ETD8-2019
En personas mayores de 65 años con hipotiroidismo subclínico el Ministerio de Salud SUGIERE no tratar con levotiroxina
El problema ha sido definido como prioritario en el marco de las Garantías Explícitas en Salud (GES), régimen integral de salud que prioriza un grupo de patologías o problemas de salud, garantizando el acceso a tratamiento oportuno y de calidad.
A continuación se presenta la “Tabla de la evidencia a la decisión” con el resumen de los juicios, la evidencia de investigación evaluada, consideraciones adicionales y comentarios planteados por el panel.
| No | Probablemente no | Probablemente sí | Sí | Varía | No lo sé |
|---|
El problema o condición de salud abordado en la pregunta ha sido definido como prioritario en el marco de las Garantías Explícitas en Salud (GES), régimen integral de salud que prioriza un grupo de patologías o problemas de salud, garantizando el acceso a tratamiento oportuno y de calidad. Además, particularmente, la pregunta «En adultos con hipotiroidismo subclínico ¿Se debe “tratar con levotiroxina” en comparación a “no tratar? fue priorizada por un panel de expertos en la materia. Ver detalle en Informe de Priorización de Preguntas de Práctica Clínica.
| Trivial | Pequeño | Moderado | Grande | Varía | No lo sé |
|---|
Pequeños: Tomando en cuenta la evidencia identificada, la experiencia clínica y la vivencia de las personas con el problema de salud, el equipo elaborador de la guía estimó que la magnitud de los efectos deseables «usar levotiroxina» en comparación a «no usar » es pequeña, aunque podría ser importante para algunas personas
Consideraciones Adicionales
El panel de expertos considera que la evidencia presentada no demuestra beneficios importantes en el grupo de personas tratado con levotiroxina.
Evidencia de investigación
LEVOTIROXINA EN ADULTOS CON HIPOTIROIDISMO SUBCLÍNICO.
Pacientes Adultos con hipotiroidismo subclínico.
Intervención Levotiroxina.
Comparación No tratar.
|
Desenlaces |
Efecto relativo (IC 95%) — Estudios/ pacientes |
Efecto absoluto estimado* |
Certeza de la evidencia (GRADE) |
Mensajes clave en términos sencillos |
||
|
SIN levotiroxina |
CON levotiroxina |
Diferencia (IC 95%) |
||||
|
Mortalidad por cualquier causa |
RR 2,01 — 1 ensayo [47] /737 pacientes |
14 |
27 por 1000 |
Diferencia: 13 más (4 menos a 65 más) |
Muy baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría aumentar la mortalidad. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
|
Eventos cardiovasculares ** |
RR 0,90 — 1 ensayo [47] /737 pacientes |
54 |
49 |
Diferencia: |
Muy baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría tener poco impacto en el desarrollo de eventos cardiovasculares. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
|
Calidad de vida*** (3 a 12 meses) |
— 5 ensayos [28, 29, 44, 45, 47] /896 pacientes
|
DME: 0,11 (Margen de error: 0,4 menor a 0,18 más) |
Baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría tener poco impacto en la calidad de vida. |
||
|
Efectos adversos**** |
Sólo dos ensayos que incluyeron 57 pacientes reportaron efectos adversos [27,41]. Sin embargo, no se identificaron diferencias significativas entre los grupos: uno de ellos [41] reportó que 2 participantes pertenecientes al grupo de intervención tuvieron que abandonar el estudio por un empeoramiento de las palpitaciones y el otro ensayo [27] reportó 3 efectos adversos en el grupo de intervención y 2 en el grupo de control. |
Baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría tener un bajo riesgo de efectos adversos. |
|||
|
Síntomas relacionados a la tiroides*** (6 a 12 meses) |
— 3 ensayos [34,45,47] /874 pacientes
|
DME: 0 (Margen de error: 0,15 menor a 0,15 más) |
Baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría tener poco impacto en los síntomas relacionados a la tiroides. |
||
|
Síntomas depresivos ***** (3 a 12 meses) |
— 3 ensayos [28,40,45] /200 pacientes
|
3,3 puntos |
3,9 puntos |
DM: 0,6 más |
Moderada |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico probablemente tiene poco impacto en los síntomas depresivos. |
IC 95%: Intervalo de confianza del 95%. || RR: Riesgo relativo. || DM: Diferencia de media. || DME: Diferencia de media estandarizada.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo/promedio SIN levotiroxina está basado en el riesgo/promedio del grupo control en los estudios. El riesgo/promedio CON levotiroxina (y su intervalo de confianza) está calculado a partir del efecto relativo/diferencia de medias (y su intervalo de confianza).
** Incluye eventos cardiovasculares fatales y no fatales, tales como infarto agudo al miocardio, accidente cerebrovascular, amputaciones, revascularización por aterosclerosis vascular, entre otros.
*** La diferencia media estandarizada se utiliza cuando el desenlace ha sido medido en diferentes escalas, siendo difícil su interpretación clínica. Comúnmente se acepta que valores cercanos a 0,2 tendrían poca relevancia clínica, valores de 0,5 tendrían relevancia moderada (se reconoce clínicamente) y valores superiores a 0,8 tendrían relevancia alta.
**** Los efectos adversos observados fueron angina, fibrilación auricular, gota, palpitaciones y accidente cerebrovascular.
***** Evaluado con escala BDI (Beck Depression Inventory), que va de 0 a 63 puntos, donde mayor puntaje indica mayor presencia de síntomas depresivos.
1 Se disminuyó dos niveles de certeza de la evidencia por tratarse de evidencia indirecta, ya que toda o la mayoría de la evidencia proviene de un ensayo que contempla una población de 74 años de edad promedio. El desenlace calidad de vida no fue penalizado debido a que este ensayo sólo aporta un 33% a la estimación del efecto.
2 Se disminuyó un nivel de certeza de la evidencia por imprecisión, debido a que a cada extremo del intervalo de confianza se tomarían decisiones diferentes.
3 Se disminuyó un nivel de certeza de la evidencia por riesgo de sesgo, debido a que en la mayoría de los ensayos no estaba clara la generación ni el ocultamiento de la secuencia de aleatorización y se observaron limitaciones en el enmascaramiento de los participantes.
4 Se disminuyó un nivel de certeza de la evidencia por inconsistencia, debido a que se observó heterogeneidad significativa (I2= 60%).
Fecha de elaboración de la tabla: Julio, 2019
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Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de efectos deseables e indeseables
| Grande | Moderado | Pequeño | Trivial | Varía | No lo sé |
|---|
Pequeños: Tomando en cuenta la evidencia identificada, la experiencia clínica y la vivencia de las personas con el problema de salud, el equipo elaborador de la guía estimó que la magnitud de los efectos indeseables «usar levotiroxina» en comparación a «no usar» es pequeña, aunque podría ser importante para algunas personas
Consideraciones Adicionales
El panel de expertos considera que si las dosis de levotiroxina son adecuadas el riesgo de desarrollar efectos adversos es bajo.
Evidencia de investigación
LEVOTIROXINA EN ADULTOS CON HIPOTIROIDISMO SUBCLÍNICO.
Pacientes Adultos con hipotiroidismo subclínico.
Intervención Levotiroxina.
Comparación No tratar.
|
Desenlaces |
Efecto relativo (IC 95%) — Estudios/ pacientes |
Efecto absoluto estimado* |
Certeza de la evidencia (GRADE) |
Mensajes clave en términos sencillos |
||
|
SIN levotiroxina |
CON levotiroxina |
Diferencia (IC 95%) |
||||
|
Mortalidad por cualquier causa |
RR 2,01 — 1 ensayo [47] /737 pacientes |
14 |
27 por 1000 |
Diferencia: 13 más (4 menos a 65 más) |
Muy baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría aumentar la mortalidad. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
|
Eventos cardiovasculares ** |
RR 0,90 — 1 ensayo [47] /737 pacientes |
54 |
49 |
Diferencia: |
Muy baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría tener poco impacto en el desarrollo de eventos cardiovasculares. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja. |
|
Calidad de vida*** (3 a 12 meses) |
— 5 ensayos [28, 29, 44, 45, 47] /896 pacientes
|
DME: 0,11 (Margen de error: 0,4 menor a 0,18 más) |
Baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría tener poco impacto en la calidad de vida. |
||
|
Efectos adversos**** |
Sólo dos ensayos que incluyeron 57 pacientes reportaron efectos adversos [27,41]. Sin embargo, no se identificaron diferencias significativas entre los grupos: uno de ellos [41] reportó que 2 participantes pertenecientes al grupo de intervención tuvieron que abandonar el estudio por un empeoramiento de las palpitaciones y el otro ensayo [27] reportó 3 efectos adversos en el grupo de intervención y 2 en el grupo de control. |
Baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría tener un bajo riesgo de efectos adversos. |
|||
|
Síntomas relacionados a la tiroides*** (6 a 12 meses) |
— 3 ensayos [34,45,47] /874 pacientes
|
DME: 0 (Margen de error: 0,15 menor a 0,15 más) |
Baja |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico podría tener poco impacto en los síntomas relacionados a la tiroides. |
||
|
Síntomas depresivos ***** (3 a 12 meses) |
— 3 ensayos [28,40,45] /200 pacientes
|
3,3 puntos |
3,9 puntos |
DM: 0,6 más |
Moderada |
El tratamiento con levotiroxina en adultos con hipotiroidismo subclínico probablemente tiene poco impacto en los síntomas depresivos. |
IC 95%: Intervalo de confianza del 95%. || RR: Riesgo relativo. || DM: Diferencia de media. || DME: Diferencia de media estandarizada.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo/promedio SIN levotiroxina está basado en el riesgo/promedio del grupo control en los estudios. El riesgo/promedio CON levotiroxina (y su intervalo de confianza) está calculado a partir del efecto relativo/diferencia de medias (y su intervalo de confianza).
** Incluye eventos cardiovasculares fatales y no fatales, tales como infarto agudo al miocardio, accidente cerebrovascular, amputaciones, revascularización por aterosclerosis vascular, entre otros.
*** La diferencia media estandarizada se utiliza cuando el desenlace ha sido medido en diferentes escalas, siendo difícil su interpretación clínica. Comúnmente se acepta que valores cercanos a 0,2 tendrían poca relevancia clínica, valores de 0,5 tendrían relevancia moderada (se reconoce clínicamente) y valores superiores a 0,8 tendrían relevancia alta.
**** Los efectos adversos observados fueron angina, fibrilación auricular, gota, palpitaciones y accidente cerebrovascular.
***** Evaluado con escala BDI (Beck Depression Inventory), que va de 0 a 63 puntos, donde mayor puntaje indica mayor presencia de síntomas depresivos.
1 Se disminuyó dos niveles de certeza de la evidencia por tratarse de evidencia indirecta, ya que toda o la mayoría de la evidencia proviene de un ensayo que contempla una población de 74 años de edad promedio. El desenlace calidad de vida no fue penalizado debido a que este ensayo sólo aporta un 33% a la estimación del efecto.
2 Se disminuyó un nivel de certeza de la evidencia por imprecisión, debido a que a cada extremo del intervalo de confianza se tomarían decisiones diferentes.
3 Se disminuyó un nivel de certeza de la evidencia por riesgo de sesgo, debido a que en la mayoría de los ensayos no estaba clara la generación ni el ocultamiento de la secuencia de aleatorización y se observaron limitaciones en el enmascaramiento de los participantes.
4 Se disminuyó un nivel de certeza de la evidencia por inconsistencia, debido a que se observó heterogeneidad significativa (I2= 60%).
Fecha de elaboración de la tabla: Julio, 2019
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Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de efectos deseables e indeseables
| Muy baja | Baja | Moderada | Alta | Ningún estudio incluido |
|---|
Muy Baja: Existe considerable incertidumbre de que la evidencia identificada es suficiente para apoyar una recomendación determinada, dado que existen muy pocos estudios o estos tienen limitaciones importantes.
Evidencia de investigación
|
Desenlaces |
Importancia |
Certainty of the evidence |
|
Mortalidad por cualquier causa |
CRÍTICO |
⨁◯◯◯ |
|
Eventos cardiovasculares |
CRÍTICO |
⨁◯◯◯ |
|
Calidad de vida (3 a 12 meses) |
CRÍTICO |
⨁⨁◯◯ |
|
Efectos adversos |
CRÍTICO |
⨁⨁◯◯ |
|
Síntomas relacionados a la tiroides (6 a 12 meses) |
CRÍTICO |
⨁⨁◯◯ |
|
Síntomas depresivos |
CRÍTICO |
⨁⨁⨁◯ |
a. Se disminuyó dos niveles de certeza de la evidencia por tratarse de evidencia indirecta, ya que toda o la mayoría de la evidencia proviene de un ensayo que contempla una población de 74 años de edad promedio. El desenlace calidad de vida no fue penalizado debido a que este ensayo sólo aporta un 33% a la estimación del efecto
b. Se disminuyó un nivel de certeza de la evidencia por imprecisión, debido a que a cada extremo del intervalo de confianza se tomarían decisiones diferentes
c. Se disminuyó un nivel de certeza de la evidencia por riesgo de sesgo, debido a que en la mayoría de los ensayos no estaba clara la generación ni el ocultamiento de la secuencia de aleatorización y se observaron limitaciones en el enmascaramiento de los participantes
d. Se disminuyó un nivel de certeza de la evidencia por inconsistencia, debido a que se observó heterogeneidad significativa (I2= 60%).
| Variabilidad importantes | Probablemente hay variabilidad importante | Probablemente no hay incertidumbre ni variabilidad importantes | No hay variabilidad o incertidumbre importante |
|---|
Probablemente hay variabilidad importante: Tomando en cuenta la evidencia identificada, la experiencia clínica y la vivencia de las personas con el problema de salud, el equipo elaborador de la guía consideró que probablemente existe variabilidad en como las personas, correctamente informadas, podrían valorar los efectos deseables e indeseables de » usar levotiroxina».
Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de valores y preferencias de los pacientes
| Favorece la comparación | Probablemente favorece la comparación | No favorece la intervención ni la comparación | Probablemente favorece la intervención | Favorece la intervención | Varía | No lo sé |
|---|
Probablemente favorece la comparación: Tomando en cuenta la magnitud de los efectos deseables e indeseables, asi como los valores y preferencias de las personas, el equipo elaborador de la guía consideró que «no usar» probablemente es la mejor alternativa en la mayoria de las situaciones, aunque pudieran haber escenarios donde se justifique «usar levotiroxina».
| Costos extensos | Costos moderados | Costos y ahorros pequeños | Ahorros moderados | Ahorros extensos | Varía | No lo sé |
|---|
Costos y ahorros pequeños: La diferencia del costo o ahorros entre » usar levotiroxina » y »no usar» es inferior a $674.672. Por lo cual el equipo elaborador de la guía consideró que implementar » usar levotiroxina » no significaría un cambio importante en el gasto o ahorro del sistema de salud.
Evidencia de investigación
A continuación se muestran los costos referenciales de la prestación sanitaria “tratar con levotiroxina y de no tratar”, de modo que el equipo elaborador de la Guía se pudiese pronunciar al respecto y no debe ser utilizado para otros fines.
Tabla N° 1 Precios referenciales
|
Ítem |
Posología |
Precio unitario |
Cantidad |
Precio de tratar con levotiroxina |
Precio de no tratar |
|
Consulta médica electiva1 |
– |
$9.610 |
1 |
$9.610 |
$9.610 |
|
levotiroxina2 |
1 comp de 50ug al día, permanente |
$86 |
365 |
$31.390 |
– |
|
|
|
|
|
$41.000 |
$9.610 |
Fuente:
(1) Precio Total para prestador Nivel 3 obtenido de Arancel FONASA Modalidad Libre Elección (MLE) 2019
(2) Precio de compra por Establecimiento de Salud Público a través de plataforma Mercado Público 2019 (Incluye IVA)
Búsqueda y Síntesis de Evidencia
Búsqueda de costos
| Favorece la comparación | Probablemente favorece la comparación | No favorece la intervención ni la comparación | Probablemente favorece la intervención | Favorece la intervención | Varía | Ningún estudio incluido |
|---|
Ningún estudio incluido: No se identificaron estudios evaluando costo-efectividad.
Búsqueda y Síntesis de Evidencia
Informe de búsqueda y síntesis de costo-efectividad
| Reducido | Probablemente reducido | Probablemente ningún impacto | Probablemente aumentado | Aumentado | Varía | No lo sé |
|---|
Probablemente ningún impacto: El equipo elaborador de la guía consideró que esta recomendación probablemente no tendría ningún impacto en la equidad en salud, dado que que en la actualidad existe amplio acceso a ambas alternativas, ya sea en términos económicos, geográficos u otros.
| No | Probablemente no | Probablemente sí | Sí | Varía | No lo sé |
|---|
Varía: El equipo elaborador de la guía considera que la aceptabilidad de »usar levotiroxina» es variable en distintos contextos o para distintos tomadores de decisión.
Consideraciones Adicionales
El panel de expertos considera que el uso de esta terapia pudiese variar de acuerdo a los tratantes y también podría haber variabilidad en la elección de las personas.
| No | Probablemente no | Probablemente sí | Sí | Varía | No lo sé |
|---|
Sí: Tomando en cuenta la capacidad de la red asistencial y los recursos humanos y materiales disponibles, el equipo elaborador de la guía consideró que SI es factible implementar »usar levotiroxina» .