Statin Utilization in Primary Prevention in Patients with Diabetes Mellitus in Hong Kong

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