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ETD2-2019

En personas con hipercolesterolemia e 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.

 1.- ¿El problema es una prioridad?
No Probablemente no Probablemente 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 personas con hipercolesterolemia e hipotiroidismo subclínico ¿Se debe usar levotiroxina en comparación a no usar?» fue priorizada por un panel de expertos en la materia. Ver detalle en Informe de Priorización de Preguntas de Práctica Clínica.

 2.- ¿Qué tan significativos son los efectos deseables anticipados?
Trivial Pequeño Moderado Grande Varía No lo sé

Triviales: Tomando en cuenta la evidencia identificada, la experiencia clínica y de las personas con el problema de salud, el equipo elaborador de la guía estimó que la magnitud de los efectos deseables de «usar levotiroxina» en comparación a «no usar» son triviales o no relevantes para las personas.

Evidencia de investigación

LEVOTIROXINA PARA PERSONAS CON HIPERCOLESTEROLEMIA E HIPOTIROIDISMO SUBCLÍNICO
Pacientes Personas con hipotiroidismo subclínico e hipercolesterolemia.
Intervención Usar levotiroxina.
Comparación No usar.

Desenlaces

Efecto relativo

(IC 95%)

Pacientes/ estudios

Efecto absoluto estimado*

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

SIN
 levotiroxina

CON
 levotiroxina

Diferencia

(IC 95%)

Mortalidad

(seguimiento a 12 meses)

RR 2,01
 (0,69 a 5,81)

737 pacientes/ 1 ensayo [79]

14
 por 1000

27 

por 1000

Diferencia: 13 más

(4 menos a 65 más)

image1,2

Muy baja

El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría aumentar la mortalidad. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

Eventos cardiovasculares**

RR 0,90
 (0,49 a 1,68)

737 pacientes/ 1 ensayo [79] 

54
 por 1000

49
 por 1000

Diferencia:
5 menos
 (28 menos a 37 más)

image1,2

Muy baja

El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en el riesgo de desarrollar eventos cardiovasculares. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

Niveles de LDL-C***

(seguimiento entre 5 y 12 meses)

320 pacientes/ 6 ensayos [19,20,24,30,32,34]

DME****: 0,31 menos
 (0,74 menos a 0,11 más)

image2,3,4

Muy baja

El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en los niveles de LDL-C. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

Calidad de vida

(seguimiento 3 a 12 meses)


 203 pacientes/ 3 ensayos [18,26,33]

DME****: 0,31 menos
 (0,87 menos a 0,25 más)

 

image2,3,4

Muy baja

El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en la calidad de vida. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

IC 95%: Intervalo de confianza del 95%. || RR: Riesgo relativo. || DME: Diferencia de media estandarizada.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo SIN levotiroxina está basado en el riesgo del grupo control en los estudios. El riesgo CON levotiroxina (y su intervalo de confianza) está calculado a partir del efecto relativo (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.
***Evaluado con LDL-C medido en mmol/l y mg/dl.
****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.
1 Se disminuyó dos niveles de certeza de la evidencia por tratarse de evidencia indirecta, ya que la evidencia utilizada proviene de un estudio cuyos participantes eran adultos de 74 años de edad promedio con hipotiroidismo subclínico, sin especificar perfil lipídico.
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 inconsistencia, dado que se observó heterogeneidad significativa (I2=71%).
4 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.

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Búsqueda y Síntesis de Evidencia

 3.- ¿Qué tan significativos son los efectos indeseables anticipados?
Grande Moderado Pequeño Trivial Varía No lo sé

Moderados: 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 de «usar levotiroxina» en comparación a «no usar» son moderados, y probablemente es importante para la mayoría de las personas.

Consideraciones Adicionales

El panel de expertos considera que la mortalidad podría aumentar.

Evidencia de investigación

LEVOTIROXINA PARA PERSONAS CON HIPERCOLESTEROLEMIA E HIPOTIROIDISMO SUBCLÍNICO
Pacientes Personas con hipotiroidismo subclínico e hipercolesterolemia.
Intervención Usar levotiroxina.
Comparación No usar.

Desenlaces

Efecto relativo

(IC 95%)

Pacientes/ estudios

Efecto absoluto estimado*

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

SIN
 levotiroxina

CON
 levotiroxina

Diferencia

(IC 95%)

Mortalidad

(seguimiento a 12 meses)

RR 2,01
 (0,69 a 5,81)

737 pacientes/ 1 ensayo [79]

14
 por 1000

27 

por 1000

Diferencia: 13 más

(4 menos a 65 más)

image1,2

Muy baja

El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría aumentar la mortalidad. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

Eventos cardiovasculares**

RR 0,90
 (0,49 a 1,68)

737 pacientes/ 1 ensayo [79] 

54
 por 1000

49
 por 1000

Diferencia:
5 menos
 (28 menos a 37 más)

image1,2

Muy baja

El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en el riesgo de desarrollar eventos cardiovasculares. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

Niveles de LDL-C***

(seguimiento entre 5 y 12 meses)

320 pacientes/ 6 ensayos [19,20,24,30,32,34]

DME****: 0,31 menos
 (0,74 menos a 0,11 más)

image2,3,4

Muy baja

El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en los niveles de LDL-C. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

Calidad de vida

(seguimiento 3 a 12 meses)


 203 pacientes/ 3 ensayos [18,26,33]

DME****: 0,31 menos
 (0,87 menos a 0,25 más)

 

image2,3,4

Muy baja

El tratamiento con levotiroxina en personas con hipotiroidismo subclínico e hipercolesterolemia podría tener poco impacto en la calidad de vida. Sin embargo, existe considerable incertidumbre dado que la certeza de la evidencia es muy baja.

IC 95%: Intervalo de confianza del 95%. || RR: Riesgo relativo. || DME: Diferencia de media estandarizada.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo SIN levotiroxina está basado en el riesgo del grupo control en los estudios. El riesgo CON levotiroxina (y su intervalo de confianza) está calculado a partir del efecto relativo (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.
***Evaluado con LDL-C medido en mmol/l y mg/dl.
****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.
1 Se disminuyó dos niveles de certeza de la evidencia por tratarse de evidencia indirecta, ya que la evidencia utilizada proviene de un estudio cuyos participantes eran adultos de 74 años de edad promedio con hipotiroidismo subclínico, sin especificar perfil lipídico.
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 inconsistencia, dado que se observó heterogeneidad significativa (I2=71%).
4 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.

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Búsqueda y Síntesis de Evidencia

 4.- ¿Cuál es la certeza general de la evidencia sobre efectos?
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
 (GRADE)

Mortalidad (seguimiento 12 meses)

CRITICO

◯◯◯
 MUY BAJA
a,b

Eventos cardiovasculares

CRITICO

◯◯◯
 MUY BAJA
a,b

Niveles de LDL-C (seguimiento entre 5 y 12 meses))

CRITICO

◯◯◯
 MUY BAJA
b,c,d

Eventos cardiovasculares (seguimiento 5 y 12 meses)

CRITICO

◯◯◯
 MUY BAJA
a,b,c,d

Calidad de vida

CRITICO

◯◯◯
 MUY BAJA
a,b,c

a. Se disminuyó dos niveles de certeza de la evidencia por tratarse de evidencia indirecta, ya que la evidencia utilizada proviene de un estudio cuyos participantes eran adultos de 74 años de edad promedio con hipotiroidismo subclínico, sin especificar perfil lipídico.
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 inconsistencia, dado que se observó heterogeneidad significativa (I2=71%).
d. 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.

 5.- ¿Hay incertidumbre importante o variabilidad sobre qué tanto valora la gente los desenlaces principales?
Variabilidad importantes Posiblemente hay incertidumbre o variabilidad importantes Probablemente no hay incertidumbre ni variabilidad importantes No hay variabilidad o incertidumbre importante

No 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 no existe variabilidad importante en como las personas, correctamente informadas, valoran los efectos deseables e indeseables de «usar levotiroxina».

Consideraciones Adicionales

El panel de expertos decidió no considerar la evidencia presentada ya que los resultados del estudio se relacionan con los síntomas del hipotiroidismo y no aborda exactamente la población con hipercolesterolemia e hipotiroidismo.

Búsqueda y Síntesis de Evidencia

 6.- El balance entre efectos deseables e indeseables favorece la intervención o la comparación?
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

Favorece la comparación: Tomando en cuenta la magnitud de los efectos deseables e indeseables , así como los valores y preferencias de las personas, el equipo elaborador de la guía consideró que «no usar» es la major alternativa.

 7.- ¿Qué tan grandes son los recursos necesarios (costos)?
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 “usar levotiroxina”, 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

Cantidad

Precio unitario

Precio anual de utilizar levotiroxina de 25ug

Precio anual de utilizar levotiroxina de 50ug

Precio anual de utilizar levotiroxina de 100ug

 

No realizar

Consulta médica electiva1

1

$9.610

$9.610

$9.610

$9.610

 

$9.610

Levotiroxina 25ug2

1 comp. De 25ug al día, permanente

365

$84

$30.660

 

levotiroxina 50ug2

1 comp. De 50ug al día, permanente

365

$86

$31.390

 

Levotiroxina 100ug2

1 comp. De 100ug al día, permanente

365

$11

$4.015

 

TOTAL

$40.270

$41.000

$13.625

 

$9.610

(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

 8.- ¿La costo-efectividad de la intervención beneficia la intervención o la comparación?
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

 9.- ¿Cuál sería el impacto en equidad en salud?
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.

 10.- ¿La intervención es aceptable para las partes interesadas?
No Probablemente no Probablemente sí Varía No lo sé

No: El equipo elaborador de la guía consideró que »usar levotiroxina» NO es aceptable para las partes interesadas (profesionales de la salud, gestores de centros de salud, directivos de centros de salud, pacientes, cuidadores, seguros de salud, otros).

 11.- ¿Es factible implementar la intervención?
No Probablemente no Probablemente 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» .