Clinical Practice Guideline for the secondary prevention of stroke. Update
Resumida HTML
Question
Recommendations
-
After analysing the evidence available on apixaban compared to warfarin (given the lack of other comparators in the literature meeting the proposed criteria for inclusion and prioritisation), the following recommendation was made:
In adult patients with indications for secondary prevention of stroke and nonvalvular atrial fibrillation, we suggest using apixaban rather than warfarin.
Rationale
Below, we outline the rationale for one of the recommendations, highlighting the judgements of the GDG concerning the key criteria that justify the final recommendation.
The GDG considered reduction in stroke recurrence (a desirable effect) and severe bleeding (an undesirable effect) to be the most important outcomes for assessing potential benefits. Regarding stroke recurrence, it considered the reduction observed in patients treated with apixaban compared to those treated with warfarin to be significant (16 fewer cases of stroke per 1000; a relative reduction of 29%). Regarding severe bleeding, it was considered that the risk of bleeding was lower in patients treated with apixaban than those treated with warfarin (16 cases of bleeding per 1000, a relative reduction of 27%). These considerations justified a recommendation in favour of the use of apixaban.
This recommendation was additionally supported by evidence in the literature of the importance patients place on reducing stroke recurrence (rating it even higher than avoiding death). Further, health professionals considered that apixaban was easier to use given that it does not require regular monitoring and shows little interaction with foods or other drugs.
Similarly, the GDG indicated that improvements in patient quality of life observed in clinical experience with apixaban supported this weak recommendation in favour.
Complete clinical question
For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/guia-de-practica-clinica-sobre-prevencion-secundaria-de-ictus-actualizacion/#question-1
References
4. MacLean S, Mulla S, Akl EA, Jankowski M, Vandvik PO, Ebrahim S, et al. Patient values and preferences in decision making for antithrombotic therapy: a systematic review: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest [Online]. 2012 [accessed June 2021];141(2 Suppl):e1S-e23S. URL: https://doi.org/10.1378/chest.11-2290.
5. Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, et al. Antithrombotic therapy for atrial fibrillation: CHEST Guideline and Expert Panel Report. Chest [Online]. 2018 [accessed June 2021];154(5):1121-201. URL: https://doi.org/10.1016/j.chest.2018.07.040.
19. GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University; 2020 [accessed June 2021]. URL: https://gradepro.org.
20. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J [Online]. 2012 [accessed May 2021];22(21):2719-49. URL: https://doi.org/10.1093/eurheartj/ehs253.
21. Hart RG, Halperin JL. Atrial fibrillation and stroke: concepts and controversies. Stroke [Online]. 2001 Mar [accessed June 2021];32(3):803-8. URL: https://doi.org/10.1161/01.STR.32.3.803.
22. Koton S, Tsabari R, Molshazki N, Kushnir M, Shaien R, Eilam A, et al. Burden and outcome of prevalent ischemic brain disease in a national acute stroke registry. Stroke [Online]. 2013 Dec [accessed June 2021];44(12):3293-7. https://doi.org/10.1161/strokeaha.113.002174.
23. Esenwa C, Gutierrez J. Secondary stroke prevention: challenges and solutions. Vasc Health Risk Manag [Online]. 2015 [accessed May 2021];11:437-50. URL: https://doi.org/10.2147/vhrm.s63791.
24. van Brabandt H, San Miguel L, Fairon N, Vaes B, Henrard S, Boshnakova A, et al. Anticoagulants in non-valvular atrial fibrillation – Synthesis [Online]. Brussels: Belgian Health Care Knowledge Centre (KCE). 2016 [accessed June 2021]. (KCE Reports. Health Technology Assessment HTA; 279Cs). URL: https://kce.fgov.be/sites/default/files/page_documents/KCE_279C_Novel_Anticoagulants_Synthese.pdf.
25. Pinyol C, Cepeda JM, Roldan I, Roldan V, Jiménez S, González P, et al. A systematic literature review on the cost-effectiveness of apixaban for stroke prevention in non¬valvular atrial fibrillation. Cardiol Ther [Online]. 2016 [accessed June 2021];5:171-86. URL: https://doi.org/10.1007/s40119-016-0066-2.
26. Barón-Esquivias G, Escolar Albadalejo G, Zamorano JL, Betegón Nicolas L, Canal Fontcuberta C, Salas-Casado 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 [online]. 2015 [accessed May 2021];68(8):680-90. URL: https://doi.org/10.1016/j.rec.2014.08.010.
27. Escolar-Albadalejo G, Barón-Esquivias G, Zamorano JL, Betegón-Nicolás L, Canal Fontcuberta C, Salas-Cansado M, et al. Análisis coste-utilidad de apixabán frente al ácido acetilsalicílico en la prevención del ictus en pacientes con fibrilación auricular no valvular en España. Aten Primaria [Online]. 2016 [accessed May 2021];48(6):394-405. URL: https://doi.org/10.1016/j.aprim.2015.04.012.
28. Informe de Posicionamiento Terapéutico UT_ACOD/V5/21112016. Criterios y recomendaciones generales para el uso de los anticoagulantes orales directos (ACOD) en la prevención del ictus y la embolia sistémica en pacientes con fibrilación auricular no valvular [Online]. Madrid: Ministerio de Sanidad, Servicios Sociales e Igualdad. Agencia Española de Medicamentos y Productos Sanitarios; 21 Nov 2016 [accessed June 2021]. URL: https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/criterios-anticoagulantes-orales.pdf.
29. Paciaroni M, Agnelli G, Falocci N, Tsivgoulis G, Vadikolias K, Liantinioti C, et al. Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study. J Am Heart Assoc [Online]. 2017 Nov [accessed June 2021];6(12):e007034. URL: https://doi.org/10.1161/jaha.117.007034.
30. Easton JD, Lopes RD, Bahit MC, Wojdyla DM, Granger CB, Wallentin L, et al. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol [Online]. 2012 Jun [accessed May 2021];11(6):503-11. URL: https://doi.org/10.1016/s1474-4422(12)70092-3. Erratum in: Lancet Neurol. 2012 Dec;11(12):1021.
31. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med [Online]. 2011 Sep [accessed May 2021];365(11):981-92. URL: https://doi.org/10.1056/nejmoa1107039.
32. Åsberg S, Eriksson M, Henriksson KM, Terént A. Reduced risk of death with warfarin – results of an observational nationwide study of 20 442 patients with atrial fibrillation and ischaemic stroke. Int J Stroke [online]. 2013 [accessed May 2021];8(8):689-95. URL: https://doi.org/10.1111%2Fj.1747-4949.2012.00855.x.
33. Kodani E, Atarashi H, Inoue H, Okumura K, Yamashita T, Origasa H. Secondary prevention of stroke with warfarin in patients with nonvalvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry. J Stroke Cerebrovasc Dis [Online]. 2016 [accessed June 2021];25(3):585-99. URL: https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.11.020.
34. Xian Y, Wu J, O’Brien EC, Fonarow GC, Olson DWM, Schwamm L, et al. Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study. BMJ [Online]. 2015 [accessed June 2021];351:h3786. URL: https://doi.org/10.1136/bmj.h3786.
35. Luger S, Hohmann C, Niemann D, Kraft P, Gunreben I, Neumann-Haefelin T, et al. Adherence to oral anticoagulant therapy in secondary stroke prevention – impact of the novel oral anticoagulants. Patient Prefer Adherence [Online]. 2015 [accessed June 2021];9:1695-705. URL: https://doi.org/10.2147/ppa.s88994.
36. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke [Online]. 2018 Mar [accessed June 2021];49(3):e46-e110. URL: https://doi.org/10.1161/str.0000000000000158. Erratum in: Stroke. 2018 Mar;49(3):e138. Erratum in: Stroke. 2018 Apr 18; 49(6):e233-4.
37. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J [Online]. 2016 [accessed June 2021];37(38):2893-962. URL: https://doi.org/10.1093/eurheartj/ehw210.
38. Wein T, Lindsay MP, Côté R, Foley N, Berlingieri J, Bhogal S et al. Canadian stroke best practice recommendations: Secondary prevention of stroke, sixth edition practice guidelines, update 2017. Int J Stroke [Online]. 2018 [accessed June 2021];13(4):420-43. URL: https://doi.org/10.1177/1747493017743062.
39. Vanacker P, Standaert D, Libbrecht N, Vansteenkiste I, Bernard D, Yperzeele L, et al. An individualized coaching program for patients with acute ischemic stroke: Feasibility study. Clin Neurol Neurosurg [Online]. 2017 [accessed June 2021];154:89-93. URL: https://doi.org/10.1016/j.clineuro.2017.01.017.
Question
Recommendations
After analysing the evidence available on 110 mg dabigatran compared to warfarin (given the lack of other comparators in the literature meeting the proposed criteria for inclusion and prioritisation), the following recommendation was made:
In adult patients with an indication for the secondary prevention of stroke and non-valvular atrial fibrillation, we suggest using dabigatran 110 mg twice daily rather than warfarin.
Rationale
Below, we outline the rationale for one of the recommendations, highlighting the judgements of the GDG concerning the key criteria that justify the final recommendation.
The GDG indicated that the all-cause and vascular mortality outcomes may differ significantly in favour of the intervention. It considered that the benefit of the intervention (25 fewer all-cause deaths per 1000 treated with 110 mg dabigatran, a relative reduction of 28%) was relevant and conclusive in favour of the intervention, as the confidence interval (CI) did not include the null value.
The benefits in terms of safety were favourable for dabigatran 110 mg, with a lower risk of bleeding with this treatment compared to warfarin (27 fewer cases of bleeding per 1000, a relative reduction of 33%), and the CI did not include the null value; however, regarding myocardial infarction, dabigatran 110 mg had an undesirable effect, with three more events in the intervention group than the comparator (warfarin), although the results were not conclusive given that the CI did include the null value.
The GDG considered that the risk-benefit balance was favourable for dabigatran 110 g compared to warfarin.
The magnitude of the desirable and undesirable effects in relation to all-cause mortality, vascular mortality and severe bleeding may be considered moderate (favourable for the intervention); however, evidence on the outcomes of acute myocardial infarction and stroke recurrence was inconclusive.
The GDG indicated that the weak recommendation in favour was also supported by improvements in patient clinical condition and quality of life observed in clinical experience with dabigatran 110 mg, as well as the greater ease of use, with no requirement for monitoring and only a weak interaction with foods and other drugs.
Complete clinical question
For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/guia-de-practica-clinica-sobre-prevencion-secundaria-de-ictus-actualizacion/#question-1
References
4. MacLean S, Mulla S, Akl EA, Jankowski M, Vandvik PO, Ebrahim S, et al. Patient values and preferences in decision making for antithrombotic therapy: a systematic review: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest [Online]. 2012 [accessed June 2021];141(2 Suppl):e1S-e23S. URL: https://doi.org/10.1378/chest.11-2290.
5. Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, et al. Antithrombotic therapy for atrial fibrillation: CHEST Guideline and Expert Panel Report. Chest [Online]. 2018 [accessed June 2021];154(5):1121-201. URL: https://doi.org/10.1016/j.chest.2018.07.040.
29. Paciaroni M, Agnelli G, Falocci N, Tsivgoulis G, Vadikolias K, Liantinioti C, et al. Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study. J Am Heart Assoc [Online]. 2017 Nov [accessed June 2021];6(12):e007034. URL: https://doi.org/10.1161/jaha.117.007034.
33. Kodani E, Atarashi H, Inoue H, Okumura K, Yamashita T, Origasa H. Secondary prevention of stroke with warfarin in patients with nonvalvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry. J Stroke Cerebrovasc Dis [Online]. 2016 [accessed June 2021];25(3):585-99. URL: https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.11.020.
35. Luger S, Hohmann C, Niemann D, Kraft P, Gunreben I, Neumann-Haefelin T, et al. Adherence to oral anticoagulant therapy in secondary stroke prevention – impact of the novel oral anticoagulants. Patient Prefer Adherence [Online]. 2015 [accessed June 2021];9:1695-705. URL: https://doi.org/10.2147/ppa.s88994.
40. Bonet Pla A, Gosalbes Sóler V, Ridao-López M, Navarro Pérez J, Navarro Cubells B, Peiró S. Dabigatrán versus acenocumarol para la prevención del ictus en la fibrilación atrial: análisis de impacto presupuestario en un departamento sanitario. Rev Esp Salud Pública [Online]. 2013 Jul-Aug [accessed May 2021];87(4):331-42. URL: https://doi.org/10.4321/s1135-57272013000400004
41. González-Juanatey JR, Álvarez-Sabin J, Lobos JM, Martínez-Rubio A, Reverter JC, Oyagüez I, et al. Análisis coste-efectividad de dabigatrán para la prevención de ictus y embolia sistémica en fibrilación auricular no valvular en España. Rev Esp Cardiol [Online]. 2012 [accessed May 2021];65(10):901-10. URL: https://doi.org/10.1016/j.recesp.2012.06.006
42. Carles M, Brosa M, Souto JC, Garcia-Alamino JM, Guyatt G, Alonso-Coello P. Cost-effectiveness analysis of dabigatran and anticoagulation monitoring strategies of vitamin K antagonist. BMC Health Serv Res [Online]. 2015 Jul [accessed May 2021];15:289. URL: https://doi.org/10.1186/s12913-015-0934-9
43. Monreal-Bosch M, Soulard S, Crespo C, Brand S, Kansal A. Comparación del coste-utilidad de los anticoagulantes orales de acción directa en la prevención de ictus en la fibrilación auricular no valvular en España. Rev Neurol. 2017;64(6):247-56.
44. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med [Online]. 2009 [accessed May 2021];361(12):1139:51. URL: https://doi.org/10.1056/nejmoa0905561
45. Diener HC, Connolly SJ, Ezekowitz MD, Wallentin L, Reilly PA, Yang S, et al. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol [Online]. 2010 Dec [accessed May 2021];9(12):1157-63. URL: https://doi.org/10.1016/s1474-4422(10)70274-x. Erratum in: Lancet Neurol. 2011 Jan;10(1):27.
Question
Recommendations
After analysing the evidence available on dabigatran 150 mg compared to warfarin (given the lack of other comparators in the literature meeting the proposed criteria for inclusion and prioritisation) the following recommendation was made.
In adult patients with an indication for secondary prevention of stroke and non-vascular atrial fibrillation, we suggest using dabigatran 150 mg twice daily rather than warfarin.
Rationale
Below, we outline the rationale for one of the recommendations, highlighting the judgements of the GDG concerning the key criteria that justify the final recommendation.
The GDG stated that the were no significant differences in favour of or against the intervention for any of the outcomes. Nonetheless, the GDG indicated that a weak recommendation in favour was supported by improvements in patients’ clinical condition and quality of life observed in clinical experience with dabigatran 150 mg, as well as the greater ease of use, with no requirement for monitoring and only a weak interaction with foods and other drugs.
The weak recommendation in favour of the intervention is the result of weighing the risk-benefit balance in favour of or against dabigatran 150 mg, very low confidence in the evidence and uncertainty concerning whether the reported effect of the intervention might differ from the true effect. The magnitude of the desirable and undesirable effects may be considered small for all the outcomes except for the reduction in acute myocardial infarction, which could be considered moderate in favour of the comparator (warfarin).
Complete clinical question
For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/guia-de-practica-clinica-sobre-prevencion-secundaria-de-ictus-actualizacion/#question-1
References
4. MacLean S, Mulla S, Akl EA, Jankowski M, Vandvik PO, Ebrahim S, et al. Patient values and preferences in decision making for antithrombotic therapy: a systematic review: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest [Online]. 2012 [accessed June 2021];141(2 Suppl):e1S-e23S. URL: https://doi.org/10.1378/chest.11-2290.
5. Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, et al. Antithrombotic therapy for atrial fibrillation: CHEST Guideline and Expert Panel Report. Chest [Online]. 2018 [accessed June 2021];154(5):1121-201. URL: https://doi.org/10.1016/j.chest.2018.07.040.
29. Paciaroni M, Agnelli G, Falocci N, Tsivgoulis G, Vadikolias K, Liantinioti C, et al. Early Recurrence and Major Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation Treated with Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study. J Am Heart Assoc [Online]. 2017 Nov [accessed June 2021];6(12):e007034. URL: https://doi.org/10.1161/jaha.117.007034.
33. Kodani E, Atarashi H, Inoue H, Okumura K, Yamashita T, Origasa H. Secondary prevention of stroke with warfarin in patients with nonvalvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry. J Stroke Cerebrovasc Dis [Online]. 2016 [accessed June 2021];25(3):585-99. URL: https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.11.020.
35. Luger S, Hohmann C, Niemann D, Kraft P, Gunreben I, Neumann-Haefelin T, et al. Adherence to oral anticoagulant therapy in secondary stroke prevention – impact of the novel oral anticoagulants. Patient Prefer Adherence [Online]. 2015 [accessed June 2021];9:1695-705. URL: https://doi.org/10.2147/ppa.s88994.
40. Bonet Pla A, Gosalbes Sóler V, Ridao-López M, Navarro Pérez J, Navarro Cubells B, Peiró S. Dabigatrán versus acenocumarol para la prevención del ictus en la fibrilación atrial: análisis de impacto presupuestario en un departamento sanitario. Rev Esp Salud Pública [Online]. 2013 Jul-Aug [accessed May 2021];87(4):331-42. URL: https://doi.org/10.4321/s1135-57272013000400004
41. González-Juanatey JR, Álvarez-Sabin J, Lobos JM, Martínez-Rubio A, Reverter JC, Oyagüez I, et al. Análisis coste-efectividad de dabigatrán para la prevención de ictus y embolia sistémica en fibrilación auricular no valvular en España. Rev Esp Cardiol [Online]. 2012 [accessed May 2021];65(10):901-10. URL: https://doi.org/10.1016/j.recesp.2012.06.006
44. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med [Online]. 2009 [accessed May 2021];361(12):1139:51. URL: https://doi.org/10.1056/nejmoa0905561
45. Diener HC, Connolly SJ, Ezekowitz MD, Wallentin L, Reilly PA, Yang S, et al. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol [Online]. 2010 Dec [accessed May 2021];9(12):1157-63. URL: https://doi.org/10.1016/s1474-4422(10)70274-x. Erratum in: Lancet Neurol. 2011 Jan;10(1):27.
Question
Recommendations
After analysing the evidence available on edoxaban compared to warfarin (given the lack of other comparators in the literature meeting the proposed criteria for inclusion and prioritisation), the following recommendation was made:
In adult patients with an indication for the secondary prevention of stroke and non-valvular atrial fibrillation, we suggest using edoxaban rather than warfarin.
Rationale
Below, we outline the rationale for one of the recommendations, highlighting the judgements of the GDG concerning the key criteria that justify the final recommendation.
The GDG considered that the cardiovascular mortality outcome (desirable effect: a reduction) provided the most important benefits. It considered that the benefit of the intervention (20 fewer deaths per 1000, a relative reduction of 21%) was significant; the benefit in terms of safety was favourable for edoxaban, with a lower risk of bleeding with this treatment than with warfarin (13 fewer cases of bleeding per 1000, a relative reduction of 16%). Nonetheless, the CI included the null value, and hence, the GDG had little confidence in the evidence, as the effect of the intervention obtained in the study might differ from the true effect.
In this comparison, results in terms of stroke recurrence supported the intervention (9 fewer cases of stroke per 1000), although the CI did include the null value. The recommendation was also influenced by some studies having described patients preferring a reduction in stroke recurrence over improvements in other outcomes (even death).
The magnitude of the desirable and undesirable effects may be considered small.
The GDG had very low confidence in the estimate of the effect, especially because of the risk of bias and imprecision in the results, and hence, the risk-benefit balance was not clear and showed only weak support for benefits.
Nonetheless, the GDG indicated that a weak recommendation in favour was supported by improvements in patients’ clinical condition and quality of life observed in clinical experience with edoxaban.
The conditional recommendation in favour of the intervention was reached after assessing the risk-benefit balance of using edoxaban rather than warfarin for the secondary prevention of stroke. In this assessment, it was considered that the balance would be positive (beneficial), although with a very low level of confidence in the available evidence, the expected effect possibly differing from the true effect (in the real world).
For the aforementioned reasons, the recommendation is weakly in favour of the intervention (edoxaban) over the comparator (warfarin).
Complete clinical question
For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/guia-de-practica-clinica-sobre-prevencion-secundaria-de-ictus-actualizacion/#question-1
References
4. MacLean S, Mulla S, Akl EA, Jankowski M, Vandvik PO, Ebrahim S, et al. Patient values and preferences in decision making for antithrombotic therapy: a systematic review: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest [Online]. 2012 [accessed June 2021];141(2 Suppl):e1S-e23S. URL: https://doi.org/10.1378/chest.11-2290.
5. Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, et al. Antithrombotic therapy for atrial fibrillation: CHEST Guideline and Expert Panel Report. Chest [Online]. 2018 [accessed June 2021];154(5):1121-201. URL: https://doi.org/10.1016/j.chest.2018.07.040.
29. Paciaroni M, Agnelli G, Falocci N, Tsivgoulis G, Vadikolias K, Liantinioti C, et al. Early Recurrence and Major Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation Treated with Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study. J Am Heart Assoc [Online]. 2017 Nov [accessed June 2021];6(12):e007034. URL: https://doi.org/10.1161/jaha.117.007034.
33. Kodani E, Atarashi H, Inoue H, Okumura K, Yamashita T, Origasa H. Secondary prevention of stroke with warfarin in patients with nonvalvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry. J Stroke Cerebrovasc Dis [Online]. 2016 [accessed June 2021];25(3):585-99. URL: https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.11.020.
46. Oyagüez I, Suárez C, López-Sendón JL, González-Juanatey JR, de Andrés-Nogales F, Suárez J, Polanco C, Soto J. Cost-effectiveness analysis of apixaban versus edoxaban in patients with atrial fibrillation for stroke prevention. Pharmacoecon Open. 2020 Sep;4(3):485-497. URL: http://doi:10.1007/s41669-019-00186-7.
47. Rost NS, Giugliano RP, Ruff CT, Murphy SA, Crompton AE, Norden AD, et al. Outcomes with edoxaban versus warfarin in patients with previous cerebrovascular events: Findings from ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48). Stroke [Online]. 2016 Aug [accessed June 2021];47(8):2075- 82. URL: https://doi.org/10.1161/STROKEAHA.116.013540
Question
Recommendations
After analysing the evidence available on rivaroxaban compared to warfarin (given the lack of other comparators available such as acenocoumarol), the following recommendation was made:
In adult patients with an indication for the secondary prevention of stroke and non-valvular atrial fibrillation, we suggest using rivaroxaban rather than warfarin.
Key clinical considerations: the usual warnings and precautions for use listed in the summary of product characteristics were identified and special emphasis was placed on the need to check for adequate kidney function. There was insufficient evidence to make recommendations by subgroup, although there could be differences by sex and age.
Rationale
Below, we outline the rationale for one of the recommendations, highlighting the judgements of the GDG concerning the key criteria that justify the final recommendation.
The majority opinion in the GDG was that, in general, treatment with rivaroxaban has similar effects to that of treatment with warfarin for the secondary prevention of stroke in terms of the variables included in the analysis with the GRADE Evidence to Decision (EtD) framework and evidence profiles or tables. It was considered relevant to analyse certain variables associated with severe bleeding in patients with a history of stroke which had not previously been included. These variables were fatal bleeding (which could be considered “major bleeding”) and extracranial bleeding. In the case of the former, a relative risk (RR) of 0.98 (95% CI: 0.80–1.20) was observed with 44 cases per 1000 treated with rivaroxaban and 45 cases per 1000 treated with warfarin. For this reason, the GDG concluded that it could suggest treatment with rivaroxaban rather than warfarin in patients with a risk of bleeding (the majority of patients) .
Regarding the other variables, compared to warfarin, rivaroxaban for the secondary prevention of stroke had similar absolute effects (per 1000 patients treated, rivaroxaban being associated with 1 fewer case of stroke [95% CI: 9 fewer to 10 more strokes], 2 fewer cases of all-cause mortality [95% CI: 13 fewer to 10 more deaths], the same stroke-related mortality [95% CI: 3 fewer to 2 more] and 1 fewer case of vascular mortality [95% CI: 10 fewer to 10 more deaths]) and similar adverse effects (rivaroxaban being associated with 1 fewer case of severe bleeding [95% CI: 9 fewer to 10 more cases], 2 more cases of myocardial infarction [95% CI: 3 fewer to 9 more cases, and the same risk of systemic embolism). It should be highlighted that the assessment carried out by the methodology working group for this guideline considered that the studies included had limitations as a result of the risk of bias or imprecision while the GDG indicated that improvements in patients’ clinical condition and quality of life in clinical experience with this treatment supported the weak recommendation in favour.
Complete clinical question
For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/guia-de-practica-clinica-sobre-prevencion-secundaria-de-ictus-actualizacion/#question-1
References
5. Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, et al. Antithrombotic therapy for atrial fibrillation: CHEST Guideline and Expert Panel Report. Chest [Online]. 2018 [accessed June 2021];154(5):1121-201. URL: https://doi.org/10.1016/j.chest.2018.07.040.
29. Paciaroni M, Agnelli G, Falocci N, Tsivgoulis G, Vadikolias K, Liantinioti C, et al. Early Recurrence and Major Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation Treated with Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study. J Am Heart Assoc [Online]. 2017 Nov [accessed June 2021];6(12):e007034. URL: https://doi.org/10.1161/jaha.117.007034.
36. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke [Online]. 2018 Mar [accessed June 2021];49(3):e46-e110. URL: https://doi.org/10.1161/str.0000000000000158. Erratum in: Stroke. 2018 Mar;49(3):e138. Erratum in: Stroke. 2018 Apr 18; 49(6):e233-4.
37. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J [Online]. 2016 [accessed June 2021];37(38):2893-962. URL: https://doi.org/10.1093/eurheartj/ehw210
38. Wein T, Lindsay MP, Côté R, Foley N, Berlingieri J, Bhogal S et al. Canadian stroke best practice recommendations: Secondary prevention of stroke, sixth edition practice guidelines, update 2017. Int J Stroke [Online]. 2018 [accessed June 2021];13(4):420-43. URL: https://doi.org/10.1177/1747493017743062.
43. Monreal-Bosch M, Soulard S, Crespo C, Brand S, Kansal A. Comparación del coste-utilidad de los anticoagulantes orales de acción directa en la prevención de ictus en la fibrilación auricular no valvular en España. Rev Neurol. 2017;64(6):247-56.
48. Hankey GJ, Patel MR, Stevens SR, Becker RC, Breithardt G, Carolei A, et al. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol [Online]. 2012 Apr [accessed June 2021];11(4):315-22. URL: https://doi.org/10.1016/S1474-4422(12)70042-X.
49. Hong KS, Kwon SU, Lee SH, Lee JS, Kim YJ, Song TJ, et al. Rivaroxaban vs warfarin sodium in the ultra-early period after atrial fibrillation-related mild ischemic stroke: A randomized clinical trial. JAMA Neurol [Online]. 2017 Oct [accessed June 2021];74(10):1206-15. URL: https://doi.org/10.1001/jamaneurol.2017.2161.
50. Uchiyama S, Atarashi H, Inoue H, Kitazono T, Yamashita T, Shimizu W, et al. Primary and secondary prevention of stroke and systemic embolism with rivaroxaban in patients with non-valvular atrial fibrillation: Sub-analysis of the EXPAND Study. Heart Vessels [Online]. 2019 Jan [accessed June 2021];34(1):141-50. URL: https://doi.org/https://dx.doi.org/10.1007/s00380-018-1219-0
51. Hong KS, Lee SH, Kim EG, Cho KH, Chang DI, Rha JH, et al. Recurrent ischemic lesions after acute atherothrombotic stroke: clopidogrel plus aspirin versus aspirin alone. Stroke [Online]. 2016 [accessed June 2021];47:2323-30. URL: https://doi.org/10.1161/strokeaha.115.012293.
52. Lasek-Bal A, Urbanek T, Puz P, Piekarski M. Rivaroxaban in secondary cardiogenic stroke prevention: two-year single-centre experience based on follow-up of 209 patients. Kardiol Pol [Online]. 2016 [accessed June 2021];74(5):418-24. URL: https://doi.org/10.5603/kp.a2015.0207.
53. Canal Fontcuberta C, Betegón Nicolás L, Escolar Albadalejo C, De Salas-Cansado M, Rubio-Rodríguez D, Rubio-Terrés C. Análisis de coste-efectividad de apixabán frente a rivaroxabán en la prevención del ictus en pacientes con fibrilación auricular no valvular en España. Pharmaco Econ Span Res Artic. 2015;12(3):93-103. https://doi.org/10.1007/s40277-015-0041-7.
54. West A, Cox M, Zimmer LO, Fedder W, Weber C, Drew L, et al. An evaluation of stroke education in AVAIL registry hospitals. J Neurosci Nurs [Online]. 2012 [accessed June 2021];44(3):115-23. URL: https://doi.org/10.1097/JNN.0b013e3182510657.
55. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke [Online]. 2014 [accessed June 2021];45:2160-236. URL: https://doi.org/10.1161/STR.0000000000000024.
56. Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline from the American Heart Association/American Stroke Association. Stroke [Online]. 2021 Jul [accessed December 2021];52:e364-e467. URL: https://doi.org/10.1161/STR.0000000000000375. Erratum in: Stroke. 2021 Jul;52(7):e483-4.
57. Kotalczyk A, Lip GY, Calkins H. The 2020 ESC Guidelines on the Diagnosis and Management of Atrial Fibrillation. Arrhythm Electrophysiol Rev [Online]. 2021 Jul [accessed December 2021];10(2):65-7. URL: https://doi.org/10.15420/aer.2021.07
