Transcript Cost-effectiveness of atorvastatin 10 mg daily in the

Cost-effectiveness of atorvastatin 10 mg daily in the primary prevention of major
cardiovascular events in patients with type 2 diabetes in Canada
H. Khoury1, M. Wagner1, E. Merikle2, S.J. Johnson3, C. Roberts4
Consultants inc, Montreal, QC, Canada; 2At the time of the study: Pfizer Canada Inc., Montreal, QC, Canada; Current affiliation: Center for Health Outcomes Research, United BioSource Corporation, Montreal, Canada;
3Analysis Group Inc., New York, NY; 4Global Outcomes Research, Pfizer Inc., New York, NY
Background
 In Canada, the prevalence of cardiovascular disease (CVD) is five-fold higher in individuals
with diabetes than those without.1
 To reduce the risk of cardiovascular (CV) events, the Canadian Diabetes Association
recommends aggressive lipid management involving statin therapy for high-risk patients to
reach and maintain low density lipoprotein cholesterol (LDL-C) level below 2.5 mmol/l, and
total cholesterol to high density lipoprotein cholesterol ratio (TC:HDL-C) below 4.0.2
 The Collaborative Atorvastatin Diabetes Study (CARDS), a double-blind randomized
controlled trial conducted in the UK and Ireland, explored primary prevention of CV events
with atorvastatin 10 mg daily in 2,838 patients with type 2 diabetes and no previous history
of coronary heart disease (CHD), with at least one other CVD risk factor, and baseline LDLC levels ≤ 4.14 mmol/l.3
 Over a 3.9-year follow-up period, CARDS demonstrated that atorvastatin 10 mg daily
achieved significant reduction of primary CV events (relative risk [RRR] vs placebo: 0.37;
95% CI: 0.52 to 0.17; P=.001), and also reduced all-cause mortality (RRR:0.27; 95% CI:
0.48–1.0; P=.059).3
 The CARDS Health Economic Model—a Markov-type decision analytic model of primary
prevention designed to predict long-term outcomes—demonstrated that atorvastatin was
cost-effective and improved clinical outcomes in US patients with type 2 diabetes and at
least one other CVD risk factor.4
Remain Well
Well
Event Survive
Primary CHD Event
Event Death
Well
Primary Stroke Event
Stroke Survive
Stroke Death
Other Death
Remain Event History
Secondary CHD Event
Atorvastatin 10 mg
Event
History
Second Event
History
Remain Second
Event History
Other Death
Event Survive
Stroke Survive
Other Death
Second Event History
Other Death
Event Death
Other Death
Placebo
Objective
To assess the clinical and economic benefits of atorvastatin 10 mg daily in Canadian patients
with type 2 diabetes without established CHD and with at least one other CVD risk factor,
from a Ministry of Health perspective, using the CARDS Health Economic Model.
Methods
 The CARDS Health Economic Model predicts the incidence of CV events (CHD and
stroke), total costs, survival and quality-adjusted life years (QALYs) (Figure1).
 The model followed a hypothetical cohort of Canadians with type 2 diabetes and no
documented history of CVD, with at least one other CVD risk factor, over 5, 10, and 25-year
time horizons.
 Annual transition probabilities for primary events were derived from the United Kingdom
Prospective Diabetes Study (UKPDS) risk equations,5,6 and the CARDS trial.7 The risk of
having a second event was increased to reflect the increased CVD risk for patients with
diabetes with a prior myocardial infarction (MI).8
 Hazard ratios (HR) were taken from the CARDS trial.3
 Adherence rate: 100% for the 1st yr, adjusted to reflect decreasing rates from the CARDS
trial3 during the first 4 yrs, and kept constant after 4 yrs.
 Acute CVD-related mortality rates were based on the CARDS trial.3 Mortality due to causes
other than CVD were taken from 2005 life tables for Canada.9
 Utility scores were obtained from a cross-sectional sample of the National Population
Health Survey in Canada.10
 Resource utilization and costs: Canadian cost for atorvastatin was obtained from the
Ontario Drug Benefit formulary (ODBF);11 drug cost was reduced by 50% after the 4th yr to
account for genericization of atorvastatin. Acute care cost of stroke and aggregate acute
care cost of CHD events (angina, MI, coronary artery bypass graft (CABG), percutaneous
coronary interventions (PCI) with and without stent, and cardiac catheterization) were
obtained from the Ontario Case Costing Initiative (OCCI) Acute Inpatient Cost 2003/04
database.12 Subsequent year costs for stroke and CHD (aggregate cost of MI and angina)
were estimated based on O’Brien et al.13
 Costs and benefits were discounted by 5%.14
 One-way deterministic (tornado diagram) and probabilistic (acceptability curve) sensitivity
analyses (SA) were conducted to assess model uncertainty.
Event Death
Event History
Event Death
Event History
Stroke Death
Other Death
Event History
Other Death
Event Death
Secondary Stroke Event
CARDS
Canadian
cohort
3
Results
Figure 1: Markov analytical model
Table 1: Base-case input parameters
Baseline characteristics of Canadians with type 2 diabetes and no
previous CHD
Age,16 yrs
61
Disease duration,17 yrs
8.1
Women,18 %
48
19
Atrial fibrillation, %
4.7
Afro-Caribbean,20 %
2.2
16
Current smoker, %
16.1
HbA1c,21 %
8.3
Systolic blood pressure,16 mm Hg
130
TC,22 mmol/l
4.9
HDL-C,23 mmol/l
1.1
Baseline incidence, events/year
CHD6
0.01120
5
Stroke
0.00186
Event probabilities
1st yr baseline probability in placebo*
CHD
0.0154
Stroke
0.0055
HR associated with 10 mg atorvastatin†
CHD
0.660
Stroke
0.590
Probability of death3
CHD event
0.273
Stroke event
0.107
Relative risk8
CHD secondary event
2.22
Stroke secondary event
1.89
10
Utilities, mean
Well/baseline
0.76
CHD
-0.03
Stroke
-0.16
Costs
2007 Can$
First year costs
Atorvastatin 10 mg/day11
607
Stroke event12
17,106
CHD procedures and medical admission-based
12,365
events‡
Subsequent (post-event) year costs
Atorvastatin 10 mg/day, up to 4th year (pre-generic)11
607
Atorvastatin generic drug after 4th year§
285
Stroke event (non-fatal) history
10,137
CHD event history**
1,444
CHD: coronary heart disease; HbA1c: glycated hemoglobin, HDL-C: high density lipoprotein-C; total cholesterol
* Based on Canadian patient characteristics and patients of the UKPDS model 24
†
Based on patient-level CARDS trial data3
‡
Total average cost of any CHD intervention (angina, MI, CABG, PCI with or without stent, cardiac catherization) weighted by the frequency of
12
utilization of each intervention from the OCCI database
Second Event History
Event Death
1
Base-case results
 Over 10 yrs, patients treated with atorvastatin experienced fewer CV events, gained 0.07
QALYs/patient, and had 2% fewer deaths compared with placebo, at an additional cost of
Can$922/patient.
 Incremental costs decreased considerably over time despite the increase in drug costs,
most likely as a result of decreased medical costs associated with fewer cardiac events.
 The incremental cost-effectiveness of atorvastatin was Can$12,687/QALY [95% CI
dominant–$66,048] at 10 yrs, Can$1,362 [dominant–$49,432] at 25 yrs (lifetime analysis),
and Can$70,773/QALY [33,981–195,914] at 5 yrs.
Second Event History
Event Death
Atorvastatin 10 mg daily
Base case results: 10-year horizon
Clinical outcomes per patient*
Number of CV events (CHD & stroke)
Life years gained
QALYs
Death (all-cause), proportion of patients
Costs*, 2007 Can$
Medical cost†
Drug cost only
Total cost
Incremental cost, 2007 Can$
per event averted
per life-year gained
per QALY [95% CI]
Placebo
 95.7% and 98.3% of 1,000 simulations were below a Can$50,000/QALY in the 10-yr and
25-yr horizons, respectively, with almost half (46.3%) of the simulations indicating that
atorvastatin is a dominant treatment strategy.
100%
Increment
0.17
7.40
5.58
0.17
0.26
7.32
5.51
0.19
-0.08
0.07
0.07
-0.02
3,531
2,833
6,364
5,256
186
5,442
-1,725
2,647
922
Probabilistic SA – acceptability curve
Probability of Being Cost-Effective
1BioMedCom
90%
80%
70%
60%
50%
40%
30%
5-Year Results
10-Year Results
25-Year Results
20%
10%
0%
$0
$10
$20
$30
$40
$50
$60
$70
$80
$90
$100
Cost-Effectiveness Threshold, Can$/QALY (Thousands)
Conclusions
11,083
12,327
12,687 [dominant–$66,048]
5-year horizon
QALYs*
Total costs*, 2007 Can$
Incremental cost per QALY, 2007 Can$ [95% CI]
3.26
3.24
3,243
1,855
70,773 [33,981–195,914]
0.02
1,389
25-year horizon
QALYs*
Total costs*, 2007 Can$
Incremental cost per QALY, 2007 Can$ [95% CI]
8.47
8.22
18,988
18,646
1,362 [dominant–$49,432]
0.25
342
 Primary prevention of CV events with atorvastatin 10 mg/day resulted in incremental costeffectiveness ratios well below many other commonly used healthcare interventions15 (10yr: $12,687/QALY; 25-yr: $1,362/QALY).
 Atorvastatin is cost-effective for the primary prevention of major CV events and associated
death among Canadians with type 2 diabetes without established CVD. Univariate and
multuivariate SA indicate that the results are robust to variations in input parameters.
Acknowledgements
CI: confidence interval; LYG: life-year gained; QALY: quality-adjusted life year
*Discounted at 5%; †Includes total cost of hospitalization (including overhead) due to stroke, CHD procedures and CHD medical admissions
This study was funded by Pfizer Canada Inc.
2
One-way deterministic SA – 10-year horizon
 The model was most sensitive to variations in age at baseline ($66,964 to -$1,896/QALY),
followed by HRs for CHD and stroke
 Systolic blood pressure, adherence rate, cholesterol levels, and cost of atorvastatin for
subsequent years also had intermediate impact on incremental ratios.
 The model was robust to variations in other risk factors such as gender, atrial fibrillation,
and smoking status.
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Baseline age 70 yrs / 47 yrs
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HR CHD ±97.5% CI
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HR Stroke ±97.5% CI
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11
SBP ±25%
Adherence rate 100% / 76%
12
TC ±25%
HDL-C ±25%
13
14
Atorvastatin cost for subsequent years (pregeneric) ±97.5% CI
15
Years since diagnosis 14 yrs / 5 yrs
16
Stroke cost +125% / -50%
17
RR Stroke 2nd event ±97.5% CI
18
19
HbA1c 8.9% / 7.1%
Generic activation cycle ±97.5% CI
20
p(die)CHD ±97.5% CI
21
Stroke cost for subsequent years ±97.5% CI
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Incremental cost ($) per QALY gained - 10 years
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