Second, pharmacists in the study by Heisler et al. were authoj apha.org
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rized to make changes to antihypertensive medications; pharmacists in our study did not have prescribing authorization. Regardless of the differences, both studies provide randomized controlled trial evidence supporting addition of pharmacists to primary care teams. In contrast to the benefit of pharmacist activities on treatment changes, we did not observe any significant effects on medication adherence. These observations are not consistent with previous reports of pharmacist intervention on adherence to antihypertensive therapies.17 However, the median baseline adherence rate of studies included in the review by Morgado and colleagues was 68%. Our study group had a high baseline adherence rate (93%), which limited our ability to detect differences between groups.
Limitations Several limitations should be considered when interpreting the results of our study. Volunteer bias may have influenced the observations, especially because baseline adherence rates were higher than previous reports.17 Pharmacists in the study provided recommendations to the prescribing physician rather than making drug therapy changes directly. Observations from previous studies suggest that the effect of pharmacist intervention is higher if they have prescribing authorization.13,16 We used pharmacy dispensing records to identify changes to antihypertensive medication management. Communications between study pharmacists and prescribing physicians were not recorded; the true impact of the intervention may be underestimated.
Conclusion The significant and clinically important reduction in blood pressure observed in a randomized controlled trial was likely due to pharmacists’ changes in antihypertensive medication management rather than antihypertensive medication adherence. These observations support the addition of pharmacists to primary care teams that help patients with type 2 diabetes.
References 1. Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet. 2011;378:31–40. 2. Sarwar N, Gao P, Kondapally Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–2222. 3. Gregg EW, Cheng YJ, Saydah S, et al. Trends in death rates among U.S. adults with and without diabetes between 1997 and 2006: findings from the National Health Interview Survey. Diabetes Care. 2012;35:1252–1257.
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4. Leiter LA, Berard L, Bowering CK, et al. Type 2 diabetes mellitus management in Canada: is it improving? Can J Diabetes. 2013;37:82–89. 5. Stratton IM, Cull CA, Adler AI, et al. Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia. 2006;49:1761–1769. 6. Stone JA, Fitchett DH, Grover S, et al. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada: vascular protection in people with diabetes. Can J Diabetes. 2013;37:S100–S104. 7. Davidson MB. Detailed treatment algorithms for effective nurseand pharmacist-directed diabetes care: a personal approach. Diabetes Educ. 2009;35:61–71. 8. McLean DL, Simpson SH, McAlister FA, et al. Treatment and blood pressure control in 47,964 people with diabetes and hypertension: a systematic review of observational studies. Can J Cardiol. 2006;22:855–860. 9. Phillips LS, Branch WT, Cook CB, et al. Clinical inertia. Ann Intern Med. 2001;135:825–834. 10. Schmittdiel JA, Uratsu CS, Karter AJ, et al. Why don’t diabetes patients achieve recommended risk factor targets? Poor adherence versus lack of treatment intensification. J Gen Intern Med. 2008;23:588–594. 11. Simpson SH, Majumdar SR, Tsuyuki RT, et al. Effect of adding pharmacists to primary care teams on blood pressure control in patients with type 2 diabetes: a randomized controlled trial. Diabetes Care. 2011;34:20–26. 12. Ladhani NN, Majumdar SR, Johnson JA, et al. Adding pharmacists to primary care teams reduces predicted long-term risk of cardiovascular events in type 2 diabetic patients without established cardiovascular disease: results from a randomized trial. Diabet Med 2012;29:1433–1439. 13. 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;118:276–284. 14. McLean DL, McAlister FA, Johnson JA, et al. 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;168:2355–2361. 15. Raebel MA, Schmittdiel J, Karter AJ, et al. Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases. Med Care. 2013;51:S11–S21. 16. Heisler M, Hofer TP, Schmittdiel JA, et al. Improving blood pressure control through a clinical pharmacist outreach program in patients with diabetes mellitus in 2 high-performing health systems: the adherence and intensification of medications cluster randomized, controlled pragmatic trial. Circulation. 2012;125:2863–2872. 17. Morgado MP, Morgado SR, Mendes LC, et al. Pharmacist interventions to enhance blood pressure control and adherence to antihypertensive therapy: review and meta-analysis. Am J Health Syst Pharm. 2011;68:241–253.
Journal of the American Pharmacists Association
Pharmacists on primary care teams: Effect on antihypertensive medication management in patients with type 2 diabetes Dima Omran, Sumit R. Majumdar, Jeffrey A. Johnson, Ross T. Tsuyuki, Richard Z. Lewanczuk, Lisa M. Guirguis, Mark Makowsky, and Scot H. Simpson
M
ore than 9.5% of the global population has diabetes, with the majority (90% or more) having type 2 diabetes.1 Adults with diabetes have
Dima Omran, BSc(Pharm), MSc, Graduate Student, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada Sumit R. Majumdar, MD, MPH, Professor, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada Jeffrey A. Johnson, BSP, PhD, Professor, School of Public Health, University of Alberta, Edmonton, Alberta, Canada Ross T. Tsuyuki, BSc(Pharm), PharmD, MSc, Professor, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Abstract Objective: To identify which activities produced a significant improvement in blood pressure control in patients with type 2 diabetes when pharmacists were added to primary care teams. Methods: This prespecified, secondary analysis evaluated medication management data from a randomized controlled trial. The primary outcome was a change in treatment, defined as addition, dosage increase, or switching of an antihypertensive medication during the 1-year study period. The secondary outcome was a change in antihypertensive medication adherence using the medication possession ratio (MPR). Results: The 200 evaluable trial patients had a mean age of 59 (SD, 11) years, 44% were men, and mean blood pressure was 130 (SD, 16)/74 (SD, 10) mm Hg at baseline. Treatment changes occurred in 45 (42%) of 107 patients in the intervention group and 24 (26%) of 93 patients in the control group (RR, 1.63; 95% CI, 1.08–2.46). Addition of a new medication was the most common type of change, occurring in 34 (32%) patients in the intervention group and 17 (18%) patients in the control group (P = 0.029). Adherence to antihypertensive medication was high at baseline (MPR, 93%). Although medication adherence improved in the intervention group (MPR, 97%) and declined in the control group (MPR, 91%), the difference between groups was not significant (P = 0.21). Conclusion: The observed improvement in blood pressure control when pharmacists were added to primary care teams was likely achieved through antihypertensive treatment changes and not through improvements in antihypertensive medication adherence. J Am Pharm Assoc. 2015;55:265–268. doi: 10.1331/JAPhA.2015.14225 Journal of the American Pharmacists Association
Richard Z. Lewanczuk, MD, PhD, Professor, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada Lisa M. Guirguis, BSc(Pharm), PhD, Associate Professor, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada Mark Makowsky, BSP, PharmD, Associate Professor, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada Scot H. Simpson, BSP, PharmD, MSc, Professor, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada Correspondence: Scot H. Simpson, BSP, PharmD, MSc, Faculty of Pharmacy and Pharmaceutical Sciences, 3–171 Edmonton Clinic Health Academy, University of Alberta, 11405 87 Ave., Edmonton, AB T6G 1C9, Canada; scot@ ualberta.ca Funding: Mrs. Omran was supported by scholarships through the Alberta Diabetes Institute (ADI) and the Alliance for Canadian Health Outcomes Research in Diabetes (ACHORD) Training Program. Dr. Simpson was supported as a New Investigator by the Canadian Institutes of Health Research (CIHR). Dr. Majumdar is supported as a Health Scholar by the Alberta Innovates – Health Solutions (AIHS) and holds the Endowed Chair in Patient Health Management of the Faculties of Medicine and Dentistry and Pharmacy and Pharmaceutical Sciences, University of Alberta. Dr. Johnson holds a Health Senior Scholar through the AIHS, and is Chair of the CIHR funded Alliance for Canadian Health Outcomes Research in Diabetes (ACHORD) (reference no. OTG88588).Operating grant funding provided by the Canadian Diabetes Association, Institute of Health Economics, and Alberta Heritage Foundation for Medical Research (AHFMR). Disclosure: The authors declare no relevant conflicts of interest or financial relationships. Acknowledgments: To the two pharmacists in this study, Denise Nitschke, BSc(Pharm), CDE, and Shelley Tuchsherer, BSc(Pharm), CDE.; staff at the Epidemiology Coordinating and Research Centre for support; and clinicians and staff of the five family medicine clinics in the Edmonton Southside Primary Care Network for support. Previous presentation: 16th Annual Canadian Diabetes Association/Canadian Society of Endocrinology and Metabolism (CDA/CSEM) Professional Conference & Annual Meetings, Montreal, Quebec, Canada, October 19, 2013. Received October 7, 2014. Accepted for publication November 11, 2014. Published online in advance of print April 24, 2015.
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a 2-fold higher risk of developing cardiovascular diseases and a significantly higher mortality rate compared with the general population.2,3 Among the modifiable cardiovascular risk factors, hypertension is the most common comorbidity in patients with type 2 diabetes.4 If blood pressure is not optimally controlled, it significantly increases the risk of cardiovascular disease and diabetes-related death.5 Recognizing the importance of blood pressure control in diabetes management, clinical practice guidelines recommend a long-term, comprehensive program that encompasses healthy lifestyle choices and optimal medication management.6 Success of these programs depends on a strong collaborative team of health professionals, including pharmacists.7 Although the proportion of patients with diabetes achieving blood pressure targets has improved from 12% to 36%, there is still room for improvement.4,8 Possible barriers to additional improvements include clinical inertia, defined as the reluctance to initiate or intensify treatment despite suboptimal blood pressure, and poor adherence to prescribed medication.9,10 To address the concerns of clinical inertia and poor medication adherence, we tested the hypothesis that adding pharmacists to primary care teams could improve blood pressure management in patients with type 2 diabetes.11 In previously published articles, our study found that the addition of a pharmacist resulted in significant and clinically important reductions in blood pressure and also reductions in the predicted 10-year risk of cardiovascular disease.11,12 Other groups have also reported significant improvements in cardiovascular risk factors when pharmacists were involved in diabetes management.13,14 However, the exact pharmacist activities responsible for the observed improvements remain unclear.
Objectives Using data obtained from a randomized controlled trial,11 this analysis sought to determine whether observed improvements in blood pressure resulted from pharmacists’ recommendations to improve antihypertensive medication management or patients’ adherence to antihypertensive medications.
Methods Details of the methods used in the randomized controlled trial were registered before patient recruitment (ISRCTN97121854); results of the main trial and changes to the predicted 10-year risk of cardiovascular diseases have been reported previously.11,12 This prespecified substudy is a secondary analysis of data collected during the main study. Inclusion criteria All 260 patients enrolled in the main study were eligible 266 JAPhA | 5 5:3 | M AY /JUN 2 0 1 5
ja p h a.org
for inclusion in both analyses of this substudy.11 Patients were included in the treatment change analysis if their pharmacy dispensing records were available. Patients were included in the adherence analysis if they had sufficient information to calculate a medication possession ratio (MPR).15 Antihypertensive treatment change analysis Our first objective was to examine the effect of pharmacist intervention on changes to antihypertensive medication management. Patients’ dispensing records during the 6-month period before enrollment in the main study were reviewed to establish a baseline antihypertensive medication regimen. Any changes to the baseline regimen during the final 6 months of the main study followup were identified and categorized as addition, dosage increase, or switching of antihypertensive medications. The primary outcome for this objective was a composite binary outcome of any of these treatment changes. Individuals with more than one treatment change were counted only once for the primary outcome analysis. We also evaluated each component of the primary composite outcome separately. We compared the proportions of patients in each group with at least one treatment change using the chisquare test. We also calculated the relative risk (RR) and 95% confidence interval (95% CI) to measure the association between treatment groups and treatment changes and to measure the association between treatment changes and achievement of clinically important reductions in blood pressure (defined as a 10% or more reduction in systolic blood pressure during the 1-year study period).11 Similar analyses were conducted for each component of the primary outcome. Medication adherence analysis Our second objective was to evaluate the effect of pharmacist intervention on adherence to antihypertensive medications. Medication adherence was measured using the MPR, which was calculated using a standard formula.15 The mean MPR for all antihypertensive medications was then calculated for the 6-month period before enrollment in the main study and for the final 6 months of the main study follow-up period. We used a paired t test to examine the changes in MPR from baseline to follow-up for intervention and control groups. A Student’s t test was used to test for between-group differences in the MRP change.
Results Pharmacy dispensing records were not available for 60 (23%) of the 260 patients enrolled in the main study.11 There were no significant differences in baseline characteristics between these 60 patients and the 200 patients included in this substudy. Mean age of the 200 patients with dispensing records was 59.4 (SD, 11.2) years, 44% Journal of the American Pharmacists Association
RESEARCH NOTES
were men, and mean blood pressure was 130 (SD, 16)/74 (SD, 10) mm Hg at baseline (Table 1). Antihypertensive treatment change analysis During the study period, there were 116 antihypertensive treatment changes. At least one change occurred in 45 (42%) of the 107 patients in the intervention group and 24 (26%) of the 93 patients in the control group (RR = 1.63; 95% CI, 1.08–2.46; P = 0.016) (Table 2). Addition of a new antihypertensive medication accounted for 68 (58%) of the treatment changes and occurred more often in the intervention group than in the control group (RR = 1.74; 95% CI, 1.04–2.90; P = 0.029). Angiotensin converting enzyme inhibitors were the most common antihypertensive medications added, followed by angiotensin II receptor blockers and hydrochlorothiazide. There were 35 dosage increases in 28 patients and 13 antihypertensive medication switches in 10 patients. Although the between-group differences were not significant (P > 0.05, for both comparisons), there were clinically important changes in the intervention group. For instance, one patient had difficulty achieving recommended blood pressure targets because of reflex tachycardia. The pharmacist recommended switching amlodipine to diltiazem and the patient was able to achieve better blood pressure control without adverse reactions. Patients in the intervention group with antihypertensive treatment changes were more likely to have an improvement in blood pressure control compared with patients in the intervention group with no treatment changes (RR = 2.07; 95% CI, 1.25–3.42; P = 0.004). In contrast, there was no significant association between treatment change and blood pressure among patients in the control group (RR = 0.96; 95% CI, 0.47–1.97; P = 0.91). Medication adherence analysis Of the 200 patients with pharmacy dispensing records, 43 patients were never dispensed antihypertensive medication and 6 patients had only one fill for antihypertensive medication. Adherence to antihypertensive medication was high (MPR ± SD, 93.4% ± 29.1%) and similar between groups at baseline (P = 0.70). The mean MPR change was a 3.5% absolute increase in the intervention group and a 4.1% absolute decrease in the control group; however, the difference between groups was not significant (P = 0.21).
Discussion We used data from 200 patients enrolled in a randomized controlled trial to identify which pharmacist activities were responsible for observed improvements in blood pressure.11 Patients in the intervention group were more likely to have antihypertensive treatment changes, which also led to clinically important reductions in blood pressure. There were fewer treatment changes in the control group. Moreover, these changes Journal of the American Pharmacists Association
Table 1. Baseline demographic and clinical characteristics of patients in study Characteristics Age, years (SD) Men, n (%) Diabetes duration, years (SD) Systolic blood pressure, mm Hg (SD) Diastolic blood pressure, mm Hg (SD) Blood pressure ≥130/80 mm Hg, n (%) Current smoker, n (%) Vascular disease, n (%) Blood pressure medications, n (%): None 1 2 3 or more
Intervention Control group P group (n = 107) (n = 93) value 59 (11) 46 (43)
60 (12) 41 (44)
0.40 0.88
5 (4)
7 (8)
0.029
131 (15)
128 (16)
0.20
75 (10)
72 (11)
0.16
70 (65) 7 (7) 23 (22)
49 (53%) 9 (10) 20 (22)
0.067 0.41 0.99
29 (27) 34 (32) 18 (17) 26 (25)
31 (33) 24 (26) 21 (23) 17 (18)
0.46
Table 2. Antihypertensive medication changes in patients in intervention and control groups Activity
Any antihypertensive treatment optimization Addition of new antihypertensive medication Dosage increase in antihypertensive medication Switching antihypertensive medications
No. patients (% of total) Intervention Control group P group (n = 107) (n = 93) valuea 45 (42)
24 (26)
0.016
34 (32)
17 (18)
0.029
18 (17)
10 (11)
0.22
6 (6)
4 (4)
0.67
Chi-square test
a
did not appear to be associated with changes in blood pressure among the control group. Observations from this substudy are consistent with those reported by Heisler and colleagues, who examined the effect of a clinical pharmacist outreach program for patients with type 2 diabetes and hypertension.16 Although Heisler et al. reported a higher proportion of patients in their intervention group with medication changes (70%) compared with our study (42%), two differences between these studies are important. First, Heisler et al. included patients with persistently poor blood pressure control and poor adherence; patients in our study had high adherence rates at baseline. Second, pharmacists in the study by Heisler et al. were authoj apha.org
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RESEARCH NOTES
rized to make changes to antihypertensive medications; pharmacists in our study did not have prescribing authorization. Regardless of the differences, both studies provide randomized controlled trial evidence supporting addition of pharmacists to primary care teams. In contrast to the benefit of pharmacist activities on treatment changes, we did not observe any significant effects on medication adherence. These observations are not consistent with previous reports of pharmacist intervention on adherence to antihypertensive therapies.17 However, the median baseline adherence rate of studies included in the review by Morgado and colleagues was 68%. Our study group had a high baseline adherence rate (93%), which limited our ability to detect differences between groups.
Limitations Several limitations should be considered when interpreting the results of our study. Volunteer bias may have influenced the observations, especially because baseline adherence rates were higher than previous reports.17 Pharmacists in the study provided recommendations to the prescribing physician rather than making drug therapy changes directly. Observations from previous studies suggest that the effect of pharmacist intervention is higher if they have prescribing authorization.13,16 We used pharmacy dispensing records to identify changes to antihypertensive medication management. Communications between study pharmacists and prescribing physicians were not recorded; the true impact of the intervention may be underestimated.
Conclusion The significant and clinically important reduction in blood pressure observed in a randomized controlled trial was likely due to pharmacists’ changes in antihypertensive medication management rather than antihypertensive medication adherence. These observations support the addition of pharmacists to primary care teams that help patients with type 2 diabetes.
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