SciELO - Scientific Electronic Library Online

vol.40 número3Tratamiento hipoglucemiante del paciente diabético en el Servicio de UrgenciasEl consentimiento informado en investigación clínica: ¿entienden los pacientes lo que firman? índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados




Links relacionados

  • En proceso de indezaciónCitado por Google
  • No hay articulos similaresSimilares en SciELO
  • En proceso de indezaciónSimilares en Google


Farmacia Hospitalaria

versión On-line ISSN 2171-8695versión impresa ISSN 1130-6343

Farm Hosp. vol.40 no.3 Toledo may./jun. 2016 



Cost-effectiveness analysis of apixaban compared to low-molecular-weight heparins and vitamin k antagonists for treatment and secondary prevention of venous thromboembolism

Coste-efectividad de apixaban versus heparinas y antagonistas de la vitamina k para el tratamiento y la prevención secundaria del tromboembolismo venoso



Isabel Elías1, Itziar Oyagüez1, Luis Antonio Álvarez-Sala2, Fernando García-Bragado3, Andrés Navarro4, Paloma González5, Fernando de Andrés-Nogales1 and Javier Soto6

1Pharmacoeconomics & Outcomes Research Iberia (PORIB), Pozuelo de Alarcón, Madrid.
2Servicio de Medicina Interna, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, Madrid.
3Servicio de Medicina Interna, Hospital Universitari de Girona Doctor Josep Trueta, Gerona.
4Servicio de Farmacia. Hospital General Universitario de Elche, Alicante.
5Departamento Health Economics, Bristol-Myers Squibb, Madrid.
6Departamento Health Economics, Pfizer, Alcobendas, Madrid. Spain.

This study was funded by Bristol-Myers Squibb and Pfizer.





Objective: Cost-effectiveness analysis of a 6-month treatment of apixaban (10 mg/12h, first 7 days; 5 mg/12h afterwards) for the treatment of the first event of venous thromboembolism (VTE) and prevention of recurrences, versus low-molecular-weight heparins/vitamin K antagonists treatment (LMWH/VKA).
Material and methods: A lifetime Markov model with 13 health states was used for describing the course of the disease. Efficacy and safety data were obtained from AMPLIFY and AMPLIFY-EXT clinical trials; health outcomes were measured as life years gained (LYG) and quality-adjusted life years (QALY). The chosen perspective of this analysis has been the Spanish National Health System (NHS). Drugs, management of VTE and complications costs were obtained from several Spanish data sources (€, 2014). A 3% discount rate was applied to health outcomes and costs. Univariate and probabilistic sensitivity analyses (SA) were performed in order to assess the robustness of the results.
Results: Apixaban was the most effective therapy with 7.182 LYG and 5.865 QALY, versus 7.160 LYG and 5.838 QALYs with LMWH/VKA. Furthermore, apixaban had a lower total cost (€13,374.70 vs €13,738.30). Probabilistic SA confirmed dominance of apixaban (led to better health outcomes with less associated costs) in 89% of the simulations.
Conclusions: Apixaban 5 mg/12h versus LMWH/VKA was an efficient therapeutic strategy for the treatment and prevention of recurrences of VTE from the NHS perspective.

Key words: Anticoagulants; Apixaban; Cost-effectiveness; Deep vein thrombosis; Pulmonary embolism; Venous thromboembolism.


Objetivo: Analizar la relación coste-efectividad de 6 meses de tratamiento con apixaban (10 mg/12 h, 7 primeros días; 5 mg/12 h después) para el primer evento de tromboembolismo venoso (TEV) y prevención de recurrencias, frente a heparinas de bajo peso molecular/antagonistas de vitamina K (HBPM/ AVK).
Material y métodos: Se ha empleado un modelo de Markov con 13 estados de salud que describen la evolución de la enfermedad a lo largo de la vida de los pacientes. Los datos de eficacia y seguridad se han obtenido de los ensayos clínicos AMPLIFY y AMPLIFY-EXT, calculándose los años de vida ganados (AVG) y los años de vida ajustados por calidad (AVAC) de las opciones terapéuticas evaluadas. En este análisis se adoptó la perspectiva del Sistema Nacional de Salud (SNS). El coste de la medicación, de las complicaciones y del manejo del TEV se obtuvo de distintas fuentes españolas (€, 2014). Se aplicó una tasa de descuento anual del 3% a costes y beneficios en salud. Se realizaron análisis de sensibilidad univariante y probabilístico (ASP) para evaluar la robustez de los resultados.
Resultados: Apixaban generó mejores resultados en salud con 7,182 AVG y 5,865 AVAC, frente a 7,160 AVG y 5,838 AVAC para HBPM/AVK, y con menor coste total (13.374,70 € versus 13.738,30 €). El ASP confirmó la dominancia de apixaban (produce mejores resultados con menores costes asociados) en el 89% de las simulaciones.
Apixaban 5 mg/12 h versus HBPM/AVK fue una estrategia eficiente para el SNS en el tratamiento y prevención de recurrencias de TEV.

Palabras clave: Apixaban; Anticoagulante; Coste-efectividad; Embolia pulmonar; Tromboembolismo venoso; Trombosis venosa profunda.


Contribution to scientific literature

What is known about this subject?

Venous Thromboembolism can be considered a relevant condition from the perspective of the healthcare system, because it has been established as the third cause of cardiovascular death at global level. There are currently several treatment options available in the market; the group of new oral anticoagulants are the ones offering the highest number of advantages compared with the rest, because they involve less anticoagulation monitoring in patients and, at the same time, they offer a more favourable safety profile.

What is the contribution of this study to scientific literature?

This cost-effectiveness analysis is the first one conducted in our country in order to assess the costs and health outcomes associated with treatment with apixaban vs. low molecular weight heparins and vitamin K antagonists, for treatment of a first event of venous thromboembolism, and prevention of recurrences. The information and results of this study can be helpful for decision making by the different stakeholders involved.



Venous Thromboembolism (VTE), which includes both Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), represents the third cause of cardiovascular death at a global level1. With approximately 60% of DVT and 40% of PE2,3, the total prevalence of VTE in Spain has been calculated in 0.11%4, with a progressive increase in cases, reaching a diagnosis rate of 154/100,000 inhabitants, including non-hospital diagnosis5.

Patients with VTE have a high risk of recurrences, which is higher during the first two years6, as well as of long-term complications such as Post-Thrombotic Syndrome (PTS) and Chronic Pulmonary Hypertension (CTEPH)7. VTE generates an important use of resources due to these complications and the recurrences which require hospitalization. The studies available have calculated the total cost associated with VTE in Spain in over 75.5 million euros, with an annual 8-9% increase, out of which 79.3% is assigned to hospital healthcare8.

The treatment for VTE is anticoagulation; other treatments such as thrombolysis or inferior vena cava filters are reserved for special situations7. Current treatment guidelines recommend parenteral anticoagulation during the acute phase, with low-molecular-weight heparins (LMWH) during the first 5-10 days, followed by oral anticoagulation during a minimum period of 3 months with Vitamin K antagonists (VKA), such as dabigatran or edoxaban, or otherwise initiating oral treatment with apixaban or rivaroxaban, not requiring any previous parenteral treatment9.

Apixaban is an oral, direct, highly selective Xa factor inhibitor; unlike VKA, it does not need continuous monitoring of the INR value to stay within the therapeutic range and, therefore, it does not require any dose adjustment10.

The efficacy of apixaban for VTE treatment and prevention of recurrences has been supported by the outcomes of a Phase-III clinical trial11, which demonstrated non-inferiority vs. LMWH/VKA.

Additionally to its efficacy assessment, it is interesting to develop other type of studies, with complementary information demonstrating that new therapies are cost-effective vs. other options available.

The objective of the present study was to conduct a cost-effectiveness analysis of apixaban versus LMWH/ VKA for treatment of the first VTE event, and prevention of the recurrences.



The costs and health outcomes of the therapeutic options were estimated through an analytic model, in a cohort of Spanish patients who required anticoagulant treatment for a first VTE event and its recurrences.

Model Structure

The cost-effectiveness analysis was conducted through a Markov Model which simulates the evolution of patients with an acute VTE episode. This technique, widely used for the economic evaluation of medications12,13, represents the natural history of the disease, through the definition of selective health states which show the potential events and situations that a patient can experience. The structure has been based on models accepted by the National Institute for Health and Care Excellence for this condition14,15,16, and was validated by a board of national experts (2 Internal Medicine Specialists and one Hospital Pharmacist). Figure 1 shows the diagram of the model with 13 health states, representative of the clinical events derived of the evolution of the condition or its treatment, and the potential transitions between them. Patients are initially placed in the "first PE or DVT event" health states, and transitions are conducted in 3-month cycles.

Treatment options

The assessed therapies included the combined treatment with LMWH/VKA, represented by enoxaparin and acenocoumarol, vs. apixaban. The dosing schedules considered were enoxaparin 1 mg/kg twice a day and VKA 6 mg/day on the 6 first days, and VKA 3 mg/day until treatment completion. Treatment with apixaban included 10 mg twice a day on the 7 first days, and 5 mg twice a day until completing 6 months, which was the total duration of treatment planned for both arms. The dosing regimens and duration of treatments were those used in the clinical trials of reference. For recurrent events, the treatment initially administered was repeated, except in the case of initial treatment discontinuation before completing the 6 months, where patients were always treated with LMWH/VKA.

Perspective, discount rate, and time horizon

This analysis was conducted from the perspective of the Spanish National Healthcare System (NHS), applying a 3% annual discount rate to costs and health outcomes17. The time horizon of the analysis was lifetime.

Health outcomes

The model considers the risk of developing the following clinical events: recurrent VTE and VTE-related death, major bleeding, clinically relevant non-major bleeding (CRNM), PTS and CTEPH (Table 1). In each cycle, each patient could only present one event.

The risk of developing some event was divided into 2 periods: one initial acute phase of 6 months (sub-divided into 0-3 and 3-6 months), which shows the outcomes observed in the direct comparison study between the alternative options (AMPLIFY study)11 and a subsequent period until reaching the time horizon of the analysis, the entire life of the patient. The risk of suffering an event after permanent treatment discontinuation (by withdrawal or completing treatment) was obtained from literature18,19 and from the extension study arm (AMPLIFY-EXT), where placebo was used as comparator20. The frequency of CTEPH (1,25%)21 and the prevalence of PTS (8.1%)22, which was considered constant, were obtained from scientific literature.

The anticoagulant treatment received had no impact on the nature of fatal haemorrhages, considering that 1346% of all major bleedings were fatal; and 13.97% of those non-fatal were intracranial23. Besides, after 18 months from the embolic event, an incremental risk factor of bleeding was applied of 0.197 per decade of life, because age is an additional risk factor for bleeding24. Regarding discontinuation due to hemorrhagic events, according to data from a secondary analysis of the AMPLIFY study validated by the board of experts, a 2-day discontinuation was considered in CRNM bleeding, and permanent in case of intracranial haemorrhages. For non-intracranial major bleeding 47.27% of patients discontinued treatment during 14 days, while the rest discontinued permanently.

Measurement of health outcomes

The efficacy of alternative treatments determined the development of clinical events and, consequently, the life expectancy of patients. Efficiency was estimated considering total costs and health outcomes in terms of life years gained (LYG), which were subsequently adjusted with the relevant utility values to be expressed as quality-adjusted life years (QALY), accumulated at the end of the simulation. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) between the assessed therapies (apixaban vs. LMWH/VKA) was calculated with the following formulas:

Quality of life

In economic evaluations, the health related quality of life is included through the calculation of QALY, which is derived from the adjustment of survival in LYG, with a utility value which represents the subjective preference of patients for a specific health state.

The model considered different utilities according to the different health states, A baseline utility of 0.82 525 was accepted for patients with VTE without a previous history of complications. The development of intracranial haemorrhage or CTEPH was associated with utilities of 0.33026 and 0.65027, respectively.

Decrements of utilities associated with clinical events and bleedings were taken into account, as well as those associated with the way of administration of the anticoagulant treatment, with a higher impact of the parenteral way in the final utility value (Table 1)26,28,29,30,31,32.

Resources and costs

In line with the analysis perspective, only direct healthcare costs were included (pharmaceutical costs, administration, INR monitoring, and management of VTE and its complications). Non-healthcare or indirect costs were not included. The cost of pharmaceutical treatments was calculated by retail price33, applying the current deductions as relevant34. The board of experts provided the identification and calculation of the necessary resources (medication, number of consultations required, diagnostic tests, etc.) for treatment monitoring and management of the disease and its complications. Unit costs (Table 2) were obtained from scientific literature and a national database of healthcare costs; in those cases where necessary, the variation of the index of consumer prices until the year of this analysis was implemented35,36,37,38. All costs included in the model were expressed in 2014 euros.

Sensitivity analysis

One-way deterministic sensitivity analyses (DSA) as well as probabilistic (PSA) were conducted, in order to assess the impact of certain parameters on the results. In the univariate sensitivity analysis, the following individual modifications were conducted: treatment duration (3 months, 12 months, and lifetime), time horizon (1, 5 and 10 years) and discount rate (0-5%). The PSA involved the simultaneous variation (2,000 Montecarlo simulations) of all parameters considered relevant according to a distribution previously assigned and adjusted to the type of variability presented. The distribution functions applied were: beta (events and utility rates), log-normal (relative costs and risks), gamma (event rates and costs), and Dirichlet (distribution of recurrent VTE according to percentage of death associated with VTE, percentage of were calculated with the standard error and confidence non-fatal PE and DVT). The parameters for distributions intervals for each parameter.



The results obtained for a cohort of 1,000 patients and a lifetime horizon revealed that VTE patients treated with apixaban experienced a lower number of recurrent embolic events, major bleedings and CRNM bleeding than those treated with LMWH/VKA. Table 3 shows the number of events, the LYG and QALY, and the costs associated with the anticoagulant therapy and management of clinical events.

In terms of survival, apixaban provided 7.182 LYG versus 7.160 LYG achieved with LMWH/VKA. Considering the utility values, the average QALY obtained with apixaban was 5.865, versus 5.838 in patients with LMWH /VKA. The total cost was €13,374.70/ patient with apixaban and €13,738.30 with LMWH /VKA. The cost items with the highest differences between the therapeutic options were those associated with anticoagulant treatment (drug cost, administration and monitoring), major bleeding and CRNM bleeding. Treatment with apixaban led to a reduction of €363.6/ patient, compared with LMWH /VKA, with 0.022 LYG and 0.027 QALY gained.

Considering the number of events occurred, LYG and QALY and the costs, it is observed that treatment with apixaban presents higher efficacy in the reduction of recurrent VTE events, bleedings and haemorrhages, with an increase in survival, as well as savings in costs of patient management.

The analysis demonstrated that treatment with apixaban was a dominant treatment option (lower cost and better health outcomes) relative to the use of LMWH / VKA.

Apixaban appeared as dominant treatment vs. LMWH / VKA in all DSA (Table 4), except in the scenario with a lifetime treatment duration, where the total cost of treatment with apixaban was higher than with LMWH / VKA, and could be considered a cost-effective option, because the ICUR (€4,751 / QALY) was lower than the threshold of willingness to pay more frequently used as reference in Spain (€30,000 / additional QALY) 39. Apixaban was a dominant strategy vs. LMWH / VKA in 89% of the PSA simulations (Figure 2).



VTE represents a major public health problem, which affects many millions of people in the world every year. The approximate cost of preventing or treating VTE is 1,300 million dollars in the Western countries; and in Spain, specifically, the cost of hospitalization for PE can reach 20 million euros per year6. Besides, those patients who survive can present chronic episodes that require hospitalization and additional treatments, and many individuals will suffer a reduction in their working ability (less working hours, frequent sick leaves, reduction in productivity, etc.), which increases the clinical and economic impact of VTE.

There is no doubt that standard therapies with VKA are effective, though they entail certain drawbacks inherent to their mechanism of action which can affect the quality of life of patients, such as the potential interactions with drugs and food, and the need for continuous INR monitoring to conduct dose adjustments in order to guarantee good patient control. The existence of poorly-controlled patients is associated with an increase in the risk of complications and in the cost that the NHS must assign for its management, and this shows that there is a real need to develop therapies which not only are more effective, but also offer benefits in terms of safety and quality of life.

The inclusion of new treatment options will frequently represent an increase in pharmaceutical costs, which can be compensated or even lead to savings in the total costs by a lower use of resources for patient management. The new direct-acting oral anticoagulants, such as apixaban, will avoid, for example, the costs associated to INR monitoring required by VKA.

The results of this analysis establish a higher effectiveness of treatment with apixaban due to a reduction in the number of events, which entails improvements in survival (an increase in LYG and QALY), and also represents cost savings of €363.60/patient, with apixaban as a dominant alternative option vs. LMWH /VKA. Dominant treatment options are those that offer higher effectiveness and achieve a reduction in total costs.

Apixaban was dominant in the base case, and in almost all the alternative scenarios. When considering a lifetime treatment, there was an additional incremental cost per and QALY gained of €7,179 and €4,751, and apixaban appear to be a cost-effective option vs. LMWH / VKA based on the cost-effectiveness thresholds presented in scientific literature (€30,000 to €45,000 / QALY)39,40.

Currently, there is no published economic evaluation in our country which compares apixaban versus LMWH /VKA in this indication. This same model has been used for the evaluation of the efficiency of apixaban in other settings such as the United Kingdom41, which established a lifetime cost-effectiveness analysis of treatment for VTE and prevention of recurrences with apixaban vs. LMWH /VKA, and calculated an ICER of £10,820 QALY gained, which was also considered a cost-effective option.

The present analysis has some potential limitations. The theoretical nature of any modelling might not be an accurate representation of daily clinical practice. The validity of the analysis models is determined by the quality of the data they are based upon. In this case, the source used to include efficacy in the model was the pivotal clinical trials with apixaban (AMPLIFY and AMPLIFY EXT)11,20. The use of blinded and randomized clinical trial data can be questionable, due to the rigorous inclusion criteria, and it is recommended to use prospective studies conducted in situation of daily clinical practice whenever available (real world data). The utilities used here were obtained from literature, because the clinical trials conducted with apixaban for this indication did not include the assessment of quality of life through questionnaires that provided utility values that could be used for this economic evaluation. Data from United Kingdom patients were used, because no specific values for the Spanish population were found. These utilities were validated by the board of experts as representative of patients in Spain, confirming that the utility values obtained through the EuroQol-5D questionnaire show no differences among the general population from different European countries42.

Another potential limitation was the exclusion from the model of the risk of recurrent VTE after intracranial haemorrhage and after a first relapse. However, the inclusion of these scenarios would translate into a higher reduction of events for patients on apixaban, due to the lower risk with this alternative option and, therefore, more favourable outcomes for this treatment strategy vs. LMWH / VKA.

The results of this evaluation demonstrate that apixaban is a highly efficient option for the treatment of VTE, and represents a dominant alternative option (better health outcomes with a lower cost) vs. treatment with LMWH / VKA; therefore, it should be the treatment option of choice for patients with VTE.


Conflict of interests

Isabel Elias, Itziar Oyagüez and Fernando de Andrés are conducting their professional activity in PORIB, a consultancy company specialized in the economic evaluation of health technologies, which has received financial support by Bristol-Myers Squibb S.A.U. for preparing this project. Luis Antonio Álvarez-Sala and Fernando García-Bragado have received honoraries from PORIB, for their consultancy services associated with the development of the present project. AN declares not having any conflict of interests. Paloma González is currently employed by Bristol-Myers Squibb S.A.U. Javier Soto is currently employed by Pfizer S.L.U. The authors hereby declare that this economic support has not interfered with the development of this project.



1. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet. 2012;379:1835-46.         [ Links ]

2. Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, et al.; VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98:756-64.         [ Links ]

3. Laporte S, Mismetti P, Décousus H, Uresandi F, Otero R, Lobo JL, et al.; RIETE Investigators. Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation. 2008;117:1711-6.         [ Links ]

4. Liu X, Phatak H, Dillon R, Mitchell S. Epidemiology and mortality of venous thromboembolism across patient populations: a systematic literature review. Value in Health. 2013;16:A1-A298.         [ Links ]

5. Guijarro Merino R, Montes Santiago J, San Román Terán CM. Epidemiología hospitalaria de la enfermedad tromboembólica venosa en España. Med Clin (Barc). 2008;131 Suppl 2:2-9.         [ Links ]

6. Páramo JA, Lecumberri R. Enfermedad tromboembólica venosa: una llamada urgente a la acción. Med Clin (Barc). 2009;133:547-51.         [ Links ]

7. Wells P, Anderson D. The diagnosis and treatment of venous thromboembolism. Hematology Am Soc Hematol Educ Program. 2013;2013:457-63.         [ Links ]

8. Grupo Multidisciplinario para el Estudio de la Enfermedad Tromboembólica en España. Estudio sobre la enfermedad tromboembólica venosa en España. Sociedad Española de Medicina Interna: Madrid; 2006. Disponible en: bolica/publicaciones/estudio-etv.pdf (Acceso 20/03/2014).         [ Links ]

9. Konstantinides S, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, et al. 2014 ESC Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism. Rev Esp Cardiol. 2015;68:64.         [ Links ]

10. Agencia Española de Medicamentos y Productos Sanitarios. Ficha técnica de Eliquis®. Disponible en: ibrary/EPAR_-_Product_Information/human/002148/WC500107728.pdf (Acceso 30/7/2014).         [ Links ]

11. Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al.; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369:799-808.         [ Links ]

12. Caro JJ, Briggs AH, Siebert U, Kuntz KM, Force I-SMGRPT. Modeling good research practices - overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-1. Value Health. 2012;15:796-803.         [ Links ]

13. Siebert U, Alagoz O, Bayoumi AM, Jahn B, Owens DK, Cohen DJ, et al.; ISPOR-SMDM Modeling Good Research Practices Task Force. State-transition modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-3. Value Health. 2012;15:812-20.         [ Links ]

14. National Institute for Health and Care Excellence. NICE technology appraisal guidance 287. Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism. Junio 2013. Disponible en:         [ Links ]

15. National Institute for Health and Care Excellence. NICE technology appraisal guidance 261. Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism. Julio 2012. Disponible en:         [ Links ]

16. National Institute for Health and Care Excellence. NICE technology appraisal guidance 327. Dabigatran etexilate for thetreatment and secondary preventionof deep vein thrombosis and/orpulmonary embolism. Diciembre 2014.         [ Links ]

17. López Bastida J, Oliva J, Antoñanzas F, García-Altés A, Gisbert R, Mar J, et al. Propuesta de guía para la evaluación económica aplicada a las tecnologías sanitarias. Gac Sanit. 2010;24:154-70.         [ Links ]

18. Poli D, Grifoni E, Antonucci E, Arcangeli C, Prisco D, Abbate R, et al. Incidence of recurrent venous thromboembolism and of chronic thromboembolic pulmonary hypertension in patients after a first episode of pulmonary embolism. J Thromb Thrombolysis. 2010;30:294-9.         [ Links ]

19. Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica. 2007;92:199-205.         [ Links ]

20. Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368:699-708.         [ Links ]

21. Miniati M, Monti S, Bottai M, Scoscia E, Bauleo C, Tonelli L, et al. Survival and restoration of pulmonary perfusion in a long-term follow-up of patients after acute pulmonary embolism. Medicine (Baltimore). 2006;85:253-62.         [ Links ]

22. Prandoni P, Villalta S, Bagatella P, Rossi L, Marchiori A, Piccioli A, et al. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients. Haematologica. 1997;82:423-8.         [ Links ]

23. Linkins L, O'Donnell M, Julian JA, Kearon C. Intracranial and fatal bleeding according to indication for long-term oral anticoagulant therapy. Journal of thrombosis and haemostasis. JTH. 2010;8:2201-7.         [ Links ]

24. Ariesen MJ, Claus SP, Rinkel GJ, Algra A. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke. 2003;34:2060-5.         [ Links ]

25. Kind P, Dolan P, Gudex C, Williams A. Variations in population health status: results from a United Kingdom national questionnaire survey. BMJ. 1998;316:736-41.         [ Links ]

26. Locadia M, Bossuyt PM, Stalmeier PF, Sprangers MA, van Dongen CJ, Middeldorp S, et al. Treatment of venous thromboembolism with vitamin K antagonists: patients' health state valuations and treatment preferences. Thromb Haemost. 2004;92:1336-41.         [ Links ]

27. Ghofrani HA, D'Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, et al.; CHEST-1 Study Group. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013;369:319-29.         [ Links ]

28. National Institute of Health and Care Excellence (NICE); Venous thromboembolism: reducing the risk; January 2010; NICE CG92. Disponible en: e-venous-thromboembolism-reducing-the-risk-pdf.         [ Links ]

29. Hogg K, Kimpton M, Carrier M, Coyle D, Forgie M, Wells P. Estimating quality of life in acute venous thrombosis. JAMA Intern Med. 2013;173:1067-72.         [ Links ]

30. Sullivan PW, Slejko JF, Sculpher MJ, Ghushchyan V. Catalogue of EQ-5D scores for the United Kingdom. Med Decis Making. 2011;31:800-80.         [ Links ]

31. Lenert LA, Soetikno RM. Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis. J Am Med Inform Assoc. 1997;4:49-56.         [ Links ]

32. Gage BF, Cardinalli AB, Owens DK. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med. 1996;156:1829-36.         [ Links ]

33. Base de Datos de Medicamentos del Consejo General de Colegios Farmacéuticos. Disponible en: (Acceso 31/07/2014).         [ Links ]

34. Ministerio de Sanidad, Servicios Sociales e Igualdad. Listado de medicamentos afectados por las deducciones del Real Decreto-Ley 8/2010- Julio 2014. Disponible en: (Acceso 31/07/2014).         [ Links ]

35. Oblikue Consulting. Base de datos de costes sanitarios. eSalud - Información económica del sector sanitario. Disponible en: (Acceso 01/08/2014).         [ Links ]

36. Barón Esquivias G, Escolar Albaladejo G, Zamorano JL, Betegón Nicolás L, Canal Fontcuberta C, de Salas-Cansado M, et al. Análisis coste-efectividad de apixabán frente a acenocumarol en la prevención del ictus en pacientes con fibrilación auricular no valvular en España. Rev Esp Cardiol. 2015;68:680-90.         [ Links ]

37. Ministerio de Sanidad, Servicios Sociales e Igualdad. Instituto de Información Sanitaria. (2013). Registro de altas. CIE9 MC - CMBD 2011. Disponible en: /DefaultPublico.aspx (Acceso 20/03/2015).         [ Links ]

38. Monreal M, González-Rojas N, Vieta A, Wolowacz SE. Análisis económico de dabigatrán etexilato en prevención primaria del tromboembolismo venoso tras artroplastia total de cadera o rodilla. Pharmacoecon Span Res Art. 2009,6:105-162.         [ Links ]

39. Sacristán JA, Oliva J, Del Llano J, Prieto L, Pinto JL. ¿Qué es una tecnología sanitaria eficiente en España? Gac Sanit. 2002;16:334-43.         [ Links ]

40. De Cock E, Miravitlles M, González-Juanatey JR, Azanza-Perea JR. Valor umbral del coste por año de vida ganado para recomendar la adopción de tecnologías sanitarias en España: evidencias procedentes de una revisión de la literatura. Pharmacoeconomics Spanish Research Articles. 2007;4:97-107.         [ Links ]

41. Lanitis T, Hamilton M, Rublee DA, Leipold R, Quon P, Browne C, et al. Cost-effectiveness of apixaban compared to other anticoagulants for lifetime treatment and prevention of recurrent venous thromboembolism. Value Health. 2014;17:A488.         [ Links ]

42. Greiner W, Weijnen T, Nieuwenhuizen M, Oppe S, Badia X, Busschbach J, et al. A single European currency for EQ-5D health states. Results from a six-country study. Eur J Health Econ. 2003;4(3):222-31.         [ Links ]



Dirección para correspondencia:
Correo electrónico:
(Itziar Oyagüez).

Recibido el 25 de enero de 2016;
aceptado el 12 de marzo de 2016.

Creative Commons License Todo el contenido de esta revista, excepto dónde está identificado, está bajo una Licencia Creative Commons