Benefit, risk and cost of new oral anticoagulants and warfarin in atrial fibrillation; A multicriteria decision analysis

PLOS ONE, Nov 2019

Introduction 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. Design 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. Main results The scores were: Apixaban 33, Dabigatrán 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. Conclusions 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.

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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. - 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)


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Jose Mendoza-Sanchez, Federico Silva, Lady Rangel, Linda Jaramillo, Leidy Mendoza, Jenny Garzon, Andrea Quiroga. Benefit, risk and cost of new oral anticoagulants and warfarin in atrial fibrillation; A multicriteria decision analysis, PLOS ONE, 2018, Volume 13, Issue 5, DOI: 10.1371/journal.pone.0196361