Statin Utilization in Primary Prevention in Patients with
Diabetes Mellitus in Hong Kong
Vivian Lee, Pharm.D.
Assistant Professor
School of Pharmacy
The Chinese University of Hong Kong
Disease Prevalence and Risk
Prevalence & incidence of diabetes mellitus (DM) in HKDM pts has 2-4 fold increase risk of developing CHD & strokeDM = Coronary heart disease (CHD) risk equivalent*
10-yr risk of CHD >20%Low-density lipoprotein-cholesterol (LDL) goal for high-risk <2.6mmol/L
Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) JAMA 2001;285:2486-2497.
Significance of this study
Use of primary prevention in diabetic patients is still suboptimal in local practice
Portion of patients attaining target LDL (<2.6mmol) is lowObserved reluctance among physicians in titrating up dosages of statins
Findings of this study are helpful in promoting rational use of statin therapy
Objectives
Studying the role of statins in primary prevention of cardiovascular diseases in DM patients in HK
Comparing the treatment outcomes in DM patients taking statins vs no statins
Describing the resources utilization in DM patients prescribed statins
Methods
Retrospective chart reviewStudy sites: RH & TWEH, 2 public hospitals in HKInclusion
DM, no history of CHD/strokeF/U at RH/TWEH during 2002/03With (study group) or without (control group) lipid-lowering agent (LLA)
ExclusionCHD, MI, stroke, severe HF, angina, peripheral vascular diseaseLong-term disease (e.g. cancer, severe chronic airway disease)
DM pts F/U at RH/TWEH during 2002/03
Pts with no h/o CHD (primary prevention)
Pts with h/o CHD (secondary prevention excluded)
Review medical charts
Pts on LLA (study group)
Pts not on LLA (control group)
LLA= lipid lowering agent
Methods
Primary outcomeCV events (MI, CHD, stroke)
Secondary outcomeAll-cause mortality
Methods
Investigation parametersProportion of pts taking statins
Cholesterol levels
Proportion of pts attaining cholesterol goal(i.e. <2.6mmol/L)
Choices of statins & dosage
Adverse drug effects related to statins
Occurrence of primary outcomes
Results
Patient Recruitment
DM patients (n 1000)
Hx of CHD / stroke (n = 310) Hx of CHD / stroke (n = 681)
Excluded
Chart a/v (n = 222)Chart n/a (n = 88)
Excluded
On LLAs (n = 75) Not on LLAs (n = 147)
Patient Demographics
Baseline features
On LLAs
(n = 75)
Not on LLAs (n = 147)
P-value
Age (years) 67.2 (±12.7) 68.0 (±16.2) <0.05
Men 35 (46%) 75 (51%) <0.05
Smoking
Never 47 (62%) 115 (78%)
Ex-smoker 14 (19%) 20 (14%) <0.05
Current 14 (19%) 12 (8%) <0.05
Past Medical History
Diagnosis On LLAs
(n = 75)
Not on LLAs
(n = 147)
Diabetes (Type 1) 3 (4%) 7 (5%)
Hypertension 70 (93%) 132 (90%)
Dyslipidemia 26 (34.7%) 7 (4.8%)
Congestive heart failure
9 (12%) 3 (2%)
Cardiac arrhythmias 4 (5.3%) 3 (2%)
Past Medical History
Under-diagnosis of dyslipidemia:
For patients not on LLAs:49.0% patients had LDL-C > 2.6 mmol/L
Among them, 40.3% had LDL-C > 3.4 mmol/L
Patients were deprived of lipid-lowering treatment!
Blood Pressure Control
Blood Pressure
On LLAs
(n = 75)
Not on LLAs
(n = 147)
P-value
SBP < 130 13 (17.3%) 26 (17.7%) <0.05
Worse BP control in the LLA group
Glycemic Control
Blood Glucose
On LLAs
(n = 75)
Not on LLAs
(n = 147)
P-value
HbA1c 7.71 (±1.45) 7.60 (±1.50) <0.05
HbA1c < 7 16 (21%) 34 (23%) <0.05
Worse glycemic control in the LLA group
Concurrent Medications
Medications On LLAs
(n = 75)
Not on LLAs
(n = 147)
Metformin 53 (71%) 101 (69%)
Insulin 28 (37%) 40 (27%)
Antiplatelet/
anticoagulant
33 (44%) 28 (19%)
ACEI/ARB 50 (67%) 80 (54%)
Beta Blockers 16 (21%) 35 (24%)
Use of Lipid-lowering Agents
Simvastatin , 36%
Atorvastatin ,29%
Fluvastatin , 19%
Gemfibrozil ,13%
Cholestyramine ,3%
Use of Lipid-lowering AgentsDrug (Daily doses) No. of patients %
Atorvastatin
10 mg 17 22.67
20 mg 5 6.67
Fluvastatin
20 mg 3 4.00
40 mg 10 13.33
60 mg 1 1.33
Simvastatin
5 mg 7 9.33
10 mg 16 21.33
20 mg 4 5.33
Use of Lipid-lowering Agents
Drug (Daily doses) No. of patients %
Gemfibrozil
600 mg 5 4.00
1200 mg 7 9.33
Cholestyramine
12 gm 2 2.67
Dosage Titration of Lipid-lowering Agents
Majority (n = 32, 68%) were maintained on the same dose.
A very small number (n = 4, 5%) had their dosages titrated upwards.
Laboratory Assessments of Lipid Levels
No lipid levels within the 2-year study period:
On LLAs: n = 9 (12%)
Not on LLAs: n = 49 (33%)
Inadequate Laboratory Monitoring!
Laboratory Assessments of Lipid Levels
Lipid panel (mmol/L)
On LLAs
(n = 75)
Not on LLAs
(n = 147)
P-value
TC 5.51 4.83 <0.05
LDL-C 3.10 2.88 <0.05
HDL-C 1.21 1.37 <0.05
TG 1.48 1.21 <0.05
Laboratory Assessments of Lipid Levels
0
1
2
3
4
5
6
TC LDL-C HDL-C TG
Lipid Panel
On LLAs
Not on LLAs
Laboratory Assessments of Lipid Levels
Drug No. of patients No. of patients reaching LDL target
Atorvastatin 22 (29%) 6 (27%)
Fluvastatin 14 (19%) 4 (29%)
Simvastatin 27 (36%) 9 (33%)
Gemfibrozil 10 (13%) 1 (10%)
Cholestyramine 2 (3%) 1 (50%)
Treatment Outcomes
Primary outcome On LLAs
(n = 75)
Not on LLAs
(n = 147)
P-value
Primary Outcomes
MI 7 (9.3%) 6 (4.1%)
CHD 1 (1.3%) 7 (4.8%)
Stroke 4 (5.3%) 2 (1.4%)
TOTAL 12 (15.9%) 15 (10.3%) <0.05
Secondary Outcomes
All-cause mortality 5 (6.7%) 6 (4.1%) >0.05
Treatment Outcomes
0.00%
2.00%
4.00%
6.00%
8.00%
10.00%
Myocardial
infarction
Coronary heart
disease
Stroke All-cause
mortality
On LLAs
Not on LLAs
Adverse Drug Reactions
Elevation in liver transaminases reported in 7 patients (9.3%)
Myopathy reported in one patient (1.3%)
Otherwise well-tolerated
Conclusion
Diabetic population is at high risk of CV complications
Majority had unsatisfactory LDL levelsLess than 40% received primary preventionBenefits of primary prevention was not well recognized in local practice
Problems in prescribing Under-dosing of LLALack of laboratory monitoring of cholesterol levelsPatients’ non-compliance
Need to establish and promote appropriate primary prevention in diabetic population