Clinical Practice Guideline for the secondary prevention of stroke. Update
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Question
Recommendations
After analysing the evidence available regarding PFO plus antiplatelet therapy instead of anticoagulation for the secondary prevention of stroke, the following recommendation was made (given the lack of individual comparators in the literature meeting the proposed criteria for inclusion and prioritisation):
In patients under 60 years old with cryptogenic stroke or TIA (both embolic in nature), we suggest using PFO closure plus antiplatelet therapy instead of anticoagulation for the secondary prevention of stroke.
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 experts considered that opting for PFO closure followed by antiplatelet therapy instead of the use of anticoagulation treatment may have little or no impact on stroke recurrence (1.6% of events in 5 years) and would probably reduce the occurrence of major bleeding (2.0% of events in 5 years). Further, they considered that it may have little or no impact on rates of all-cause mortality, TIA, and systemic embolism.
The results observed in terms of absolute values showed that PFO closure plus antiplatelet therapy was associated with 20 fewer episodes of major bleeding per 1000 patients treated with anticoagulation (95% CI: 27 fewer to 2 more episodes). The odds ratio was 0.26 (95% CI: 0.07 – 0.82). For other key variables (TIA, all-cause mortality, and systemic embolism), the absolute values all had confidence intervals that included the null value, and hence, no statistically significant differences were observed between the treatments.
Therefore, the GDG considered that PFO closure plus antiplatelet therapy reduced the risk of major bleeding compared to anticoagulation, although there would not be significant benefits in terms of reduction in the risk of stroke or TIA.
The weak recommendation in favour of the intervention or suggestion to perform PFO closure followed by antiplatelet therapy in the context of the Spanish National Health System was the result of the balance of the health effects likely favouring the intervention, taking into account the values and preferences of patients, who rated all the variables as critical and manifested their preference for stroke prevention over other variables, and also considering it to be a relevant issue that anticoagulant therapy needs monitoring.
Regarding the outcomes of stroke recurrence and all-cause mortality, the confidence in the evidence was rated as low, and therefore, the effect observed in the study is likely to be substantially different from the true effect. For the outcomes of severe bleeding, TIA, and systemic embolism, the confidence in the evidence was considered moderate.
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-2
References
58. Mir H, Siemieniuk RAC, Cruz Ge L, Foroutan F, Fralick M, Syed T, et al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation in patients with patent foramen ovale and cryptogenic stroke: a systematic review and network meta-analysis incorporating complementary external evidence. BMJ Open [Online]. 2018 Jul [accessed June 2021];8(7):e023761. URL: https://doi.org/10.1136/bmjopen-2018-023761. Erratum in: BMJ Open. 2018 Aug 17;8(8):e023761corr1.
59. Messé S, Gronseth G, Kizer J, Homma S, Rosterman L, Carroll Ishida J, et al. Practice advisory update summary: Patent foramen ovale and secondary stroke prevention. Report of the Guideline Subcommittee of the American Academy of Neurology. Neurology [Online]. 2020 [accessed June 2021];94(20):876-85. URL: https://doi.org/10.1212/WNL.0000000000009443.
60. Madhkour R, Meier B. PFO and Cryptogenic Stroke: When should it be closed? Rev Esp Cardiol (Engl Ed) [Online]. 2019 [accessed June 2021];72(5):369- URL: https://doi.org/10.1016/j.rec.2018.11.004.
61. Serena J, Dávalos A. [Patent foramen ovale and cryptogenic stroke: where to go from here]. Rev Esp Cardiol [Online]. 2003 Jul [accessed June 2021];56(7):649-51. URL: https://doi.org/10.1016/s0300-8932(03)76933-4.
Question
Recommendations
After analysing the evidence available on PFO closure plus antiplatelet therapy compared to antiplatelets alone for the secondary prevention of stroke in adult patients with PFO, the following recommendation was made:
We suggest using closure of PFO plus antiplatelet therapy instead of antiplatelet therapy alone in patients under 60 years of age with stroke or cryptogenic TIA (both embolic in nature) in whom the most plausible cause of these events is the PFO.
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 weak recommendation for the intervention (PFO closure followed by antiplatelet therapy) in the context of the Spanish National Health Service was the result of weighing the health effects (it being considered that the balance was in favour of the intervention) as well as the values and preferences of patients (who preferred prevention of stroke over prevention of other complications).
A reference study (Mir et al. 2018) found that PFO closure plus antiplatelet therapy was associated with an 8.7% reduction in the risk of stroke recurrence after 3.8 years, and with a 0.6% increase in all-cause mortality and a 0.6% decrease in TIA over the 3.8 years of follow-up58. Regarding adverse events, fewer cases of severe bleeding (0.7%) and systemic embolism (0.1%) were observed in patients treated with PFO closure plus antiplatelet therapy, over the 3.8-year follow-up. The confidence in the results observed (available evidence) was considered moderate, in favour of the intervention (PFO closure plus antiplatelet therapy), although limited due to the occurrence of serious intervention-related adverse events. In general, it was considered that although the use of a closure device would be associated with higher costs, this would be compensated for in the long term by a reduction in the rate of recurrence. Closure of PFO plus antiplatelet therapy seems feasible and would probably be accepted by the target population due to a reduction in the risk of stroke recurrence.
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-2
References
58. Mir H, Siemieniuk RAC, Cruz Ge L, Foroutan F, Fralick M, Syed T, et al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation in patients with patent foramen ovale and cryptogenic stroke: a systematic review and network meta-analysis incorporating complementary external evidence. BMJ Open [Online]. 2018 Jul [accessed June 2021];8(7):e023761. URL: https://doi.org/10.1136/bmjopen-2018-023761. Erratum in: BMJ Open. 2018 Aug 17;8(8):e023761corr1.
59. Messé S, Gronseth G, Kizer J, Homma S, Rosterman L, Carroll Ishida J, et al. Practice advisory update summary: Patent foramen ovale and secondary stroke prevention. Report of the Guideline Subcommittee of the American Academy of Neurology. Neurology [Online]. 2020 [accessed June 2021];94(20):876-85. URL: https://doi.org/10.1212/WNL.0000000000009443.
61. Serena J, Dávalos A. [Patent foramen ovale and cryptogenic stroke: where to go from here]. Rev Esp Cardiol [Online]. 2003 Jul [accessed June 2021];56(7):649-51. URL: https://doi.org/10.1016/s0300-8932(03)76933-4.
62. Kasner S, Rhodes J, Iversen H, Nielsen-Kudsk J, Settergren M, Sjöstrand C, et al. Fiveyear outcomes of PFO closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med [Online]. 2021 [accessed June 2021];384:970-1. URL: https://doi.org/10.1056/nejmc2033779.
Question
Recommendations
After analysing the evidence available on anticoagulant compared to antiplatelet therapy for the secondary prevention of stroke in adult patients with PFO, the following recommendation was made:
In patients opting for medical treatment alone, without PFO closure, we suggest either antiplatelet or anticoagulation therapy, given that the result of the comparison indicates that the two types of treatment have similar effects.
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.
In patients with cryptogenic stroke and PFO, no differences were found between the use of anticoagulation and antiplatelet therapy in terms of desirable effects (reduction in the risk of stroke and TIA) or in the occurrence of adverse effects (bleeding or major bleeding), and hence, there was no basis for recommending anticoagulation over antiplatelet therapy. Further, it was observed that there was probably little or no difference in the rates of mortality, TIA or systemic embolism (evidence of moderate/low quality).
The low confidence in the evidence and variability in the values and preferences of patients reduce the confidence in the results.
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-2
References
58. Mir H, Siemieniuk RAC, Cruz Ge L, Foroutan F, Fralick M, Syed T, et al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation in patients with patent foramen ovale and cryptogenic stroke: a systematic review and network meta-analysis incorporating complementary external evidence. BMJ Open [Online]. 2018 Jul [accessed June 2021];8(7):e023761. URL: https://doi.org/10.1136/bmjopen-2018-023761. Erratum in: BMJ Open. 2018 Aug 17;8(8):e023761corr1.
59. Messé S, Gronseth G, Kizer J, Homma S, Rosterman L, Carroll Ishida J, et al. Practice advisory update summary: Patent foramen ovale and secondary stroke prevention. Report of the Guideline Subcommittee of the American Academy of Neurology. Neurology [Online]. 2020 [accessed June 2021];94(20):876-85. URL: https://doi.org/10.1212/WNL.0000000000009443.
63. Ceresetto JM. Anticoagulación en Pacientes con Foramen Oval Permeable. Rev Argentina hematol. 2007; Supl I: 6-11.
