A Health Related Quality of Life Study in Patients with Acute Coronary Syndromes: The Cost-Effectiveness of Clinical Pharmacy Service in the Phase I, and Short Course Phase II Cardiac Rehabilitation Program Authors of proposal: 1, 2 Professor Dr. Sim Kui Hian, 4 Professor Dr. Mohd. Izham Mohd Ibrahim, 1, 2 Dr. Alan Fong Yean Yip, 3 Yanti Nasyuhana Sani, 3 Tiong Lee Len, 3 Bibi Faridha Mohd Salleh, 4 Dr Mohd. Azmi Ahmad Hassali, 4 Prof. Dr Yahaya Hassan, 3 Lawrence Anchah, 5 Karen Tang Siew Lang, 1 Hii Ai Ching,1 Sii Lik Ngoh 1 Dept of Cardiology, Sarawak General Hospital. 2 Clinical Research Centre, Sarawak General Hospital. 3 Dept of Pharmacy, Sarawak General Hospital. 4 School Pharmaceutical Sciences, Universiti Sains Malaysia. 5 Dept of Physiotherapy, Sarawak General Hospital. NIH Reference No.: (4) dlm.KKM/NIHSEC/08/0804/P07-161, dated 3rd September 2007 Completed 20th Dec 2009 Researcher: Lawrence Anak Ancah, B. Pharm, M. Clinical Pharm, Candidate for Ph.D Cinical Pharmacy in Cardiovascular & HRQoL

1. Pre Viva Presentation for CRP Study 2009 Data Presentation 1

2. A Health Related Quality of Life Study in Patients with Acute Coronary Syndrome: The Cost-Effectiveness of Clinical Pharmacy Service in the Phase I, and Short Course Phase II Cardiac Rehabilitation Program Mr. Lawrence AnakAnchah, 700713-13-5325 (Principal Investigator) Research Area: (FCA 701/ 48), Cardiovascular Pharmacy Reference No under NIH KKM: MRG-2007-11 Main Supervisor: Professor Dr. Mohamed Izham Bin Mohamed Ibrahim Field Supervisor and Co-Principal Investigator: Professor Dr. SimKuiHianMBBS(Hons)(Monash), FRACP, FACC, FCSANZ , FSCAI, FESC, FAPSIC, FAsCC, FCAPSC, FAHA, FAMM, FNHAM ,Head, Dept of Cardiology & Head, Clinical Research Centre (CRC), Sarawak General Hospital, MALAYSIA. Adjunct Professor, Faculty of Medicine & Health Sciences, University Malaysia Sarawak (UNIMAS) Co-Supervisor: 1. Dr. MohdAzmi Ahmad Hassali 2. Prof. Dr. Yahaya Hassan 2

3. Introduction Cardiac rehabilitation programs (CRP) has a different level of models and structures. Pharmacy Perspective: Phase I, in-patient CRP, and the outpatient phase II of CRP has poorly described in many articles elsewhere. The role of clinical pharmacy services in cardiology in Malaysia has been extensively evaluated since 2003. However, pharmacist’s involvement assemble in the interdisciplinary teamwork in the out-patient phase II CRP. Those services contain the intervention entity of counselling. 3

4. Aims & Design of Cardiac Rehabilitation Programs designed to limit physiologic and psychological effects of cardiac illness, ↓ risk for sudden death or reinfarction, control cardiac symptoms, stabilize or reverse atherosclerotic process, & enhance psychosocial and vocational needs of selected patients (USDHHS, 1995). CR services – comprehensive, long-term programs involving 1)medical evaluation, 2)prescribed exercise, 3)cardiac risk factor modification, 4)education and counseling 4

5. Significant of this study : Economic, Clinical and Humanistic Outcomes (ECHO), measurement of disease and therapeutic outcomes In this new model of CRP, will it be the most cost-effective or worthwhile effort for the administrators to implement the new role of clinical pharmacy service in cardiac rehabilitation? What is the major impact of outcomes that will be established from this collaborative practice and interdisciplinary teamwork by each health care provider in the phase I and short-course phase II CRP? Clinical Outcomes……Hospitalization, FLP improvement, BP, FBS, MACE reduction ECHO (Economic Clinical Humanistic Oucomes)…ICR 5

6. OBJECTIVES OF STUDY General Objective To determine the QoL outcomes in post ACS patients with interventional MCRP versus with the conventional CCRP To evaluate the impact of the clinical pharmacy collaboration practice in CRP in term of clinical outcomes and health-related outcomes. Specific Objectives To assess the cost effectiveness of the intervention relativeto other secondary prevention care programmes, effectivenesssuch as life years gained from the health care service perspective with the application of cost utility analysis approach. To investigate adherence to treatments. 6

7. Outline of CRP Phase I Inpatients Stage I (admission) Stage II Stage III (discharge) Phase II Outpatient 4-8 weeks program Phase III and Phase IV Community based or society based program 7

8. General Phases in CR Provision 8 Phase Iis the inpatient program that begins soon after a cardiac event (such as a heart attack, angioplasty, or a bypass surgery) and finishes when the patient is ready to go home from the hospital. The emphasis is on low-level exercise and education for the patient and family. Phase IIis an outpatient hospital-based program that begins approximately 2 weeks after discharge from the hospital. Dietitians, social workers, pharmacists, physicians, and others may also be involved in the care. This phase emphasizes monitored exercise and continued education on exercise and lifestyle management. Phase IIIis an ongoing community-based exercise and education program supervised by cardiac nurses and exercise specialists. Spouses and significant others may also participate in this maintenance program with a referral from a physician. Phase IVis a continuation of Phase III but without supervision. In this phase, the patients continue to apply what they have learned during the preceding phases.

9. Phase I, Stage I CRP (First assessment) 2004 Perth Royal Hospital, WA What we have learned from others and improve it. Phase I CRP Cardiac Care Unit, Sarawak General Hospital Ward rounding Pharmacist will identify those who needs counseling Stage I in counselling 9

10. Phase I, Stage II CRP (CTW) Bed side counselling regarding the evidence based medication Our target: IHD, UA, post MI, post PTCA, post CABG, HF and on warfarin Concomitant diseases/problems therapy (hyperlipidaemia, gout, DM, HPT, peripheral vessel disease, chronic AF….) Stenting (DES and BMS), double antiplatelets Medication and disease Medication adherence Self purchase (plavix), cardiprin RF Smoking cessation advise 10

11. Phase I, Stage IIIBed side and discharge counselling Preparation for Rx Screening and filling Medication discharge sheet (name, dose, frequency, duration, side effect, important notes) Counseling session and documentation in BHT CP1, 2 and 3 11

12. Phase II CRP in 2003-2008 Revolutionize the practice from forum to group counseling From common dissemination of knowledge to individualized counseling 12

13. Group counseling (The ideal) Talks in different languages Different in knowledge/educational levels Limitation More than one pharmacist Coordination with colleagues 13

14. Methodology Framework of Research METHODOLOGY AND MATERIALS 14

15. Participants: Admitted to CCU and CTW for recruitment +112 patients aged 25–70 years who were self-caring, literate and able to speak English/Malay/Dayak. Able to read or understand the Self-answered questionnaire Kuching based locality for Cardiac rehabilitation program Others are in control group and willing to be assessed for next 6 and 12 months follow-up Eagle KA et al. Guideline-Based Standardized Care Is Associated With Substantially Lower Mortality in Medicare Patients With Acute Myocardial Infaction. JAAC 2005;46(7):1242-8. Mehta RH, et al. Enhancing Quality of Care for Acute Myocardial Infarction: Shifting the Focus of Improvement From Key Indicators to Process of Care and Toll Use: J Am CollCardiol 2004; 43:2166-73. 15

16. Sample size In the study by Azman AB et al. on Malaysian general population using the SF-36, we derived the standard deviation from VT domains as δ = 17.68 and we wish to estimate the true mean to within 5 points with 95% confidence. Naing NN et al. 2003 guideline of estimation of sample size we derived; δ = 17.68, Δ = 5, and z = 1.96 n = (z δ /Δ) 2 = (1.96 X 17.68 / 5 ) 2 = 48.03 16

17. The criteria for inclusion and exclusion For CRP phase 2 ( 4 weeks) Post MI (ACS, NSTEMI, STEMI) PCI ( BMS, DES) Cardiothoracic—Bypass Will be longer in cardiac clinic for review and follow-up EXCLUSION Over 70 years old LVEF < 40%, high risk ?? compliance Other comorbidities- Aneurysm, ESRF, acute renal disease not resolve Logistic issue to follow-up, address?? Phone number??? 17

18. Pre-post nonequivalent groups quasi-experiment. not a randomized experiment Experimental design with multiple groups and multiple waves of measurement; lack of control. quasi-experimental design "nonequivalent" because in this design we do not explicitly control the assignment and the groups were nonequivalent 18

19. Screening and Recruitment process from Jan-Dec 2008 19

20. Study DesignMethodology Framework of Research 20

21. LOS, Demographic Baseline 21

22. LOS, days in CICU, CTW and CCU LOS Range (1 to 37 days) Median = 4, n=73, 22

23. Baseline during admission Demographic Data Mean Age from 3 groups Common complain Length of admission/stay ACS stratum commonly noted 23

24. 24

25. 25

26. Analysis of baseline finding 26

28. HPT

29. DM

30. Family

31. Smoking

32. Lipid

33. Age27

34. Risk Factor Non-LVSD Less than 25% are having 4-5 RF Majority 75%, 1-3 RF 28

35. Cardiac Enzymes during ACS event 29

36. The Prescribing Pattern for Secondary Prevention in ACS with or without Asymptomatic Left Ventricular Systolic Dysfunction 30

37. Anti Remodeling Medication: extreme least LVSD Non LVSD 31

39. EF of mean 58.14% (S.D. = 4.46)

40. 50% (n=7) were prescribed both ACEI & beta blockers

41. 50% were neither on ACEI nor ARBsNancy M. Recognizing and Managing Asymptomatic Left Ventricular DysfunctionCrit Care Nurse 2008. 28(2): 20-37 32

42. 33

43. Left Main Stenosis Based on the COROS and NCVD database 18.7 % in the LVSD group are having more than 50 percent occlusion at the LM However, those in NLVSD are negligible. May explained inconsistency in prescribing, example far less ACEI prescribed in NLVSD group. 34

44. Possible Finding & Discussion Possible causes are lack of recognition of LVSD when symptoms are not present clinically or Unwarranted fear of prescribing of vasoactive cardiovascular therapy (ACEI/ARB) to patients with LVSD in this study. Non LVSD is marginally less prescribed with ACEIs or ARBs Prescribing delay may due to BUSE level or due fear of hypotension with add on antihypertensive drugs. Nancy M. Recognizing and Managing Asymptomatic Left Ventricular DysfunctionCrit Care Nurse 2008. 28(2): 20-37 35

45. HR, BPS, BPD CLINICAL FINDING 36

46. FIGURE: Vital Sign: Heart Rate (hr1) noted during accident & emergency or the first reading while admittedThe control (group 3) and group 2, are mixed of those that referred to SGH and from A&E MCRP=1, CCRP=2, Control=3 The control (group 3) and group 2, are mixed of those that referred to SGH and from A&E 37

47. Vital Sign: Heart & BP after 12 months follow-up * Man-Whitney U Test 38

48. Hard End Point & Solf End Point after 12 months Follow-up 39

50. In control group only 20.93% (n=13) underwent CABG but refused or unable to join the CRP; therefore this data contribute less MACE analysis.

51. A lot of drop out in control group as we found that on 46.7% (n=29) were able to be contacted. Therefore, we will uncertain issues regarding their clinical outcomes.

52. Conclusion: Cardiac rehabilitation will cost more to health care provider but to certain extent . This it is because the operational cost that provided by clinician and the urgency of post ACS treatment .40

53. Lifestyle Counseling Skill among clinical Pharmacists & other health care providers This exploration study looking into the effectiveness of MCRP interventions to promote adherence to medications and inculcate knowledge of illness-treatment. Education Cardiac Patients & Spouse 41

54. FLP baseline for 3 groups at initial stage of admission, MCRP=12, CCRP=12, CONTROL=36 42

55. Pre and Post Cholesterol Finding 12 months follow-up 43

57. LDL reduction in MCRP of 0.709, and CCRP of 0.718, this greater improvement as compare with Control Group that only up to 0.298 Lauderdale, S. A (2005). Intensive Lipid-Lowering Therapy in Patients with Coronary Heart Disease. Ann Pharmacother, 39(2), 329-334. 44

59. Highly significant different was found in Intervention group (p<0.05) as compare with CCRP.

60. Cardiac Rehabilitation do have an element of education of diet and exercise to cater the risk factor of atherosclerosis among ACS cases. Pharmacist has a role to play on adherence to this endeavor.Conclusion: Highly intensive reinforcement of drug-education services in MCRP will greatly benefit to post ACS patients to reduce further on their total cholesterol level. 45

61. Cost Benefit and Cost-effectiveness QALY Utility Score Health Related Quality of Life 46

62. Measurement for Interventional Outcomes A patient perspective: quantitative surveys such as health status, work performance, symptom burden, and satisfaction. Health status can be measured using general or disease specific instruments General instrument measuring health-related quality of life (HRQoL) can assess patients’ perceptions of health status, thus derive the preference-based weights that can be used to calculate QALYs (Tradeoff in incremental costs and gains in health) Examples: SF-36, EQ-5D 47

63. EQ-5D 5 questions – each with 3 levels 5 health domains: pain, mood, mobility, self care and daily activities The EQ-5D utility score was computed using the algorithm by Dolan et al. a range from -0.594 to +1. 48

64. VAS within the 3 groups at during admission N=93, Range (20-100), Mean 59.29+ 18.57 Number of patients analysed, MCRP=12, CCRP=23, Control=33 49

65. SF-36 The SF-36 is a generic health questionnaire that measure eight dimensions (scales) of health status. Scores range from 0–100 Physical functioning (PF) Role limitation-physical (RP) Role limitation-emotional (RE) Social functioning (SF) Mental health (MH) Energy and vitality (EV) Bodily pain (BP), and General health perception (GH) Mental Component Summary scale (MCS) and a Physical Component Summary (PCS) scale Ware, EJ. SF-36 Health Survey: Manual and Interpretation Guide. Boston, Massachusetts , The Health Institute, New England Medical Center; 1993. p. 4:3. 50

66. 8 Domains of SF-36 n=97 51

67. Physical Component Summary (PCS) & Mental Component Summary (MCS) Oneway ANOVA: Post Hoc Multiple Comparisons, NS 52

68. PCS and MCS of SF-36 53

69. 54

70. 55

71. Intervention (MCRP) 56

72. Conventional Group (CCRP) 57

73. Conventional Group (CCRP) 58

74. Control Group 59

75. 60

76. Physical Component Summary (PCS) 61

77. Mental Component Summary (MCS) 62

78. Physical Function Domain Test & Analysis 63

79. Repeated Measure ANOVA: Mauchly’s Test 64

80. Tests of Between-Subjects Effects 65

81. Post-hoc tests (Using Tukey HSD) 66

82. Pairwise Comparisons of PF *. The mean difference is significant at the .05 level 67

83. Summary of PCS & MCS after 12 months 68

84. Utility Score from EQ5D Questionnaire 69

85. Finding There in remarkable improvement in physical ability in MCRP(30.36% for PF & 11.16% for PCS), and CCRP (34.33% for PF & 9.41% for PCS) as compare with Control Arm (17.57% for PF & 5.47% for PCS) In summary all the health components in have improve tremendously amongs patients who were recruited in rehabilitation program. The EQ5D utility measurement conclude that both MCRP and CCRP had a better score in utility tariff. 70

86. Knowledge and understanding of medication, 12-months observation 71

87. Know the indication Understanding the instruction given regarding their medication Know how to store their medication Know each name of medication prescriped 72

88. Summary of finding in knowledge of treatment regime and medication adherence 1. High score in understanding of instruction of how to use appropriately their medication in MCRP (p=0.022) 2. Most of patients in in CCRP and Control score poorly in understanding the name of each of their medications to treat their heart problems. Non-significant finding. 3. Remarkable number of poor knowledge of drug indication in CCRP and Control. Highly significant of score given in MCRP (p=0.005) 4. MCRP groups majority have shown high score in “knowledge of dose that they should take” (p=0.006) 5. All groups astonishingly have poor score in knowledge of how to store and keep their medication properly. 73

89. Management Perspective Cost Direct Cost QALY gained Cost-Utility of Intervention 74

90. Cost of health resource use during the 12-month follow-up Health resource Mean cost per patient conventional Mean cost per patient rehabilitation Incremental cost (rehabilitation minus conventional) DIRECT COST DRUG costs Pharmaceutical costs Test/laboratory costs Consultation costs/Time spent for phase I, II 75

91. Program Cost Costs of providing cardiac rehabilitation was calculated from the health care system perspective throughout a one-year period, The cost estimates include services typically for Length of stay during admission, During staff time during admission and providing phase 1 CRP, procedure salary* consumables, medications prescribed (example: syringes, catheter, gloves, drips, antibiotics, IV drugs, SK, Heparin, etc.) overheads and capital expenses (was not calculated due non-specific & segregated location in providing this intervention. Staff costs were based on the full-time equivalents that were required to conduct each protocol and educational sessions. MA Seldon*, P Joshi, YH Jong, HB Liew, TK Ong, KH Sim. Comparison and Cost-Effectiveness of CABG and PCI over One Year at SGH 76

92. 77

93. Costing for Medication Supply to Cardiology Department & Cardiothoracic Dept. 2008 78

94. Total cost by health care provider for per patient /day 79

95. 80

96. Costing for CABG and PCI (Bottom-up costing exercise; time consuming process) MA Seldon*, P Joshi, YH Jong, HB Liew, TK Ong, KH Sim. Comparison and Cost-Effectiveness of CABG and PCI over One Year at SGH 81

97. Investigation, Perfusion and other Interventions All groups analyzed in this study have shown non-significant different in in all investigation and intervention cost. 82

98. Cost of Medication on each ward according to LOS How much was spent for each patients in each ward 83

99. Cost of Admission according to Length of Stay 84

100. Health Care Provider Cost in treating post ACS for one year follow-up 85

101. Cost of Medication of ACS Annually(Start from admission until 12 months follow-up) * p&lt;0.05 86

103. More procedure was noted in the rehabilitation cases due to the fact that this is a quasi experimental design.

104. In control group (n=57), those was not diagnosed of STEMI (n=33) have higher tendency of not having any PCI procedure (p=0.031)

105. Conclusion : Cardiac rehabilitation will cost more to health care provider but to a certain extent . This it is because the operational cost provided by clinician and the urgency of post ACS treatment for stage PCI, follow-up CABG etc. We consider this incremental cost in medicines are not reflecting the true picture of operational cost of treatment87

106. 88

107. Estimation of the cost of treatment based expenditure (top-down), services, salary, hospital days, X2 =1.314, p= 0.518 89

108. High consumption of drugs/surgicals/investigations in a year in control group compare with MCRP and CCRP 90

109. Incremental Cost Ratio (ICR) of modified cardiac rehabilitation program is very minimum in term of operational cost for clinical pharmacy services. IC = Difference between the cost of program to the next best alternative program 91

110. Limitation Small sample size at the 12 months follow-up, though the remarkable improvement noted in quality of life components, with decrease number of data may have a high impact on data analysis to show the significant different. Long standing research should be implemented to identify a good data in qualitative research. Defaulters, drop-out and incomplete data set could have contributed to small number of data in 12-months follow-up. 92

111. General Conclusion Incremental Cost (IC) of having modified cardiac rehabilitation program have not shown any high implication of operational cost. What was known that intervention by clinical pharmacist was an extended role in cardiac care and equipped with well-documented protocol; time and commitment that’s count. Without any cardiac rehabilitation to post ACS patients, have a high impact to the cost of treatment annually. The Incremental Cost RM 837.68 OMT, RM 2,227.53 for PCI and RM 7,648.12 for Bypass Intensive lipid-lowering therapy reduces LDL-C levels to highly significant and more than conventional treatment . 93

112. Conclusion 1: Cardiac rehabilitation have remarkably improve all dimensions that contribute to health related quality of life (biopsycosocial perspective of health). However, in this study the modified Intervention rehabilitation program was not superior than the conventional program in term to improve QoL outcomes. Objective No. 1: To determine the QoL outcomes in post ACS patients with interventional MCRP versus with the conventional CCRP 94

113. General Conclusion……..(continue) Conclusion 2: Modified Cardiac rehabilitation and Conventional rehabilitation program appears toreduce cardiovascular morbidity and mortality (MACE) in patients whohave recently experienced ACS and up to the 12 months follow-up interlude Objectives No.2: To evaluate the impact of the clinical pharmacy collaboration practice in CRP in term of clinical outcomes and health-related outcomes. 95

114. Specific objectives: To assess the cost effectiveness of the intervention relativeto other secondary prevention care programmes, effectivenesssuch as life years gained from the health care service perspective with the application of cost utility analysis approach. To investigate adherence to treatments regimen. Conclusion 3: Incremental Cost Ratio (ICR) of modified cardiac rehabilitation program is very minimum in term of operational cost for clinical pharmacy services. MCRP can easily implemented in all hospitals and it is highly cost-effective program. Conclusion 4: Cardiac rehabilitation program with elements of clinical pharmacy services in phase I should be offer to all post ACS cases and it is proven has an add-on benefit reduction of total cholesterol, adherence to medical treatment plan, and remarkable improvement of knowledge of drugs usage (Instruction, Indication, & dosage taken). 96

116. 2. Medication adherence and understanding

117. 3. Structured intervention in Cardiac Care Unit (CCU) in phase1 stage 1 rehabilitation

118. 4. More emphasize the intensive counseling and motivation of phase I CRP by clinical pharmacists.97

119. Acknowledgement Pharmacy Department, SGH. Cardiology Department (CCU, CTW and Cardiac Clinic) USM, Penang. CRC, SGH Research team. 98

120. R&D Achievement 2008 99

121. R&D Achievement 2008 100

122. R&D Achievement 2009 Sarawak GH Presentations Done 101

123. Clinical Trials, Awards & others Awards: NCCR Conference 2009 Poster Competition: 1st Prize: Acute Coronary Syndrome Secondary Prevention Pharmacotherapy Prescribed at Discharge: The First National Multicentre Pilot Audit 1st Research Day SGH Poster Competition: 1st Prize: The Prescribing Pattern for Secondary Prevention in ACS with or without Asymptomatic Left Ventricular Systolic Dysfunction Insight from the CRP study: A single centre experience 2nd Prize: Factors Affecting Compliance on the Inhaler Corticosteroid Therapy in Outpatient Department: A Single Centre Experience 3rd Prize: Adherence Level Among Cardiac Patients by Using Self-Reported Morisky Score at SGH: A Single Centre Experience. On going Research Projects: 102

124. Thank You 103