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Examples of Economic Evaluation and Cost-Effectiveness Analysis 151

slightly when compared with clinical dosing. For phenprocoumon, the ICER
was €28,349 per QALY gained; for acenocoumarol, €24,427 per QALY gained
was concluded. Even though, at a willingness-to-pay threshold of €20,000 per
QALY, the pharmacogenetic dosing algorithm was not likely to be cost-effective
compared with the clinical dosing algorithm, the authors stated that availabil-
ity of low-cost genotyping would make it a cost-effective option. For typical
patients with nonvalvural atrial fibrillation, warfarin-related genotyping was
unlikely to be cost-effective, yet might be cost-effective in those patients being at
high hemorrhagic risk. Of particular interest is the study of Jowett et al. (2008)
that focused on the time and traveling costs that patients incur to themselves
and society in order to attend anticoagulation clinics, especially when taking
into account that therapy success requires regular monitoring and, frequently,
dose adjustment. Patients were found to incur considerable costs when visiting
anticoagulation clinics, and these costs varied by country, ranging from €6.9
(France) to €20.5 (Portugal) per visit. No doubt, a broad economic perspective
becomes of fundamental importance when considering the cost-effectiveness
of warfarin (Verhoef et al., 2012).
A few studies have investigated alternatives to warfarin for stroke prophylaxis
in patients with atrial fibrillation, raising the interesting question of whether
these alternatives are cost-effective (Pink et al., 2014). On the basis of the results
from randomized evaluation of long-term anticoagulation therapy (RE-LY)
(Wallentin et al., 2010) and other trials, a decision-analysis model was devel-
oped to compare the cost and quality-adjusted survival of various antithrom-
botic therapies (dabigatran, aspirin, and warfarin) (Shah and Gage, 2011). A
Markov model was run in a hypothetical cohort of 70-year-old patients with
atrial fibrillation, using a cost-effectiveness threshold of $50,000/QALY. Dabi-
gatran 150 mg (twice daily) was found to be cost-effective in patient popula-
tions at high risk of hemorrhage or stroke, unless INR control with warfarin
was excellent. Warfarin was cost-effective in moderate-risk patient populations,
unless INR control was poor. Nevertheless, neither dabigatran nor rivaroxaban
were cost-effective options when relative risks of clinical events served as inputs
to an economic analysis, following a clinical trial simulation of warfarin. Along
the cost-effectiveness frontier, apixaban was the most cost-effective treatment.
Interestingly enough, O’Brien and Gage (2005) compared quality-adjusted
survival and cost among ximelagatran, warfarin, and aspirin for patients with
chronic atrial fibrillation. According to their Semi-Markov decision model
findings and assuming equal effectiveness in stroke prevention and decreased
hemorrhage risk, ximelagatran was not likely to be cost-effective in patients
with atrial fibrillation, unless they had a high risk of intracranial hemorrhage
or a low quality of life with warfarin. On the basis of head-to-head evidence
from randomized controlled trials, the cost-utility of eprosartan versus enala-
pril (primary prevention) and versus nitrendipine (secondary prevention) has