1. Team-based Care to Improve Blood Pressure Control: The CAPTION Trial Barry L. Carter, Pharm.D., FCCP, FAHA, FASH, FAPHA The Patrick E. Keefe Professor in Pharmacy Department of Pharmacy Practice and Science College of Pharmacy and Professor Department of Family Medicine Roy J. and Lucille A. Carver College of Medicine University of Iowa

2. See Agenda Objectives

3. O r i g i n a l P a p e r A Cluster Randomized Trial to Evaluate Physician/Pharmacist Collaboration to Improve Blood Pressure Control Barry L. Carter, PharmD; George R. Bergus, MD; Jeffrey D. Dawson, ScD; Karen B. Farris, PhD; William R. Doucette, PhD; Elizabeth A. Chrischilles, PhD; Arthur J. Hartz, MD, PhD Funded by NHLBI: RO1 HL69801 Journal of Clinical Hypertension 2008;10:260-271 Cluster, Randomized Efficacy Trial

4. Collaborative Management of Hypertension Study: Efficacy Trial Only faculty / private physicians involved in the study. Patients 21-85 years with diagnosis of hypertension. Baseline BP: 145-179 SBP or 95-109 DBP for uncomplicated. 135-179 SBP or 85-109 DBP for diabetes. Clinic BP at 0, 2, 4, 6, 8, 9 months 24-hour BP at baseline and 9 months Journal of Clinical Hypertension 2008;10:260-271

5. Physician/Pharmacist Collaborative Management

6. Intervention Pharmacist conducted interview and assessed patient for strategies to improve BP control. Pharmacist made recommendations to MD and patient to improve BP control. Pharmacists and physicians worked to overcome/prevent sub-optimal treatment, clinical inertia, poor adherence, adverse reactions, drug interactions Pharmacists saw patients at least every 2 months x 9 months. NHLBI: RO1 HL69801

7. Data Analysis Continuous variables – likelihood-based mixed models with random patient effects fit to SAS Proc Mixed in an intention-to-treat analysis. Models adjusted for baseline BP, age, gender, race, education, insurance status, household income, marital status, smoking status, alcohol intake, BMI, number of co-existing conditions, baseline medication adherence and total number of visits during the study.

8. Baseline Demographics Control (n=78)Intervention (n=101) Age61.0 + 11.359.6 + 13.7* BP meds1.4 + 1.01.5 + 1.0 Baseline med adherence 88.6%71.1%* # co-existing DX0.46 + 0.780.47 + 0.81 Diabetes24.4%24.8% BMI (kg/m 2 )31.8 (+14.7)32.3 (+7.7) * - p < 0.001

9. Results * p<0.05, ** p<0.01, *** p<0.001, * ** *** ** * ** Carter BL, Bergus GR, Dawson et al. Journal of Clinical Hypertension 2008;10:260-271. Carter BL, Doucette WR. Franciscus CL, et al. Pharmacotherapy 2010;30:228-235. Sustainability

10. Results: BP Control Rates ControlInterven- tion Adjusted OR CI; p value All patients 52.9%89.1%8.93.8-20.7 P<0.001 Diabetes23.5%81.8%40.14.1-394.7 P=0.002 - Carter BL, Bergus GR, Dawson et al. Journal of Clinical Hypertension 2008;10:260-271. - Von Muenster SJ, et al. Pharmacy World & Science 2008:30:128-135. Main Finding: The major reason for the high control was due to intensification of medications.

11. Physicians accepted 95.8% of 267 pharmacist recommendations RecommendationFrequency by Visit 0 MoOpt2 Mo4 Mo6 Mo8 Mo9 Mo Added Thiazide n=454023000NA Added Other Drug n=79301318963NA Increased Dose n=89282114998NA Changed Dose Frequency n=7201310NA Switch Within Class n=15631320NA Decreased Dose n=14333230NA Drug Discontinued n=18248310NA Total n=2671114648292211NA BP Control Rate n=1010-52%67%73%84%89% Description of pharmacist interventions during physician-pharmacist co-management of hypertension. Pharmacy World & Science 2008:30:128-135.Von Muenster SJ, Carter BL, Weber CA et al. Description of pharmacist interventions during physician-pharmacist co-management of hypertension. Pharmacy World & Science 2008:30:128-135.

12. ORIGINAL INVESTIGATION Physician and Pharmacist Collaboration to Improve Blood Pressure Control Barry L. Carter, PharmD; Gail Ardery, PhD; Jeffrey D. Dawson, ScD; Paul A. James, MD; George R. Bergus, MD; William R. Doucette, PhD; Elizabeth A. Chrischilles, PhD; Carrie L. Franciscus, MA; Yinghui Xu, MS HEALTH CARE REFORM Trial Registration: clinicaltrials.gov Identifier: NCT00201019 Arch Intern Med. 2009;169(21):1996-2002 “Mixed” Efficacy-Effectiveness trial

13. Adherence Study: Combination of Efficacy and Effectiveness Prospective, cluster-randomized controlled trial in 6 community-based family medicine residency clinics all with clinical pharmacist faculty in the medical office. Research nurse in each clinic measured BP at baseline, 3 and 6 months and 24-hour BP at baseline and 6 months.

14. Intervention Pharmacist conducted interview and assessed patient for strategies to improve BP control. Pharmacist made recommendations to MD and patient to improve BP control. Pharmacists and physicians worked to overcome/prevent sub-optimal treatment, clinical inertia, poor adherence Pharmacists only encouraged to see patients at baseline and 1 month with a telephone call at 3 months with a goal to achieve BP control by 6 months (but they could see patients more often).

15. Research BP Measurement Automated Omron Device Measure 1 BP, record but do not use for research value Measure 2 BP values and average them if less than 4 mm Hg apart. If more than 4 mm different, measure a 4 th BP and average the 2 closest BP values (from the 2 nd to 4 th BP measurements).

16. Systolic Blood Pressure - p<0.001; **- p=0.0015; *** - p=0.0023 - p<0.001; **- p=0.0015; *** - p=0.0023 Arch Intern Med. 2009;169(21):1996-2002 Journal of Clinical Hypertension 2011;13:431-437. Retrospective evaluation of sustainability…

17. 17 Meta-analysis of Potency of individual components of team- based care Odds that BP was controlled (95% confidence Interval) Studies involving nurses1.69 (1.48-1.93) [69% increased chance] Studies involving pharmacists within physician offices or clinics 2.48 (2.05-2.99) [148% increased chance] Studies done in community pharmacies 2.89 (1.83-4.55) [189% increased chance] Carter BL, et al. Archives of Internal Medicine 2009; 169:1748-1755. Conclusion: All were effective but interventions by pharmacists appear to be more potent than by nurses.

18. C ollaboration A mong P harmacists and P hysicians T o I mprove O utcomes N ow ( CAPTION) Barry L. Carter, Pharm.D. Principal Investigator, CCC Department of Pharmacy Practice and Science, College of Pharmacy and Professor Department of Family Medicine Department of Family Medicine Roy J. and Lucille A. Carver College of Roy J. and Lucille A. Carver College of Medicine Medicine Christopher Coffey, Ph.D. Principal Investigator, DCC Professor and Director, Clinical Trials Data Management Center Management Center College of Public Health * The study is being funded by NHLBI/NIH, R01 HL091841-01A1.

19. Important Concepts that Determine Various Study Methodologies Implementation: is the process of putting to use or integrating evidence-based interventions within a specific setting. Sustainability: describes to what extent an evidence-based intervention can deliver its intended benefits over an extended period of time after external support from the donor agency is terminated. Rabin BA et al. A glossary for dissemination and implementation research in health. J Public Health Management Practice 2008;14:117-123.

20. CAPTION Study Outcomes Primary outcome = BP control @ 9 months (determined via research measurement) BP control defined as: < 140/90 for patients with uncomplicated hypertension < 130/80 for patients with diabetes or chronic kidney disease**

21. Outcomes (cont.) Secondary endpoints include: Mean BP @ 12, 18, 24 months

22. CAPTIONCAPTION 32 offices stratified by degree of pharmacy services and racial minorities: Then randomized to: 1. 1. Usual care group 2. 2.9-month pharmacist intervention 3. 3.24-month pharmacist intervention. Subjects followed for 24 months to determine: 1. 1.What happens when the intervention is stopped? 2. 2.Can the intervention be sustained for 2 years? 3. 3.Does the intervention benefit patients from minority groups?

23. Participating Locations

24. DemographicsDemographics Variable9 Month (N=194) N (%) 24 Month (N=207) N (%) Control (N=224) N (%) Total (N=625) N (%) p-value Female119 (61.3)125 (60.4)133 (59.4)377 (60.3)0.938 Age (SD) 60.6 (12.4)56.7 (11.8)60.5 (13.8)59.3 (12.8)0.055 BMI (SD) 33.8 (8.5)35.2 (9.0)32.9 (7.7)33.9 (8.5)0.090 DM or CKD * 102 (52.6%) 109 (52.7%) 103 (46.0%) 314 (50.2%) 0.5995 SBP (SD) 147.6 (13.7) 149.8 (15.6) 149.6 (15.3) 149.1 (15.0) 0.458 * - Required a lower treatment goal (<130/80) making it more difficult to achieve control

25. Pharmacist Interventions Group First 9 Months (rate/month) 9-24 Months (rate/month) 9 –Month Group 0.5760.074 24 – Month Group 0.5030.261

26. Primary Outcome 9-Month BP Control Variable Intervention Groups (N = 401) (N=226 minorities) Control Group (N = 224) (N=111 minorities) Model-Adjusted Difference – Intervention vs. Control (95% CI) p-value BP Control All subjects 43%34% 1.57 ( 0.99, 2.50 ) 0.052 BP Control Minorities 37%28% 1.54 ( 0.84, 2.81 ) 0.16 * - Defined as <140/90 for uncomplicated BP and <130/80 for diabetes or CKD

27. Provider Level Attitudes Variable9 Month (N=11) 24 Month (N=9) Control (N=12) p-value Pharmacy Structure Score *** Low High 3 (27%) 8 (73%) 3 (33%) 6 (67%) 4 (33%) 8 (67%) 1.00 Pharmacist TPB Mean (SD)21.0 (2.18) 21.8 (1.42)21.2 (3.89) 0.76 Physician TPB Mean (SD 19.8 (2.39)20.2 (1.56)17.4 (2.85) 0.02 TBP = Theory of Planned Behavior *** - There was a significant relationship between offices with higher PSC and better BP control, adjusted odds ratio and CI = 1.75 ( 1.23, 2.49 ), p = 0.002 *** - Subjects from sites with higher PSC had a mean lower SBP of 4 mm Hg (p=0.007) and 2 mm DBP (P=0.009)

28. Primary Outcome 9-Month BP Control When Adjusted for Baseline Pharmacy Structure Score Variable Intervention Groups (N = 401) (N=226 minorities) Control Group (N = 224) (N=111 minorities) Model-Adjusted Difference – Intervention vs. Control (95% CI) p-value BP Control All subjects 43%34% 1.52 ( 1.02, 2.29 ) 0.042 BP Minority Subjects 37%28% 1.54 ( 0.84, 2.81 ) 0.016 * - Defined as <140/90 for uncomplicated BP and <130/80 for diabetes or CKD

29. 9 – month BP- All subjects Variable Intervention Groups (N = 401) Control Group (N = 224) Model- Adjusted Difference – Intervention vs. Control (95% CI) p-value SBP Mean (SD) 131.6 (15.8) 138.2 (19.7) -6.07 ( -9.64, -2.50 ) 0.001 DBP Mean (SD) 76.3 (11.1) 78.0 (14.5) -2.89 ( -4.80, -0.99 ) 0.003

30. Results – Minority subjects Variable Intervention Groups (N = 226) Control Group (N = 111) Model Adjusted Difference – Intervention vs. Control (95% CI) p- value SBP Mean (SD) 133.0 (16.3) 140.3 (21.4) -6.42 ( -10.97, -1.87 ) 0.006 DBP Mean (SD) 77.9 (10.7) 78.8 (15.9) -2.98 ( -5.76, -0.20 ) 0.036

31. Systolic BP Results

32. BP Control Rates Results

33. Summary: Comparison Of Other Studies With CAPTION Mean difference (control group minus the intervention group) in SBP was -8 to -10 mm Hg in other studies and -6.1 mm Hg in CAPTION Mean difference in DBP was -3 to -6 mm Hg in other studies and -2.9 mm Hg in CAPTION While the effect was slightly less in CAPTION, the results were expected and very similar to other studies

34. Comments and Questions