“Increased risk of thrombosis in antiphospholipid síndrome patients treated with direct oral anticoagulants. Results from international patient-level data metaanálisis Autoinmunity Reviews.” 1
Background: Direct oral anticoagulants (DOACs) are widely used for secondary prevention of venous thromboembolism (VTE) but their clinical efficacy and safety are not established in Antiphospholipid Syndrome (APS) patients. There is only one randomized controlled trial published while others are still ongoing. Many nonrandomized studies have been published in this field with conflicting opinions.
Purpose of review: We conducted a systematic review using MEDLINE, EMBASE and Cochrane databases from 2000 until March 2018 regarding APS patients treated with DOACs. We performed a patient-level data metaanalysis to a) estimate the prevalence of recurrent thrombosis in APS patients treated with DOACs in the literature, and b) identify variables associated with recurrent thrombosis.
Results: We identified 47 studies corresponding to 447 APS patients treated with DOACs. Three commercially available DOACs were analyzed: rivaroxaban (n=290), dabigatran etexilate (n=144) and apixaban (n=13). A total of 73 out of 447 patients (16%) experienced a recurrent thrombosis while on DOACs with a mean duration until thrombosis of 12.5 months. Rates of recurrent thromboses were 16.9% and 15% in APS patients receiving either anti-Xa inhibitors or dabigatran respectively. Triple positivity (positivity for all three antiphospholipid antibodies) was associated with a four fold increased risk of recurrent thrombosis (56% vs 23%; OR=4.3 [95%CI; 2.3–7.7], p < 0.0001) as well as a higher number of clinical criteria for APS classification. In patients treated with anti-Xa inhibitors, history of arterial thrombosis was associated with a higher risk of recurrent thrombosis (32% vs 14%; OR=2.8 [95%CI; 1.4–5.7], p=0.006).
In conclusion, DOACs are not effective in all APS patients and should not be used routinely in these patients. Randomized controlled trials assessing clinical efficacy and safety as primary endpoints are underway. In the meantime, a registry of APS patients on DOACs could be proposed to establish in which APS subgroups DOACs would be a safe alternative to warfarin.
Comentario
Los anticoagulantes orales directos se utilizan ampliamente para la prevención secundaria del tromboembolismo venoso, pero su eficacia clínica y su seguridad no están establecidas en pacientes con síndrome antifosfolípido (SAF). Solo hay un ensayo controlado aleatorio publicado, mientras que otros aún están en curso. Muchos estudios no aleatorios se han publicado en este campo con opiniones contradictorias.Se realizó una revisión sistemática utilizando las bases de datos MEDLINE, EMBASE y Cochrane desde 2000 hasta marzo de 2018 con respecto a los pacientes con SAF tratados con ACODs. Se realizó un metaanálisis de datos para estimar la prevalencia de trombosis recurrente e identificar variables asociadas con la recurrencia de trombosis. Se identificaron 47 estudios correspondientes a 447 pacientes. Se analizaron tres ACODs: rivaroxabán (n = 290), dabigatrán (n = 144) y apixabán (n = 13). Un total de 73 pacientes (16%) experimentó una trombosis recurrente mientras estaba en tratamiento con ACOD, con un tiempo medio hasta la trombosis de 12,5 meses. Las tasas de trombosis recurrentes fueron de 16.9% y 15% en pacientes que recibieron inhibidores anti-Xa o dabigatrán respectivamente. La triple positividad se asoció con un riesgo cuatro veces mayor de trombosis recurrente, así como a mayor número de criterios clínicos para la clasificación SAF. En pacientes tratados con inhibidores anti-Xa, el antecedente de trombosis arterial se asoció con un mayor riesgo de trombosis recurrente (32% frente a 14%; OR = 2,8 [IC del 95%; 1,4-5,7], p = 0,006). En conclusión, los ACODs no son eficaces en todos los pacientes con SAF y no deben usarse de manera rutinaria en estos pacientes. Mientras dispongamos de resultados de los ensayos clínicos en marcha, sería importante proponer un registro de pacientes con SAF y ACOD para establecer en qué subgrupos serían una alternativa segura a la warfarina.
- Dufrost V, Risse J, Reshetnyak T, Satybaldyeva, Du Y. Increased risk of thrombosis in antiphospholipid síndrome patients treated with direct oral anticoagulants. Results from international patient-level data metaanálisis. Autoinmunity Reviews 2018;17:1011-1021
