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http://dx.doi.org/10.1016/j.hlc.2015.02.018
Cost-Effectiveness Analysis of
Fondaparinux vs Enoxaparin in Non-ST
Elevation Acute Coronary Syndrome in
Thailand§
Unchalee Permsuwan, PhD a*,
Nathorn Chaiyakunapruk, PharmD, PhD b,c,d,e,
Surakit Nathisuwan, PharmD, BCPS f, Apichard Sukonthasarn, MD g
a
Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
b
School of Pharmacy, Monash University Malaysia, Malaysia
c
Center of Pharmaceutical Outcomes Research (CPOR), Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
d
School of Population Health, University of Queensland, Brisbane, Australia
e
School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA
f
Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
g
Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Received 27 August 2014; received in revised form 2 February 2015; accepted 20 February 2015; online published-ahead-of-print 14 March 2015
Background Non-ST elevation acute coronary syndrome (NSTE-ACS) imposes a significant health and economic burden
on a society. Anticoagulants are recommended as standard therapy by various clinical practice guidelines.
Fondaparinux was introduced and evaluated in a number of large randomised, controlled trials. This study
therefore aimed to determine the cost-effectiveness of fondaparinux versus enoxaparin in the treatment of
NSTE-ACS in Thailand.
Methods A two-part construct model comprising a one-year decision tree and a Markov model was developed to
capture short and long-term costs and outcomes from the perspective of provider and society. Effectiveness
data were derived from OASIS-5 trial while bleeding rates were derived from the Thai Acute Coronary
Syndrome Registry (TACSR). Costs data were based on a Thai database and presented in the year of 2013.
Both costs and outcomes were discounted by 3% annually. A series of sensitivity analyses were performed.
Results The results showed that compared with enoxaparin, fondaparinux was a cost-saving strategy (lower cost
with slightly higher effectiveness). Cost of revascularisation with major bleeding had a greater impact on the
amount of cost saved both from societal and provider perspectives. With a threshold of 160,000 THB
((4,857.3 USD) per QALY in Thailand, fondaparinux was about 99% more cost-effective compared with
enoxaparin.
Conclusion Fondaparinux should be considered as a cost-effective alternative when compared to enoxaparin for
NSTE-ACS based on Thailand’s context, especially in the era of limited healthcare resources.
Keywords Fondaparinux Enoxaparin NSTE-ACS Cost-Effectiveness Thailand
§
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
*Corresponding author at: Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand. Tel.: +66 54944355;
fax: +66 53222741, Email: unchalee.permsuwan@gmail.com
© 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier
Inc. All rights reserved.
Cost-Effectiveness Analysis of Fondaparinux vs Enoxaparin 861
Economic Model from the TACSR which demonstrated the average hospital-
The model in this study was a two-part construct with a isation of 8.6 days for UA patients and 11.8 days for NSTEMI
one-year decision tree, based effectiveness data on the patients [14].
OASIS-5 trial [8], and a Markov model for capturing long- A decision tree began with cohort patients with NSTE-
term costs and benefits (Figure 1). A one-year decision tree ACS. Patients would receive either fondaparinux or
model was used in the first part because the efficacy of enoxaparin. After receiving medication, they underwent
fondaparinux in terms of the reduction of major bleeding revascularisation or continued receiving conservative medi-
occurs rapidly after treatment. The OASIS-5 trial [8] provided cation treatment. The revascularisation included percutane-
the safety outcome at day 9, day 30, and day 180. The result at ous coronary intervention (PCI) or/and coronary artery
day 9 was used in this analysis owing to the clinical evidence bypass graft (CABG). Patients would further have a
Survive
No major bleeding
Die
No revascularization Death
Survive
Major bleeding
Die
Fondaparinux Death
Survive
No major bleeding
Die
Death
Revascularization
Survive
Major bleeding
Die
Death
NSTE-ACS
Survive
No major bleeding
Die
No revascularization Death
Survive
Major bleeding
Die
Death
Enoxaparin
Survive
No major bleeding
Die
Death
Revascularization
Survive
Major bleeding
Die
Death
A A one-year decision tree model
ACS Death
Figure 1 Model structure comparing fondaparinux and enoxaparin in non-ST elevation acute coronary syndrome patients.
Cost-Effectiveness Analysis of Fondaparinux vs Enoxaparin 863
Probabilities
Revascularisation 0.274 0.267-0.282 [15]
Major bleeding after revascularisation 0.058 0.052-0.064 [15]
Major bleeding without revascularisation 0.042 0.038-0.045 [15]
Death with major bleeding 0.279 0.251-0.308 [2]
Death without major bleeding 0.086 0.082-0.090 [2]
Effectiveness of fondaparinux (RR)
On major bleeding 0.52 0.44-0.61 [8]
Costs (THB, year of costing: 2013)
Fondaparinux1 1,320 352-2,112 GSK
Enoxaparin2 2,712 723.2-4,339.2 [18]
Heparin3 128 102.4-153.6 [18]
Revascularisation with major bleeding 386,130 295,536-1,067,795 [19]
Revascularisation with no major bleeding 315,422 305,612-325,232 [19]
No revascularisation with major bleeding 75,377 54,721-96,033 [19]
No revascularisation with no major bleeding 55,826 53,726-57,924 [19]
Direct non-medical cost 1st year 3,382 2,706-4,059 [20]
Direct non-medical cost 2nd year 4,4892 3,913-5,870 [20]
Cost of ACS 1st year 59,405 47,524-71,286 [20]
Cost of ACS 2nd year 13,584 10,867-16,300 [20]
Utility
ACS 0.605 0.509-0.920 [21]
1
Unit cost of fondaparinux sodium prefill syringe 2.5 mg/0.5 ml was 220 THB; Total six day treatment was 1,320 (220*6).
2
Unit cost of enoxaparin sodium 60 mg/0.6 ml was 226 THB; Total six day treatment was 2,712 (226*2*6).
3
Unit cost of heparin 5000 IU/ml was 128 THB.
864 U. Permsuwan et al.
Long-term mortality rate in the Markov model was based [21] from the Health Intervention and Technology Assess-
on the age- and sex-specific mortality rate (ASMR) for the ment Program (HITAP). The utility was 0.605 with a range
Thai population [16]. However, ACS is a serious medical from 0.509 to 0.92.
condition associated with high morbidity and mortality
[14]. The additional mortality risk in ACS patients was quan- Analyses
tified in terms of a relative risk compared to the general Thai The two alternatives were compared on the basis of the
population. This relative risk was based on a secondary increments in costs and effectiveness. The ICER was calcu-
analysis of the Prospective Registry of Acute Ischaemic lated by incremental cost divided by incremental effective-
Syndromes in the UK (PRAIS) study which followed-up ness yielding cost per QALY.
490 ACS patients for four years [17]. Therefore, we calculated
transition probability for ACS to death by multiplying ASMR Sensitivity Analyses
of Thai population by 1.8. A series of sensitivity analyses were performed. One-way
sensitivity analysis was carried out by varying each variable
Healthcare Resources and Costs Parameters while keeping other variables constant. Those varied varia-
Drug costs comprised fondaparinux, enoxaparin, and hepa- bles were costs, relative risks, probabilities, and utility value.
rin. The unit price was 220 THB (6.68 USD)/2.5 mg/0.5 ml Number of days that patients received either fondaparinux
tube, obtained from GSK. The reference prices of enoxaparin or enoxaparin was also varied. This was due to the fact that
and heparin were obtained from Drug and Medical Supply the treatment would last only three days for the treatment of
Information Center (DMSIC), Ministry of Public Health patients with NSTE-ACS as the routine clinical practice in
(http://dmsic.moph.go.th/price.htm) [18]. The standard Thailand. For cost variables, we used 20% for upper and
price of enoxaparin sodium 60 mg/0.6 ml was 226 THB lower range except for costs of major bleeding, for which data
(6.86 USD) and heparin 5,000 IU/ml were 128 THB (3.88 were available [19]. For probability parameters, the range
USD). Based on the OASIS-5 trial [8], the treatment duration would be mean standard error. For other variables, the
lasted for six days. Enoxaparin was administered twice daily study provided the base case value and its range. The results
while fondaparinux was once daily. Therefore, total costs of of one-way sensitivity analysis were displayed as the tornado
enoxaparin and fondaparinux treatment were 2,712 THB diagram.
(82.33 USD) and 1,320 THB (40.07 USD) respectively. Patients In addition, probabilistic sensitivity analysis (PSA) was
receiving fondaparinux who underwent revascularisation undertaken to address uncertainty in the assumptions under-
would receive UFH 100 IU/kg to flush the catheters. lying the model by allowing all of the input parameters’
Costs of major bleeding were derived from the study by values to vary simultaneously over their respective feasible
Saokaew S. [19] which used the database of a University- ranges within the model. All input parameters were assigned
affiliated hospital in Bangkok. This study was a retrospective a probability distribution to reflect their feasible range of
cohort study of hospitalised patients with acute values. A beta distribution was chosen for probability and
coronary syndrome (n=346) comparing cost and length of utility parameters. A log-normal distribution was used for
stay between those with and without bleeding. The cost of RRs’ parameters. A gamma distribution, which ensures pos-
major bleeding for patients who underwent revascularisation itive values, was assigned for all cost parameters. A thousand
and not revascularisation was 386,130 THB (SD=75,870) and iterations were performed. The results were displayed as a
75,377 THB (SD=12,980), respectively. Patients who under- cost-effectiveness acceptability curve which illustrates the
went revascularisation, but did not have major bleeding relationship between the willingness to pay for a unit of
incurred 315,422 THB (SD=49,946), while the medical care outcome and the probability of favouring each strategy [22].
cost of those patients who did not undergo revascularisation
and no major bleeding was 55,826 THB (SD=10,523). The
attributable cost of major bleeding among those with revas-
Results
cularisation was 70,708 THB (SD=25,923) and those without
Base Case Analysis
revascularisation was 19,552 THB (SD=2,458).
Costs of ACS first year, second year, and direct non-medi- We found that fondaparinux treatment was a cost saving
cal costs were obtained from the study by Anukoolsawat P. strategy compared to enoxaparin treatment in both perspec-
[20]. The first year ACS cost accounted for the costs incurred tives. This was the result from less total cost of 962 THB (29.2
after hospitalisation. Since this cost was not actually reported USD) and 1,286 THB (39.0 USD) from the perspectives of society
in the study, we used the difference between the first year and provider respectively. Furthermore, NSTE-ACS patients
who received fondaparinux gained 0.04 more QALY than those
average cost and the first year average admission cost. For the
who received enoxaparin from both perspectives (Table 2).
second year and onward, we assumed the indifferent costs
were due to a paucity of cost data beyond the second year. Sensitivity Analyses
Utility A series of one-way sensitivity analyses from both provider
Due to the lack of direct utility elicitation from the Thai and societal perspectives (Figure 2 and 3) showed that fon-
population, we derived a utility based on the disability daparinux treatment was still a cost-saving strategy com-
weight of ACS patients used in a study by Tamteerano Y. pared with enoxaparin treatment. This was the result from
Cost-Effectiveness Analysis of Fondaparinux vs Enoxaparin 865
Utility (0.509-0.920)
Utility (0.509-0.92)
the less incremental cost with a slightly higher gain in QALY. The result of PSA showed that at a 160,000 THB (4,857.3
Among 22 varied parameters, cost of revascularisation with USD) per QALY threshold in Thailand, fondaparinux treat-
major bleeding had the high impact on cost saving. When it ment was approximately 99% cost-effective compared with
was increased, fondaparinux treatment was more likely to be enoxaparin from both provider and societal perspectives as
a cost-saving strategy. shown in Figures 4 and 5.
1.2
Fondaparinux
1
Probability of being cost-effective
0.8
0.6
0.4
0.2
Enoxaparin
0
1.2
Fondaparinux
1
Probability of being cost-effective
0.8
0.6
0.4
0.2
Enoxaparin
0
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