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7/16/2010
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Diabetic Cardiology: Clinical Updates on Hypertension & Dyslipidemia Therapeutics
Vivian WY LeeAssociate ProfessorSchool of Pharmacy
The Chinese University of Hong Kong11 July, 2010
This Presentation covers:
• Hypertension and DyslipidemiaClinical updates
• Hypertension and diabetes • Dyslipidemia
Clinical Pharmacy Services in Hong
Kong
• AMPOULEPharmacy Innovation
Cardiovascular Risk Factors
Hypertension Cigarette smoking Inactivity
ADyslipidemia Obesity (BMI>30)
Age•>55 for men•>65 for women
Diabetes Mellitus
Microalbuminuria•Or GFR <60mL/min
Family History of Premature CVD•Men <55•Women <65
Introduction Hypertension: important modifiable risk factor for cardiovascular and renal
diseases
Healthy People 2010 (USA): Goal of 50% control rate
JNC-71: 30% unaware of diagnosis; 34% control rate
Hong Kong: 27.2% had hypertension, less than half aware; < 50% control rate 2,3,
Significance of BP Goal Attainment (JNC-71): 16mmHg in SBP associated with 60% in stroke and 50% in
CHD
Stage 1 Hypertension- 12mmHg in SBP X 10 years prevents 1 death in 11 patients
1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206-1252. 2. Population Health Survey 2003/2004. Comparative Project of Department of Health and Department of Community Medicine, University of Hong Kong 2005: i-ii.3. Cheung BM, Law FC, Lau CP. The Rule of Halves Applies in Chinese Hypertensive Patients. Am J Hypertens 2002; 15: 209A.
AB/CD Algorithm
ACEI/ARB Beta blocker
CCB Diuretics
Renin system: low vs. high
Compelling indications
IndicationIndication DiureticDiuretic --blockerblocker
ACEIACEI ARBARB CCBCCB Aldosterone Aldosterone antagonistantagonist
Heart failureHeart failure
Post MIPost MI
High CAD High CAD riskrisk
DiabetesDiabetes
Kidney Kidney diseasedisease
Recurrent Recurrent stroke stroke preventionprevention
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1. Sookaneknun P, Richards RME, Sanguansermsri J, et al. Pharmacist Involvement in Primary Care Improves Hypertensive Patient Clinical Outcomes. The Annals of Pharmacotherapy 2004; 38(12): 2023‐8.
2. Hanlon JT, Weinberger M, Samsa GP, et al. A Randomized, Controlled Trial of a Clinical Pharmacist Intervention to Improve Inappropriate Prescribing in Elderly Outpatients With Polypharmacy. The American Journal of Medicine 1996; 100: 428‐37.
3. Planas LG, Crosby KM, Mitchell KD, et al. Evaluation of a hypertension medication therapy management programme in patients with diabetes. Journal of the American Pharmacists Association 2009; 49(2): 164‐70.
4. Lee VWY, Leung PY. Glycemic Control and Medication Compliance in Diabetic Patients in a Pharmacist‐managed Clinic in Hong Kong. American Journal of Health‐System Pharmacy 2003; 60:2593‐6.
CLINICAL IMPACT OF PHARMACY OUTREACH
SERVICE (POS) IN COMMUNITY ELDERLY
PATIENTSPATIENTS
OBJECTIVES
To investigate the impact of POS in the management of hypertension and diabetes;
To evaluate the sustainability of POS beneficial effects
Study Design Prospective, uncontrolled, open labeled study
7 community elderly centres
Started in 2007, Ongoing
Participants
Inclusion Criteria Elderly centre attendees All subjects recruited in
2009 attended Summer Outreach Programme
All subjects recruited in
Exclusion Criteria
With cancer, psychiatric diseases, Parkinson’s or Alzheimer’s disease
All subjects recruited in 2008 included
Uncontrolled HTN1
Non-diabetes: ≥ 140/90 mmHgDiabetes: ≥ 130/80 mmHg
And / OrUncontrolled DM2
> 8mmol/L
Without chronic medications
On other clinical studies
Refusal
1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289(19):2560‐72.2. Chan JCN, Yeung VTF, Chow CC, Ko GTC, Cockram CS, Chan NN. A manual for management of diabetes mellitus: a Hong Kong Chinese perspective. 2nd ed. Hong Kong: Chinese University Press, 2005. p. 24.
Procedures
A total of 3 visits to each centre
Every 10 – 12 weeks
• July 2009 – Sept 20091
Summer Outreach ProgrammeSummer Outreach Programme
• Oct 2009 – Dec 20092
1st follow-up
• Jan 2010 – Mar 20103
2nd follow-up
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Compliance assessment
Disease knowledge assessment
Medication review
Body mass index measurement
Random capillary blood glucose measurement
Blood pressure measurement
Follow‐ups only
Blood pressure measurement
CounselingDrug indication, dosage, frequency, route and time
Goals of therapyDrug-drug/-food/-disease interactions
Adverse drug reactions
Drug storageLifestyle modifications
Disease management
Outcome Measurements
Primary Change in SBP and DBP
Secondary RCBG BMIBMI Compliance HTN, DM knowledge DRPs
Compare between baseline and latest visit Baseline → 1st visit to the subject Latest → last visit to the subject Baseline of disease knowledge, compliance → 1st follow-up
Demographic Data
Mean age = 77.01 ± 6.56
Male : female = 35:62 (36.08%:63.92%)
Age (n=97) Literacy (n=97)
14%
50%
36%
g ( )
60-69 yo70-79 yo≧80 yo
75%
25%
Literate
Illiterate
Demographic Data
Mean no. of chronic meds = 4.93 ± 2.43
Number of chronic medications (n=97)
Self‐purchased medicines / supplements (n=97)
8%8%
15%
13%
56%
1
2
3
4
≧5
17%
83%
Yes
No
Comparison between Subjects Recruited in 2008 and 2009
60%
70%
80%
90%
100%
Gender
85%
90%
95%
100%
Subjects recruited in 08 (n=40)
Subjects recruited in 09 (n=57)
Smoking
0%
10%
20%
30%
40%
50%
Subjects recruited in 08 (n=40)
Subjects recruited in 09 (n=57)
Female Male
Non/Ex‐smoker Current smoker
75%80%85%90%95%
100%
Subjects recruited in 08 (n=40)
Subjects recruited in 09 (n=57)
Drinking
Non/Ex‐drinker Current drinker
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Interventions Interviews per subject = 2.64
Duration of interview = 30.01 ± 8.37 mins No. of subjects with DRP(s) = 83 (85.57%) Referral notes to physicians issued = 20 (40% acceptance)
Referral notes to physicians
45%
30%
10%
5%5%
5%
p y
Medication change / Adverse drug reactions
Uncontrolled blood pressure
Uncontrolled blood glucose
Laboratory monitoring
Clarification on regimen
Replacement for expired drug
Blood PressureBlood Pressure
(mmHg), mean ± SDn Baseline Latest Difference
p value
AllSystolic
97152.38 ± 18.80 147.04 ± 20.72 ‐5.35 ± 22.42 0.021
Diastolic 73.84 ± 11.36 71.03 ± 10.97 ‐2.81 ± 10.49 0.010
Recruited Systolic40
149.31 ± 17.41 145.11 ± 23.93 ‐4.30 ± 25.40 0.290
in 200840
Diastolic 71.77 ± 9.23 69.59 ± 9.52 ‐2.47 ± 11.05 0.165
Recruited in 2009
Systolic57
154.54 ± 19.59 148.33 ± 18.35 ‐6.62 ± 20.53 0.017
Diastolic 75.30 ± 12.52 72.00 ± 11.83 ‐3.16 ± 10.13 0.021
Goal Attained, n(%) n Baseline Latest Difference p value
All 97 14 (14.43) 22 (22.68) +8 (+8.25) 0.096
Recruited in 2008 40 9 (22.5) 10 (25.00) +1 (+2.50) 1.000
Recruited in 2009 57 5 (8.77) 12 (21.05) +7 (+12.28) 0.039
Blood Pressure – Sustainability
110
130
150
170
190
c Blood Pressure
(mmHg)
Change of Systolic Blood Pressure throughout the 2‐year Study
08/09 1st
08/09 2nd
08/09 3rd
08/09 4th
08/09 5th
08/09 6th
09/10 1st
09/10 2nd
Systolic
Visit
Start of 2008/09 End of 2009/10 Difference p value
Blood Pressure (mmHg)Systolic, mean ± SDDiastolic, Mean ± SD
166.40 ± 20.2279.18 ± 11.79
145.01 ± 23.6369.30 ± 9.57
‐21.39 ± 24.72‐9.88 ± 13.48
<0.001<0.001
Goal Attained, n (%) 0 (0.00) 10 (25.00) 10 (+25.00) 0.002
Random Capillary Blood Glucose
Random Capillary Blood Glucose, mean ± SD
n Baseline Latest Difference p value
All 97 8.41 ± 4.22 8.23 ± 3.96 ‐0.18 ± 4.23 0.670
Goal Attained, n(%) n Baseline Latest Difference p value
All 97 57 (58.76) 59 (60.82) +2 (+2.06) 0.860
Random Capillary Blood GlucoseChange of Random Capillary Blood Glucose throughout the 2‐year Study
0
2
4
6
8
10
12
14
16
m Capillary Blood Glucose
(mmol/L)
30%
35%
40%
45%
50%
55%
60%
At‐goal Rate
0
08/09 1st
08/09 2nd
08/09 3rd
08/09 4th
08/09 5th
08/09 6th
09/10 1st
09/10 2ndR
andom
Visit
30%
08/09 1st
08/09 2nd
08/09 3rd
08/09 4th
08/09 5th
08/09 6th
09/10 1st
09/10 2nd
Visit
Start of 2008/09 End of 2009/10 Difference p value
Random Capillary Blood Glucose (mmol/dL)
8.86 ± 3.46 9.02 ± 4.14 +0.16 ± 5.25 0.848
Goal Attained, n (%) 14 (35.00) 22 (55.00) +8 (20.00) 0.096
Hypertension KnowledgeHypertension
Knowledge Score, mean ± SD
n Baseline Latest Difference p value
All 91 6.12 ± 2.14 6.96 ± 1.87 +0.84 ± 1.65 <0.001
Recruited in 2008 37 6.32 ± 2.36 7.24 ± 1.92 +0.92 ± 1.52 0.001
R it d i 2009 54 5 99± 2 01 6 77± 1 82 0 78± 1 74 0 002
Change of Hypertension Knowledge Score
Recruited in 2009 54 5.99 ± 2.01 6.77 ± 1.82 +0.78 ± 1.74 0.002
Recruited in 2008 (n=37)
Recruited in 2009 (n=54)
Difference p value
Hypertension Knowledge, mean ± SD
6.32 ± 2.36 5.99 ± 2.01 0.33 ± 0.46 0.470
Baseline Hypertension Knowledge Score of Subjects Recruited in 2008 and 2009
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Diabetes KnowledgeDiabetes
Knowledge Score, mean ± SD
n Baseline Latest Difference p value
All 44 6.89 ± 2.34 7.82 ± 2.05 +0.93 ± 1.39 <0.001
Recruited in 2008 22 7.39 ± 2.30 8.41 ± 2.03 +1.02 ± 1.19 0.001
R it d i 2009 22 6 39± 2 31 7 23± 1 94 0 84± 1 59 0 022
Change of Diabetes Knowledge Score
Recruited in 2009 22 6.39 ± 2.31 7.23 ± 1.94 +0.84 ± 1.59 0.022
Recruited in 2008 (n=22)
Recruited in 2009 (n=22)
Difference p value
Diabetes Knowledge, mean ± SD
7.39 ± 2.30 6.39 ± 2.31 1.00 ± 0.70 0.158
Baseline Diabetes Knowledge Score of Subjects Recruited in 2008 and 2009
Drug-related Problems
4%
4%2% 2%
Identified DRP (n=233)
Non‐compliance
Suspected adverse drug reaction
Dosage too low 6%
2%
1%
1%
Noncompliance Identified (n=147)
Misunderstood directions
Missed doses
Fear of adverse d ti
63%10%
10%
5%
4%
Drug storage problem
Need additional drug
Possible interactions
Ineffective drug
Others
61%12%
9%
8% drug reaction
Inappropriate administration
Think no need
Inappropriate pill splitting method
Overuse as needed (PRN) drugs
Drug-related ProblemsNon-compliance: Missed dose
Forgetfulness
Complex regimen
A i i 80 1TAB QDGlibenclamide 5mg
Aspirin 80mg 1TAB QDMethyldopa 250mg 1TAB BDFamotidine 20mg 1TAB BDCarvedilol 6.25mg 1TAB BDIsosorbide dinitrate 15mg 1TAB TIDEnalapril 10 mg 1TAB OMFluvastatin 80mg 1TAB Nocte
g2TAB AM and 1.5TAB PM
Compliance aids may help1,2
1. Ruppar TM, Conn VS, Russell CL. Medication Adherence Interventions for Older Adults: Literature Review. Research and Theory for Nursing Practice: An International Journal 2008; 22(2): 114‐147.
2. Petersen ML, Wang Y, Van der Laan MJ, et al. Pillbox Organizers Are Associated with Improved Adherence to HIV Antiretroviral Therapy and Viral Suppression: A Marginal Structural Model Analysis. Clinical Infectious Diseases 2007; 45:908–915.
Colour coding Labels Labels with different colours distinguishing different type
of drugs
Labels indicating different time of administration
Completed Drug Diaries Pill Boxes Help elderly with problem of forgetting doses due to
complex drug regimen
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Conclusions
Pharmacy Outreach Service with pharmacist interventions once every 10-12 weeks improved BP control, disease knowledge in elderly with uncontrolled HTN and/or DM.
The beneficial effect of POS is sustainable with regular follow-up visits.
H li id iHyperlipidemia
LIPOPROTEINS
Chylomicrons
Very Low Density Lipoprotein (VLDL-C)
Intermediate Density Lipoprotein (IDL-C)
Low Density Lipoprotein (LDL-C)
High Density Lipoprotein (HDL-C)
Emerging Risk Factors for CHD
Lipoprotien (a) LDL-like moiety + large glycoprotein, Apo (a) Competes with plasminogen for fibrin binding sites---inhibit
fibrinolysis Ability to promote LDL oxidation and inflammation within Ability to promote LDL oxidation and inflammation within
the injured epithelium Has not been shown to respond to dietary fat restriction,
weight loss, or exercise Use of either estrogen or niacin
Homocysteine
By-product of the metabolism of methionine
Require several enzyme and vitamin cofactors, including folic acid, vitamin B12 & B6 for metabolism
Promotion of foam cell formation, LDL oxidation, platelet aggregation, and endothelial dysfunction
Normal level: 5-15 mol/L
Lowered by lifestyle modifications & increasing intake of folic acid, vitamin B12 or B6
C-reactive Protein
An acute phase reactant that is a sensitive marker for systemic inflammation
CRP elevated---at risk for future atherosclerotic events
Microinflammation may cause a stable plaque to rupture and become unstable
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Small, dense LDL Particles
More susceptible to oxidation
Less likely to bind to LDL receptors
Slowly eliminated from plasma
Can easily gain access into the arterial wall due to its small y gsize
Commonly found in patients with hypertriglyceridemia and low HDL
Abnormal subclass (Pattern B) can be treated with niacin or fibric acid derivatives
improved glycemic control
weight loss
CHD Risk Reduction with Lipid Level Changes
Type of Lipid Lipid Level Changes
CHD Risk Reduction
LDL-CLow-density lipoprotein cholesterol
0.026 mmol/L 1 %
cholesterol
TCTotal cholesterol
0.06 mmol/L 2 to 3 %
HDL-CHigh-density lipoprotein cholesterol
0.026 mmol/L 3 %
Source: Holme (1993), Brewer 2004
National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III
CHD Risk Category Minimal LDL-C Goal (1)
Optimal LDL-C Goal (2)
High RiskCHD or CHD risk equivalent , 10-year CHD risk > 20%
< 2.6 mmol/L < 1.8 mmol/L
d l i h i k 3 4 l/ 2 6 l/Moderately High Risk2+ risk factors,10-year CHD risk 10 to 20%
< 3.4 mmol/L < 2.6 mmol/L
Moderate Risk2+ risk factors,10-year CHD < 10%
< 3.4 mmol/L -
Low Risk0 – 1 risk factor
< 4.1 mmol/L -
(1) NCEP ATP III 2001, (2) Grundy et al 2004
Clinical Impact of Clinical Pharmacy Services on
Hyperlipidemia Management –H K E iHong Kong Experience
Chung JS, Lee KKC, Tomlinson B, Lee VWY. Journal of Cardiovascular Pharmacology and Therapeutics ( In press)
Objective of Study
To evaluate the clinical benefits of apharmacist clinical service for themanagement of hyperlipidemia in anambulatory setting of public hospitalin Hong Kong
Methodology of Study
Chinese patients > 18yearsMale or Female
History of hyperlipidaemia or CHD
Approved by the Clinical Research Ethics Committee of CUHKOutpatient Lipid Clinic, Prince of Wales Hospital
24-months study period
Control Group Intervention GroupControl Group(n = 150)
Routine Physician Care
Intervention Group(n = 150)
Routine Physician CarePharmacist Intervention
Educational Visits (every 16 to 26 weeks)
Monthly Telephone Follow-Ups
CHD risk assessment (Framingham point scores), Lipid profilereviews (NCEP ATP III 2001), Healthy lifestyle advice, Drugeducation, Medication compliance via pill-counting, Additional adviceon comorbidities
Both Groups: Validated Questionnaire Survey on
CPS Implementation before and after study.
Physicians’ view of CPS
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Demographic Data
Characteristics Intervention Group (n = 150)
Control Group
(n = 150)
P value
( ) ( ) ( ) ( )Age (years), mean (SD) 56.2 (10.4) 57.9 (12.9) ns
Sex (male), n (%) 68 (45.3) 60 (40.0) ns
Hypertension, n (%) 76 (50.7) 78 (52.0) ns
Diabetes mellitus, n (%) 40 (26.7) 43 (28.7) ns
Hypertension & Diabetes mellitus,n (%)
29 (19.3) 30 (20.0) ns
Lipid Profile Changes in Intervention and Control Groups Before & After the Study
Intervention Group(n = 150)
Control Group(n = 150)
BaselineMean (SD)
End of StudyMean (SD)
BaselineMean (SD)
End of StudyMean (SD)
LDL-C (mmol/L)
3.53 (1.30) 2.60 (0.89) 3.48 (1.35) 3.04 (1.17)
(mmol/L)
HDL-C (mmol/L)
1.60 (0.41) 1.72 (0.46) 1.63 (0.50) 1.69 (0.55)
TC (mmol/L)
6.05 (1.41) 5.00 (0.93) 5.91 (1.27) 5.52 (1.26)
TG (mmol/L)
2.20 (1.72) 1.54 (1.06) 2.08 (1.24) 1.84 (1.57)
Low-density lipoprotein cholesterol (LDL-C), High-density lipoprotein cholesterol (HDL-C), Total cholesterol (TC),Triglycerides (TG)
Comparison of Lipid Profile Changes between Intervention & Control Groups at end of study
Mean % ChangeIntervention
Group (n = 150)
Mean % Change Control Group
(n = 150)
P value
LDL-C (mmol/L) - 23.63 (0.12) - 3.71 (0.40) < 0.001LDL C (mmol/L) 23.63 (0.12) 3.71 (0.40) 0.001
HDL-C (mmol/L) + 8.83 (0.14) + 4.74 (0.10) ns
TC (mmol/L) - 15.25 (0.10) - 5.20 (0.12) < 0.001
TG (mmol/L) - 22.33 (0.16) - 2.70 (0.33) < 0.001
Low-density lipoprotein cholesterol (LDL-C), High-density lipoprotein cholesterol (HDL-C), Total cholesterol (TC),Triglycerides (TG)
Potential CHD Risk Reduction in Study
Mean Reduction Potential CHD Risk Reduction
Control Group
LDL C level 0 44 mmol/L 16 9%LDL-C level 0.44 mmol/L 16.9%
Intervention Group
LDL-C level 0.93 mmol/L 35.8%
Summary
Overall lipid mean reduction was more in intervention group LDL-C level 7 times more than control group TC level 3 times more than control group TG level 10 times more than control groupg p
Control group showed a lipid-lowering effect with current hyperlipidaemic management
Addition of pharmacist improved lipid-lowering effect further and more patients achieved LDL-C goals
http://www.pharmacy.cuhk.edu.hk/ampoule/
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http://www.pharmacy.cuhk.edu.hk/ampoule/
TEAM WORK
Acknowledgement
Collaborators Prof. Brian Tomlinson (Department of Medicine & Therapeutics, CUHK) Dr. Celeste Ewig (School of Pharmacy, CUHK) Pharmaceutical Society of Hong Kong CUHK School of Pharmacy Alumni Association Sik Sik Yuen Ho Chui District Community Centre for Senior Citizens;
Sh K H i W lf C il Ch k Y C M ti Di t i t Eld l C it Sheng Kung Hui Welfare Council Chuk Yuen Canon Martin District Elderly Community Centre and Sheng Kung Hui Welfare Council Wong Tai Sin District Elderly Community Centre;
Yang Memorial Methodist Social Service Choi Hung Community Centre for Senior Citizens;
Tseung Kwan O Aged Care Complex – Jockey Club District Elderly Community Centre Vicwood K. T. Chong Neighbourhood Elderly Centre Social Welfare Department, Hong Kong Special Administrative Region
Funding Agency Knowledge Transfer Project Fund, University Grant Committee
Thank You!