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Cochrane Database of Systematic Reviews

Intervenciones farmacológicas para la hipertensión en niños

Información

DOI:
https://doi.org/10.1002/14651858.CD008117.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 01 febrero 2014see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:

  1. Grupo Cochrane de Hipertensión

Copyright:
  1. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

  • Swasti Chaturvedi

    Correspondencia a: Department of Paediatrics, Christian Medical College, Vellore, India

    [email protected]

  • Deborah H Lipszyc

    Institute of Medical Science, Hospital for Sick Children, Toronto, Canada

  • Christoph Licht

    Department of Nephrology, Hospital for Sick Children, Toronto, Canada

  • Jonathan C Craig

    Sydney School of Public Health, The University of Sydney, Sydney, Australia

  • Rulan Parekh

    Department of Paediatrics, Hospital for Sick Children, Toronto, Canada

Contributions of authors

Swasti Chaturvedi formulated the idea and developed the basis for the protocol. She took a lead role in searching, identifying and assessing studies, data extraction and analysis, and writing up the final review.

Deborah Lipszyc helped in identifying and assessing studies, double‐checking the data extraction and the 'Risk of bias' assessment. She also participated in writing up the final review.

Christoph Licht participated in writing up the review.

Jonathan Craig helped in resolving any disagreement and completion ofthe review.

Rulan Parekh participated in developing the protocol, assessment of studies, data extraction and analysis, and in completing the final manuscript.

Sources of support

Internal sources

  • Hospital for Sick Children, Toronto, Canada.

External sources

  • No sources of support supplied

Declarations of interest

None known.

Acknowledgements

The authors would like to acknowledge the help provided by the Cochrane Hypertension Group and Ms Miranda Cumpston from the Australasian Cochrane Centre.

Version history

Published

Title

Stage

Authors

Version

2014 Feb 01

Pharmacological interventions for hypertension in children

Review

Swasti Chaturvedi, Deborah H Lipszyc, Christoph Licht, Jonathan C Craig, Rulan Parekh

https://doi.org/10.1002/14651858.CD008117.pub2

2009 Oct 07

Pharmacological interventions for essential hypertension in children

Protocol

Swasti Chaturvedi, Christoph Licht, Rulan Parekh, Jonathan C Craig

https://doi.org/10.1002/14651858.CD008117

Differences between protocol and review

Changed protocol from pharmacological interventions for primary hypertension to include pharmacological interventions for both primary and secondary causes of hypertension, given the paucity of trials for primary hypertension.

Deborah Lipszyc was added as an author. She helped in identifying and assessing studies, double‐checking the data extraction and the 'Risk of bias' assessment. She also participated in writing up the final review.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Adolescent; Child; Humans;

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow diagram.
Figuras y tablas -
Figure 1

Study flow diagram.

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'Risk of bias' graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

'Risk of bias' graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
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Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

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Forest plot of comparison: 1 Antihypertensive drug class versus placebo, outcome: 1.1 Systolic blood pressure.
Figuras y tablas -
Figure 4

Forest plot of comparison: 1 Antihypertensive drug class versus placebo, outcome: 1.1 Systolic blood pressure.

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Forest plot of comparison: 1 Antihypertensive drug class versus placebo, outcome: 1.2 Diastolic blood pressure.
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Figure 5

Forest plot of comparison: 1 Antihypertensive drug class versus placebo, outcome: 1.2 Diastolic blood pressure.

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Forest plot of comparison: 2 Drug different doses, outcome: 2.1 SBP.
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Figure 6

Forest plot of comparison: 2 Drug different doses, outcome: 2.1 SBP.

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Forest plot of comparison: 2 Drug different doses, outcome: 2.2 DBP.
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Figure 7

Forest plot of comparison: 2 Drug different doses, outcome: 2.2 DBP.

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Comparison 1 Antihypertensive drug class versus placebo, Outcome 1 Systolic blood pressure.
Figuras y tablas -
Analysis 1.1

Comparison 1 Antihypertensive drug class versus placebo, Outcome 1 Systolic blood pressure.

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Comparison 1 Antihypertensive drug class versus placebo, Outcome 2 Diastolic blood pressure.
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Analysis 1.2

Comparison 1 Antihypertensive drug class versus placebo, Outcome 2 Diastolic blood pressure.

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Comparison 2 Antihypertensive drug dose response, Outcome 1 Systolic blood pressure.
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Analysis 2.1

Comparison 2 Antihypertensive drug dose response, Outcome 1 Systolic blood pressure.

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Comparison 2 Antihypertensive drug dose response, Outcome 2 Diastolic blood pressure.
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Analysis 2.2

Comparison 2 Antihypertensive drug dose response, Outcome 2 Diastolic blood pressure.

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Summary of findings for the main comparison. Antihypertensive drug class compared to placebo for hypertension in children: systolic blood pressure reduction

Antihypertensive drug class compared to placebo for hypertension in children: systolic blood pressure reduction

Patient or population: children (from 1 to 18 years of age) with hypertension from primary or secondary causes
Settings: outpatient
Intervention: antihypertensive drug class
Comparison: placebo

Outcomes

Magnitude of reduction in systolic blood pressuremmHg in treatment group minus placebo response

Mean difference with 95% CI

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Angiotensin receptor blocker (any dose)

Mean duration of 4 weeks

‐6.50 (‐9.44 to ‐3.56)

240
(1 study)

⊕⊝⊝⊝
Very low

Refer 1 , 2 , 4 and 5 below.

Beta‐blocker (any dose)
Mean duration of 4 weeks

‐4.20 (‐8.12 to ‐0.28)

140
(1 study)

⊕⊝⊝⊝

Very low

Refer 1 to 5 below.

Calcium channel blocker (any dose)
Mean duration of 3 weeks

‐0.62 (‐2.97 to 1.73)

133
(1 study)

⊕⊝⊝⊝
Very low

Refer 1 to 5 below.

Beta‐blocker/thiazide combination (any dose)

Mean duration of 10 weeks

‐4.40 (‐8.99 to 0.19)

94
(1 study)

⊕⊝⊝⊝
Very low

Refer 1 to 5 below.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Comments:

1. Evidence based on only one study.

2. “Industry‐funded study. Industry‐funded studies are at risk of over‐estimating effect size.”

3. “Wide confidence interval.”

4. “High risk of publication bias.”

5. “Unclear method of randomisation and allocation concealment”.
Figuras y tablas -
Summary of findings for the main comparison. Antihypertensive drug class compared to placebo for hypertension in children: systolic blood pressure reduction
Ir a la tabla de la revisión
Summary of findings 2. Antihypertensive drug class compared to placebo for hypertension in children: diastolic blood pressure reduction

Antihypertensive drug class compared to placebo for hypertension in children: diastolic blood pressure reduction

Patient or population: children (from 1 to 18 years of age) with hypertension from primary or secondary causes
Settings: outpatient
Intervention: antihypertensive drug class
Comparison: placebo

Outcomes

Magnitude of reduction in diastolic blood pressure mmHg in treatment group minus placebo response

Mean difference with 95% CI

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Angiotensin receptor blocker (any dose)

Mean duration of 4 weeks

‐5.50 (‐9.62 to ‐1.38)

240
(1 study)

⊕⊝⊝⊝
Very low

Refer to 1, 2, 4 and 5 below.

Beta‐blocker (any dose)
Mean duration of 4 weeks

‐3.20 (‐7.12 to 0.72)

140
(1 study)

⊕⊝⊝⊝
Very low

Refer to 1 to 5 below.

Calcium channel blocker (any dose)
Mean duration of 3 weeks

‐1.86 (‐5.23 to 1.51)

133
(1 study)

⊕⊝⊝⊝
Very low

Refer to 1 to 5 below.

Beta‐blocker/thiazide combination (any dose)

Mean duration of 10 weeks

‐4.5 (‐8.26 to ‐0.74)

94
(1 study)

⊕⊝⊝⊝
Very low

Refer to 1 to 5 below.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Comments:

1. Evidence based on only one study.

2. “Industry‐funded study. Industry‐funded studies are at risk of over‐estimating effect size.”

3. “Wide confidence interval.”

4. “High risk of publication bias.”

5. “Unclear method of randomisation and allocation concealment”.
Figuras y tablas -
Summary of findings 2. Antihypertensive drug class compared to placebo for hypertension in children: diastolic blood pressure reduction
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Summary of findings 3. Angiotensin receptor blocker for hypertension in children: dose response in systolic blood pressure

Angiotensin receptor blocker for hypertension in children: dose response in systolic blood pressure

Patient or population: children (from 1 to 18 years of age) with hypertension from primary or secondary causes
Settings: outpatient
Intervention: angiotensin receptor blocker at a particular dose
Comparison: angiotensin receptor blocker at a different dose

Outcomes

Magnitude of reduction in systolic blood pressure mmHg in treatment group at various dose comparisons

Mean difference with 95% CI

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Angiotensin receptor blocker >/= 6 years

Angiotensin receptor blocker (high‐ versus low‐dose)

‐4.16 (‐5.47 to ‐2.86)

418 (5 studies)

⊕⊕⊝⊝
Low

Refer to 1 and 3 below.

Angiotensin receptor blocker (high‐ versus medium‐dose)

‐0.46 (‐2.44 to 1.53)

237 (3 studies)

⊕⊝⊝⊝
Very Low

Refer to 1 to 3 below.

Angiotensin receptor blocker (medium‐ versus low‐dose)

‐3.13 (‐5.43 to ‐0.83)

160 (3 studies)

⊕⊝⊝⊝
Very Low

Refer to 1 and 3 below.

Angiotensin receptor blocker < 6 years

Angiotensin receptor blocker (high‐ versus low‐dose)

‐3.01 (‐8.79 to 2.76)

67 (2 studies)

⊕⊝⊝⊝

Very Low

Refer to 1 to 3 below.

Angiotensin receptor blocker (high‐ versus medium‐dose)

‐1.76 (‐4.80 to 1.29)

67 (2 studies)

⊕⊝⊝⊝

Very Low

Refer to 1 to 3 below.

Angiotensin receptor blocker (medium‐ versus low‐dose)

‐1.32 (‐4.54 to 1.90)

50 (2 studies)

⊕⊝⊝⊝

Very Low

Refer to 1 to 3 below.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Comments:

1. “Industry‐funded study. Industry‐funded studies are at risk of over‐estimating effect size.”

2. “Wide confidence interval.”

3. “Unclear method of randomisation and allocation concealment in some studies”.
Figuras y tablas -
Summary of findings 3. Angiotensin receptor blocker for hypertension in children: dose response in systolic blood pressure
Ir a la tabla de la revisión
Summary of findings 4. Angiotensin receptor blocker for hypertension in children: dose response in diastolic blood pressure

Angiotensin receptor blocker for hypertension in children: dose response in diastolic blood pressure

Patient or population: children (from 1 to 18 years of age) with hypertension from primary or secondary causes
Settings: outpatient
Intervention: angiotensin receptor blocker at a particular dose
Comparison: angiotensin receptor blocker at a different dose

Outcomes

Magnitude of reduction in diastolic blood pressuremmHg in treatment group at various dose comparisons

Mean difference with 95% CI

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Angiotensin receptor blocker >/= 6 years

High‐ versus low‐dose

‐3.48 (‐5.00 to ‐1.95)

418 (5 studies)

⊕⊕⊝⊝
Low

Evidence based on 5 reasonable quality studies.

Refer to comments 1 and 3.

High‐ versus medium‐dose

‐0.59 (‐2.49 to 1.32)

237 (3 studies)

⊕⊝⊝⊝
Very low

Refer to comments 1 to 3.

Medium‐ versus low‐dose

‐3.04 (‐5.67to ‐0.40)

160 (3 studies)

⊕⊝⊝⊝
Very low

Refer to comments 1 and 3.

Angiotensin receptor blocker < 6 years

High‐ versus low‐dose

‐2.85 (‐8.63 to 2.92)

67 (2 studies)

⊕⊝⊝⊝

Very low

Refer to comments 1 to 3.

High‐ versus medium‐dose

‐0.56 (‐4.42 to 3.29)

67 (2 studies)

⊕⊝⊝⊝

Very low

Refer to comments 1 to 3.

Medium‐ versus low‐dose

‐1.31 (‐3.74 to 1.12)

50 (2 studies)

⊕⊝⊝⊝

Very low

Refer to comments 1 to 3.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Comments:

1. “Industry‐funded study. Industry‐funded studies are at risk of over‐estimating effect size.”

2. “Wide confidence interval.”

3. “Unclear method of randomisation and allocation concealment in some studies”.
Figuras y tablas -
Summary of findings 4. Angiotensin receptor blocker for hypertension in children: dose response in diastolic blood pressure
Ir a la tabla de la revisión
Summary of findings 5. Angiotensin converting enzyme inhibitor for hypertension in children: dose response in systolic blood pressure

Angiotensin converting enzyme inhibitor for hypertension in children: dose response in systolic blood pressure

Patient or population: children (from 1 to 18 years of age) with hypertension from primary or secondary causes
Settings: outpatient
Intervention: angiotensin‐converting enzyme inhibitor at a particular dose
Comparison: angiotensin‐converting enzyme inhibitor at a different dose

Outcomes

Magnitude of reduction in systolic blood pressure mmHg in treatment group at various dose comparisons

Mean difference with 95% CI

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Angiotensin‐converting enzyme inhibitor

High‐ versus low‐dose

‐5.20 (‐10.46 to 0.06)

187 (3 studies)

⊕⊝⊝⊝

Very Low

Refer to 1 to 3 below.

High‐ versus medium‐ dose

‐2.72 (‐5.83 to 0.40)

187 (3 studies)

⊕⊝⊝⊝

Very Low

Refer to 1 to 3 below.

Medium‐ versus low‐dose

‐2.01 (‐6.07 to 2.05)

139 (3 studies)

⊕⊝⊝⊝

Very Low

Refer to 1 to 3 below.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Comments:

1. “Industry‐funded study. Industry‐funded studies are at risk of over‐estimating effect size.”

2. “Wide confidence interval.”

3. “Unclear method of randomisation and allocation concealment in some studies”.
Figuras y tablas -
Summary of findings 5. Angiotensin converting enzyme inhibitor for hypertension in children: dose response in systolic blood pressure
Ir a la tabla de la revisión
Summary of findings 6. Angiotensin converting enzyme inhibitor for hypertension in children: dose response in diastolic blood pressure

Angiotensin converting enzyme inhibitor for hypertension in children: dose response in diastolic blood pressure

Patient or population: children (from 1 to 18 years of age) with hypertension from primary or secondary causes
Settings: outpatient
Intervention: angiotensin‐converting enzyme inhibitor at a particular dose
Comparison: angiotensin‐converting enzyme inhibitor at a different dose

Outcomes

Magnitude of reduction in diastolic blood pressuremmHg in treatment group at various dose comparisons

Mean difference with 95% CI

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

High‐ versus low‐dose

‐5.81 (‐11.87 to 0.26)

187 (3 studies)

⊕⊝⊝⊝

Very Low

Refer comments 1 to 3.

High‐ versus medium‐dose

‐4.31 (‐8.59 to ‐0.03)

187 (3 studies)

⊕⊝⊝⊝

Very Low

Refer comments 1 to 3.

Medium‐ versus low‐dose

‐0.46 (‐2.19 to 1.27)

139 (3 studies)

⊕⊝⊝⊝

Very Low

Refer comments 1 to 3.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Comments:

1. “Industry‐funded study. Industry‐funded studies are at risk of over‐estimating effect size.”

2. “Wide confidence interval.”

3. “Unclear method of randomisation and allocation concealment in some studies”.
Figuras y tablas -
Summary of findings 6. Angiotensin converting enzyme inhibitor for hypertension in children: dose response in diastolic blood pressure
Ir a la tabla de la revisión
Summary of findings 7. Calcium channel blocker for hypertension in children: dose response in systolic and diastolic blood pressure

Calcium channel blocker for hypertension in children: dose response in systolic and diastolic blood pressure

Patient or population: children (from 1 to 18 years of age) with hypertension from primary or secondary causes
Settings: outpatient
Intervention: calcium channel blocker at a particular dose
Comparison: calcium channel blocker at a different dose

Outcomes

Magnitude of reduction in systolic blood pressure mmHg in treatment group at various dose comparisons

Mean difference with 95% CI

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

High vs low dose

Systolic blood pressure

‐1.7 (‐4.43 to 1.03)

141 (1 study)

⊕⊝⊝⊝

Very Low

Refer to 1 to 5 below.

High vs low dose

Diastolic blood pressure

‐0.70 (‐2.63 to 1.29)

141 (1 study)

⊕⊝⊝⊝

Very Low

Refer comments from 1 to 5.

Only 2 doses were studied. Dose was not based on child's weight.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Comments:

1. Evidence based on only one study.

2. “Industry‐funded study. Industry‐funded studies are at risk of over‐estimating effect size.”

3. “Wide confidence interval.”

4. “High risk of publication bias.”

5. “Unclear method of randomisation and allocation concealment”.
Figuras y tablas -
Summary of findings 7. Calcium channel blocker for hypertension in children: dose response in systolic and diastolic blood pressure
Ir a la tabla de la revisión
Table 1. Effect on systolic and diastolic blood pressure in paediatric trials of antihypertensive agents versus placebo

Study

n

Systolic blood pressure:
mean change from baseline

SD

95% CI

Diastolic blood pressure:
mean change from baseline

SD

95% CI

Angiotensin receptor blocker

Trachtman 2008 (candesartan)

Low (0.05 mg/kg)

69

‐8.50

8.00

‐10.39 to ‐6.61

‐5.30

9.1

‐7.45 to ‐3.15

Medium (0.2 mg/kg)

68

‐10.80

9.60

‐13.08 to ‐8.52

‐7.60

10.2

‐10.02 to ‐5.18

High (0.4 mg/kg)

68

‐11.30

10.80

‐13.87 to ‐8.73

‐7.00

9.9

‐9.35 to ‐4.65

Placebo

35

‐3.80

7.80

‐6.38 to ‐1.22

‐1.30

11.5

‐5.11 to 2.51

Wells 2010 (telmisartan)

Low (1 mg/kg)

28

‐9.00

7.80

‐6.10 to ‐11.90

‐7.70

9.60

‐4.10 to ‐11.30

High (2 mg/kg)

31

‐13.00

8.70

‐9.90 to ‐16.10

‐7.80

8.10

‐4.90 to ‐10.70

Placebo

14

‐4.70

10.70

+0.90 to ‐10.30

‐2.90

7.60

+1.10 to ‐6.90

Beta‐blocker

Batisky 2007 (metoprolol)

Low (0.2 mg/kg)

45

‐5.20

8.70

‐7.70 to ‐2.60

‐3.10

8.90

‐5.70 to ‐0.50

Medium (1 mg/kg)

23

‐7.70

8.60

‐11.30 to ‐4.00

‐4.90

8.90

‐8.60 to ‐1.30

High (2 mg/kg)

49

‐6.30

9.00

‐8.70 to ‐3.80

‐7.50

8.90

‐10.00 to ‐5.00

Placebo

23

‐1.90

8.90

‐5.50 to 1.80

‐2.10

8.80

‐5.70 to 1.50

Combination

Sorof 2002 (bisoprolol/hydrochlorothiazide)

Bisoprolol 10 mg/hydrochlorothiazide 6.25 mg

62

‐9.30

11.81

‐12.24 to ‐6.36

‐7.20

9.45

‐9.55 to ‐4.85

Placebo

32

‐4.90

10.18

‐8.43 to ‐1.37

‐2.70

8.49

‐5.64 to 0.24

Calcium channel blocker

Trachtman 2003 (felodipine extended‐release)

Placebo corrected

Placebo corrected

Low (2.5 mg)

33

‐0.71

11.99

‐4.80 to 3.38

‐2.07

13.94

‐6.82 to 2.69

Medium (5 mg)

34

‐0.06

11.80

‐4.60 to 3.33

‐4.64

13.79

‐9.18 to 0.09

High (10 mg)

31

‐1.13

11.86

‐5.30 to 3.05

+1.31

13.73

‐3.56 to 6.11

CI: confidence interval; SD: standard deviation. All doses mentioned are: per day

Figuras y tablas -
Table 1. Effect on systolic and diastolic blood pressure in paediatric trials of antihypertensive agents versus placebo
Ir a la tabla de la revisión
Table 2. Dose response effects of angiotensin receptor blockers on systolic and diastolic blood pressure in paediatric trials stratified by age

Study

n

Systolic blood pressure:
mean change from baseline

SD

95% CI

Diastolic blood pressure:
mean change from baseline

SD

95% CI

≥ 6 years of age

Shahinfar 2005 (losartan)

Low (0.07 mg/kg)

70

‐4.40

7.60

‐6.20 to ‐2.60

‐6.00

7.60

‐7.80 to ‐4.20

Medium (0.75 mg/kg)

40

‐10.00

9.10

‐12.90 to ‐7.10

‐11.70

9.10

‐14.60 to ‐8.80

High (1.44 mg/kg)

64

‐8.60

9.50

‐11.00 to ‐6.30

‐12.20

8.90

‐14.40 to ‐10.00

Wells 2011 (valsartan)

Low (0.4 mg/kg)

102

‐7.90

10.40

‐9.92 to ‐5.88

‐4.60

11.00

‐6.72 to ‐2.48

Medium (1.3 mg/kg)

52

‐9.60

9.10

‐12.07 to ‐7.13

‐5.80

8.90

‐8.22 to ‐3.38

High (2.7 mg/kg)

105

‐11.50

11.20

‐13.64 to ‐9.36

‐7.40

9.50

‐9.22 to ‐5.58

Hazan 2010a* (olmesartan)

Low (2.5/5 mg)

95

‐7.80

9.18

‐9.66 to ‐5.94

‐5.50

8.06

‐7.15 to ‐3.89

High (20/40 mg)

95

‐12.60

10.15

‐14.65 to ‐10.55

‐9.50

9.76

‐11.47 to ‐7.53

Hazan 2010b* (olmesartan)

Low (2.5/5 mg)

56

‐4.70

11.48

‐7.71 to ‐1.69

‐3.50

8.84

‐1.18 to ‐5.82

High (20/40 mg)

56

‐10.70

9.26

‐13.13 to ‐8.27

‐7.60

8.17

‐5.46 to ‐9.74

BMS 2005 (irbesartan)

Low (0.5 mg/kg)

106

‐11.7

‐

‐

‐3.80

‐

‐

Medium (1.5 mg/kg)

106

‐9.30

‐

‐

‐3.20

‐

‐

High (4.5 mg/kg)

106

‐13.30

‐

‐

‐6.60

‐

‐

< 6 years of age

Schaefer 2010 (candesartan)

Low (0.05 mg/kg)

29

‐6.00

9.40

‐9.42 to ‐2.58

‐5.20

6.70

‐7.64 to ‐2.76

Medium (0.2 mg/kg)

32

‐8.90

9.20

‐12.09 to ‐5.71

‐7.90

12.90

‐12.37 to ‐3.43

High (0.4 mg/kg)

32

‐12.10

8.30

‐14.98 to ‐9.22

‐11.10

9.20

‐14.29 to ‐7.91

Flynn 2008 (valsartan)

Low (5/10 mg)

37

‐8.40

8.44

‐11.12 to ‐5.68

‐5.50

6.06

‐7.45 to ‐3.55

Medium (20/40 mg)

18

‐8.30

7.63

‐11.82 to ‐4.78

‐6.40

4.23

‐8.35 to ‐4.45

High (40/80 mg)

35

‐8.60

7.55

‐11.10 to ‐6.10

‐5.50

8.47

‐8.31 to ‐2.69

Webb 2013 (losartan)

Low (0.1 mg/kg)

33

‐7.30

‐

‐

‐8.20

‐

‐

Medium (0.3 mg/kg)

34

‐7.60

‐

‐

‐5.10

‐

‐

High (0.7 mg/kg)

32

‐6.70

‐

‐

‐6.70

‐

‐

*Hazan 2010 study stratified study population into 2 cohorts (cohort A, 62% white; cohort B, 100% black). Cohort A was termed Hazan 2010a and Cohort B was termed Hazan 2010b. All doses mentioned are per day. CI: confidence interval; SD: standard deviation

Figuras y tablas -
Table 2. Dose response effects of angiotensin receptor blockers on systolic and diastolic blood pressure in paediatric trials stratified by age
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Table 3. Dose response effect of other antihypertensive drugs on systolic and diastolic blood pressure in paediatric trials

Study

n

Systolic blood pressure:
mean change from baseline

SD

95% CI

Diastolic blood pressure:
mean change from baseline

SD

95% CI

Angiotensin‐converting enzyme inhibitors

Wells 2002 (enalapril)

Low (0.02 mg/kg)

30

‐7.10

9.30

‐10.60 to ‐3.60

‐6.30

7.80

‐9.20 to ‐3.40

Medium (0.08 mg/kg)

29

‐6.60

10.10

‐10.40 to ‐2.80

‐8.90

8.70

‐12.20 to ‐5.60

High (0.58 mg/kg)

50

‐12.50

11.70

‐15.80 to ‐9.20

‐14.90

8.70

‐17.40 to ‐12.40

Li 2004 (fosinopril)

Low (0.1 mg/kg)

73

‐10.90

10.25

‐13.20 to ‐8.60

‐4.50

6.84

‐6.00 to ‐3.00

Medium (0.3 mg/kg)

86

‐11.30

10.25

‐13.40 to ‐9.10

‐4.20

6.49

‐5.70 to ‐2.80

High (0.6 mg/kg)

79

‐11.90

9.78

‐14.20 to ‐9.70

‐5.10

7.11

‐6.60 to ‐3.60

Soffer 2003 (lisinopril)

Low (0.02 mg/kg)

33

‐5.40

9.90

‐9.00 to ‐1.90

‐7.60

9.30

‐10.90 to ‐4.30

Medium (0.07 mg/kg)

24

‐12.10

9.10

‐16.00 to ‐8.30

‐9.30

8.70

‐13.00 to ‐5.70

High (0.61 mg/kg)

58

‐15.20

12.10

‐18.40 to ‐12.00

‐16.40

11.70

‐19.50 to 13.30

Selective aldosterone receptor blocker

Li 2011 (eplerenone)

Low (25 mg)

58

‐7.66

‐

‐

‐3.80

‐

‐

Medium (50 mg)

62

‐7.84

‐

‐

‐2.70

‐

‐

High (100 mg)

184

‐7.99

‐

‐

‐3.05

‐

‐

Calcium channel blocker

Flynn 2004 (amlodipine)

Low (2.5 mg)

127

‐7.3

11.4

‐9.3 to ‐5.3

‐3.7

8.3

‐5.1 to ‐2.3

High (5 mg)

141

‐9.0

11.4

‐10.9 to ‐7.1

‐4.4

8.3

‐5.8 to ‐3.0

*Angiotensin receptor blocker versus angiotensin‐converting enzyme inhibitor

Schaefer 2011

Valsartan (80/160/320 mg)

148

‐15.40

‐

‐

‐9.40

‐

‐

Enalapril (10/20/40 mg)

148

‐14.10

‐

‐

‐8.50

‐

‐

Calcium channel blockers versus angiotensin receptor blockers

Webb 2010 (amlodipine versuslosartan)

Amlodipine (0.05 to 0.2 mg/kg)

30

‐0.10

‐

‐

‐0.80

‐

‐

Losartan (0.7 to 1.4mg/kg)

30

‐5.50

‐

‐

‐3.40

‐

‐

Gartenmann 2003 (amlodipine versusirbesartan)

Median change from baseline

Range

Median change from baseline

Range

Amlodipine (20 to 40 kg: 5 to 10 mg; > 40 kg: 10 to 20 mg)

11

12.00

10.00 to 14.00

7.00

5.00 to 10.00

Irbesartan (20 to 40 kg: 75 to 150 mg; > 40 kg: 150 to 300 mg)

13

13.00

9 to 16

9.00

7.00 to 11.00

Alpha blocker versus diuretic, Falkner 1981 (clonidine versus hydrochlorothiazide)

Clonidine

Mean BP

SD

Mean BP

SD

Pre

15

146

16.00

138 to 154

96

6.00

93 to 99

Low (0.1 mg twice)

136

13.00

129 to 143

89

8.00

85 to 93

High (0.2 mg twice)

136

8.00

132 to 140

88

5.00

85 to 91

Hydrochlorothiazide

Pre

15

145

6.00

142 to 148

97

8.00

93 to 101

Low (25 mg twice)

139

10.00

134 to 144

94

6.00

91 to 97

High (50 mg twice)

135

11.00

129 to 141

93

8.00

89 to 97

All doses mentioned are per day

BP: blood pressure; CI: confidence interval; SD: standard deviation
Figuras y tablas -
Table 3. Dose response effect of other antihypertensive drugs on systolic and diastolic blood pressure in paediatric trials
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Table 4. Adverse effects of antihypertensive medications

Drugs

Common side effects

Less common side effects

Angiotensin‐converting enzyme inhibitor

Headache (20.1%), nasopharyngitis (9.6%), cough (9.1%) with fosinopril
Headache (3.4%), cough (< 1%) with lisinopril. 2 in high‐dose lisinopril group had abdominal pain, diarrhoea, nausea and vomiting and 2 in medium‐dose group experienced dizziness. Only 1 event of cough was reported in the lisinopril study and thought to be unrelated to the drug

Dizziness was the most common side effect in the enalapril study (4 patients, followed by cough (3 patients) and headache (2 patients). No angioedema reported in any of the 3 trials

Low‐dose lisinopril ‐ 1 patient developed leucopenia and another patient had elevated creatinine. High‐dose lisinopril: 1 patient developed hyperkalaemia and another had elevated creatinine

In the fosinopril study: elevated creatinine was the most frequent lab abnormality (drug versus placebo 8.9% versus 4.1%). All elevations were transient and did not exceed the upper limit of normal

None of the patients in the enalapril study experienced renal failure or hyperkalaemia 

Angiotensin receptor blocker in > 6 years

Headache was reported in 33.2% of children in the valsartan study and in 5.4% to 14.7% of children in the olmesartan study

The most common side effects in the candesartan trial were headache, upper respiratory infection, dizziness, cough and sore throat

The olmesartan study reported headache (7.4%) and pharyngo‐laryngeal pain (6.3%) in the low‐dose group and headache (14.7%) and dizziness (9.5%) in the high‐dose group among the mixed racial cohort. Among the black patients, headache (5.4%) in the low‐dose and headache (8.9%) and toothache (3.6%) in high‐dose group were reported

In the valsartan study, 10% of patients had elevated creatinine and 4% patients had hyperkalaemia at some point during the study

In the candesartan trial, 8 patients discontinued treatment. The reasons for discontinuation were hypotension, arm fracture, dizziness, headache, low white cell count and progression of underlying renal disease (2 patients)

2 patients in the mixed racial group in the olmesartan study discontinued treatment (1 patient because of hypertension and other due to hypoaesthesia)

Angiotensin receptor blocker < 6 years

Angiotensin receptor blocker was well tolerated in this age group with a low incidence of side effects and no adverse effect on growth

2 significant adverse events were reported in the candesartan study (Schaefer 2010). 1 event was a death related to acute on chronic renal failure provoked by diarrhoea‐induced hypovolaemia and the second event was a vaso‐occlusive event which occurred in a child with nephrotic syndrome. The authors report that both events were not directly attributed to angiotensin receptor blocker use

1 participant each had pruritus and rash, decreased appetite and blurred vision in phase 1 of the valsartan study. In phase 2, 1 patient had headache and 1 hypertriglyceridaemia

Beta‐blocker

Headache (30%), upper respiratory infection (10%) and cough (19%) in the metoprolol study

Fatigue (9%) and dizziness (6%). 5 patients discontinued the metoprolol study in the open‐label period because of an adverse event (1 patient each for fatigue, nightmares, anxiety, dizziness and asthma)

Beta‐blocker + diuretic

No significant adverse effects reported

 

Calcium channel blocker

Headache (33%), respiratory infection (12%) and nausea (10%) were the common adverse events among children on extended‐release felodipine

Pedal oedema was noted in 2% of patients in the felodipine study and in ˜3.1% to 4.3% patients on amlodipine

Centrally acting α blocker versus diuretic

14 of the 15 hydrochlorothiazide‐treated participants had a reduction in serum potassium. Symptomatic hypokalaemia in 4 participants requiring potassium supplementation in the hydrochlorothiazide group

Drowsiness and dry mouth in 1 patient on clonidine
Figuras y tablas -
Table 4. Adverse effects of antihypertensive medications
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Comparison 1. Antihypertensive drug class versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Systolic blood pressure Show forest plot

5

Mean Difference (Random, 95% CI)

Totals not selected

1.1 ARB (any dose)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.2 ARB (high‐dose versus placebo)

2

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.3 ARB (medium‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.4 ARB (low‐dose versus placebo)

2

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.5 BB (any dose)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.6 BB (high‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.7 BB (medium‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.8 BB (low‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.9 CCB (any dose)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.10 CCB (high‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.11 CCB (medium‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.12 CCB (low‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

1.13 BB/thiazide combination (any dose) versus placebo

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2 Diastolic blood pressure Show forest plot

5

Mean Difference (Random, 95% CI)

Totals not selected

2.1 ARB (any dose)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.2 ARB (high‐dose versus placebo)

2

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.3 ARB (medium‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.4 ARB (low‐dose versus placebo)

2

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.5 BB (any dose)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.6 BB (high‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.7 BB (medium‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.8 BB (low‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.9 CCB (any dose)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.10 CCB (high‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.11 CCB (medium‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.12 CCB (low‐dose versus placebo)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]

2.13 BB/thiazide diuretic (any dose)

1

Mean Difference (Random, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 1. Antihypertensive drug class versus placebo
Ir a la tabla de la revisión
Comparison 2. Antihypertensive drug dose response

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Systolic blood pressure Show forest plot

12

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.1 ARB (high‐ versus low‐dose), age ≥ 6 years

6

837

Mean Difference (IV, Random, 95% CI)

‐4.16 [‐5.47, ‐2.86]

1.2 ARB (high‐ versus medium‐dose), age ≥ 6 years

3

397

Mean Difference (IV, Random, 95% CI)

‐0.46 [‐2.44, 1.53]

1.3 ARB (medium‐ versus low‐dose), age ≥ 6 years

3

401

Mean Difference (IV, Random, 95% CI)

‐3.13 [‐5.43, ‐0.83]

1.4 ARB (high‐ versus low‐dose), age < 6 years

2

133

Mean Difference (IV, Random, 95% CI)

‐3.01 [‐8.79, 2.76]

1.5 ARB (high‐ versus medium‐dose), age < 6 years

2

117

Mean Difference (IV, Random, 95% CI)

‐1.76 [‐4.80, 1.29]

1.6 ARB (medium‐ versus low‐dose), age < 6 years

2

116

Mean Difference (IV, Random, 95% CI)

‐1.32 [‐4.54, 1.90]

1.7 ACEI (high‐ versus low‐dose)

3

323

Mean Difference (IV, Random, 95% CI)

‐5.20 [‐10.46, 0.06]

1.8 ACEI (high‐ versus medium‐dose)

3

326

Mean Difference (IV, Random, 95% CI)

‐2.72 [‐5.83, 0.40]

1.9 ACEI (medium‐ versus low‐dose)

3

275

Mean Difference (IV, Random, 95% CI)

‐2.01 [‐6.07, 2.05]

1.10 CCB (high‐ versus low‐dose)

1

268

Mean Difference (IV, Random, 95% CI)

‐1.70 [‐4.43, 1.03]

2 Diastolic blood pressure Show forest plot

12

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.1 ARB (high‐ versus low‐dose), age ≥ 6 years

6

837

Mean Difference (IV, Random, 95% CI)

‐3.48 [‐5.00, ‐1.95]

2.2 ARB (high‐ versus medium‐dose), age ≥ 6 years

3

397

Mean Difference (IV, Random, 95% CI)

‐0.59 [‐2.49, 1.32]

2.3 ARB (medium‐ versus low‐dose), age ≥ 6 years

3

401

Mean Difference (IV, Random, 95% CI)

‐3.04 [‐5.67, ‐0.40]

2.4 ARB (high‐ versus low‐dose), age < 6 years

2

133

Mean Difference (IV, Random, 95% CI)

‐2.85 [‐8.63, 2.92]

2.5 ARB (high‐ versus medium‐dose), age < 6 years

2

117

Mean Difference (IV, Random, 95% CI)

‐0.56 [‐4.42, 3.29]

2.6 ARB (medium‐ versus low‐dose), age < 6 years

2

116

Mean Difference (IV, Random, 95% CI)

‐1.31 [‐3.74, 1.12]

2.7 ACEI (high‐ versus low‐dose)

3

323

Mean Difference (IV, Random, 95% CI)

‐5.81 [‐11.87, 0.26]

2.8 ACEI (high‐ versus medium‐dose)

3

326

Mean Difference (IV, Random, 95% CI)

‐4.31 [‐8.59, ‐0.03]

2.9 ACEI (medium‐ versus low‐dose)

3

275

Mean Difference (IV, Random, 95% CI)

‐0.46 [‐2.19, 1.27]

2.10 CCB (high‐ versus low‐dose)

1

268

Mean Difference (IV, Random, 95% CI)

‐0.70 [‐2.69, 1.29]
Figuras y tablas -
Comparison 2. Antihypertensive drug dose response
Ir a la tabla de la revisión