Benefit, risk and cost of new oral anticoagulants and warfarin in atrial fibrillation; A multicriteria decision analysis
May
Benefit, risk and cost of new oral anticoagulants and warfarin in atrial fibrillation; A multicriteria decision analysis
Jose Mendoza-Sanchez 0 1
Federico Silva 0 1
Lady Rangel 1
Linda Jaramillo 0 1
Leidy Mendoza 0 1
Jenny Garzon 0 1
Andrea Quiroga 0 1
0 Grupo de Ciencias Neurovasculares, Instituto Neurol oÂgico, Hospital Internacional, Fundaci oÂn Cardiovascular de Colombia , Floridablanca, Santander , Colombia , 2 Universidad Industrial de Santander , Bucaramanga, Santander , Colombia
1 Editor: Pasquale Abete, Universita degli Studi di Napoli Federico II , ITALY
Warfarin and new oral anticoagulants are effective in reducing stroke in atrial fibrillation; however, the benefits and risks rates in clinical trials show heterogeneity for each anticoagulant, and is unknown the cost influence on a model considering most of the treatment consequences. We designed a benefit-risk and cost assessment of oral anticoagulants. We followed the roadmap proposed by IMI-PROTECT and the considerations of emerged good practice to perform Multi-Criteria Decision Analysis (MCDA). The roadmap defines the following steps: (1) planning, (2) evidence gathering and data preparation, (3) analyses, (4) explorations, and (5) conclusions. We defined two reference points (0±100) to allocate numerical values for scores and weights, and used an analogue numeric scale to assess physicians' preferences. As benefits of the anticoagulant therapy, we included reductions in stroke and all-cause mortality; intracranial haemorrhage, gastrointestinal haemorrhage, minor bleeding and myocardial infarction were considered risks. We also made an estimation of the annual drug cost per person.
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Data Availability Statement: All relevant data are
within the paper.
Funding: The authors received no specific funding
for this work.
Competing interests: The authors have declared
that no competing interests exist.
Design
Main results
Conclusions
The scores were: Apixaban 33, Dabigatra n 25, warfarin 18 and Rivaroxaban 14 this score
reveals the most preferred up to the less preferred option, considering the benefit-risk ratio
and drug costs altogether. The relative model weights were: 51.1% for risks, 40.4% for
benefits and 8.5% for cost. The sensitivity analysis confirms the model robustness.
From this analysis, apixaban should be considered as the preferred anticoagulant option
-due to a better benefit-risk balance and a minor cost influence- followed by dabigatran,
warfarin and rivaroxaban.
Introduction
Warfarin and new oral anticoagulants are effective in reducing stroke risk in atrial fibrillation
(AF). However, oral anticoagulation drugs also have risks as: major bleeding (2% - 5% annual),
fatal bleeding (0.5% - 1%) and intracranial haemorrhage (0.2% - 0.4% annual);Other sources
of bleeding such as gastrointestinal haemorrhage, have been described with warfarin use [
1
].
New Oral Anticoagulants (NOACs) -apixaban, dabigatran and rivaroxaban-have showed
heterogeneous results: Apixaban reduces risk of stroke without increasing risk of major bleeding
or intracranial haemorrhage; dabigatran 150mg reduces risk of stroke with similar bleeding
risk, but slightly increases gastrointestinal bleeding and myocardial infarction risk;
rivaroxaban may be as effective as warfarin in preventing stroke or systemic embolism[
2
] [
3
] [
4
] [
5
]. In
this context, the election of the most suitable anticoagulant becomes a task.
Doctors elect drugs based not only on their benefits and security profile but also on their
costs, especially when patients have to pay because it impacts on drug outcomes [
6
] [
7
]. Cost
seems to be the most important factor decision to prescribe dabigatran (cost 25%, renal
function 21% and CHADS2 score 18%) and the second more often considered in patients with
warfarin (unstable international ratio 37% and cost 19%) [
8
]. Thus, drugs evaluations with a
holistic view (benefit-risk-cost) are useful to elect a drug. For assessments on which multiple
points are considered, the Multicriteria Decision Analysis (MCDA) allows performing these
evaluations. It provides a carefully balancing of benefits and harms as a numeric value;
furthermore, it is widely used by pharmaceutical companies, regulators and academics to perform
benefits-risk assessments (BRA) [
9
] [
10
].
Two MCDA for oral anticoagulants have been published, both show dabigatran 150mg as the
preferred option [
11
] [
12
], one of them includes costs as a criterion, and both differ on criteria
election as well as scores, criteria weighted and others. The cost inclusion in this model was with
the aim of evaluate events cost from a payer perspective. But doctors decisions tend to integrate
multiple information with different relevance, in order to choose the mostÐsuitable option. We
designed a MCDA for new oral anticoagulants and warfarin integrating clinical events (benefits
and risks) with drug cost to find the best oral anticoagulant from doc (...truncated)