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Cochrane Database of Systematic Reviews

Statins for aortic valve stenosis

Information

DOI:
https://doi.org/10.1002/14651858.CD009571.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 05 September 2016see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:

  1. Cochrane Heart Group

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Luciana Thiago

    Department of Education in Health Sciences, Marilia Medical School, Marilia, Brazil

  • Selma Rumiko Tsuji

    Department of Psychiatry and Evidence Based Health Actions, Marilia Medical School, Marilia, Brazil

  • Jonathan Nyong

    Institute of Health Informatics, University College London, London, UK

  • Maria ES Puga

    Brazilian Cochrane Centre, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, Brazil

  • Aecio FT Gois

    Correspondence to: Brazilian Cochrane Centre, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

    [email protected]

    [email protected]

  • Cristiane R Macedo

    Brazilian Cochrane Centre, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, Brazil

  • Orsine Valente

    Brazilian Cochrane Centre, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, Brazil

  • Álvaro N Atallah

    Brazilian Cochrane Centre, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, Brazil

Contributions of authors

Luciana Thiago: is the primary author of the review, drafted the protocol, searched the references, entered data into RevMan, selected the included papers, extracted the data, organised and analysed data and drafted the manuscript.

Selma Rumiko Tsuji: Drafted the protocol.

Jonathan Nyong: Quality assured the report and data entry, organised the data into GRADE software and produced 'Summary of findings' table

Maria Eduarda dos Santos Puga: Developed the search strategy.

Aécio Flávio Teixeira de Góis: Extracted and analysed the data.

Cristiane Rufino Macedo: Entered the data into Revman and organised the data into GRADE software.

Orsine Valente: Drafted the protocol.

Álvaro Nagib Átallah: Organised and analysed the data.

Sources of support

Internal sources

  • Brazilian Cochrane Centre, Federal University of Sao Paulo and Marilia Medical, Brazil.

External sources

  • No sources of support supplied

Declarations of interest

There is no conflict of interest in this review.

Acknowledgements

We thank the staff of the Cochrane Heart Group for their help and assistance with the systematic review. We also thank Dr Álvaro Nagib Atallah (Director) and the staff of the Brazilian Cochrane Centre for their orientation and assistance with the review. We thank Patricia Moerbeck Casadei for her assistance with the English version of this study. We are grateful to Nicole Martin and Jo Abbot for conducting the searches for this review.

Version history

Published

Title

Stage

Authors

Version

2016 Sep 05

Statins for aortic valve stenosis

Review

Luciana Thiago, Selma Rumiko Tsuji, Jonathan Nyong, Maria ES Puga, Aecio FT Gois, Cristiane R Macedo, Orsine Valente, Álvaro N Atallah

https://doi.org/10.1002/14651858.CD009571.pub2

2012 Jan 18

Statins for aortic valve stenosis

Protocol

Luciana Thiago, Selma Rumiko Tsuji, Álvaro N Atallah, Maria Eduarda dos Santos Puga, Aecio FT Gois, Orsine Valente

https://doi.org/10.1002/14651858.CD009571

Differences between protocol and review

We included GRADE to assess the quality evidence of the review (GRADE PRO 2011).

Two new co‐authors were added (Cristiane Rufino Macedo and Jonathan Nyong).

We excluded two studies on the basis of high risk of bias and methodological flaws as instructed by the editorial staff. The low number of patients in these trials suggests that no significant change could occur in meta‐analysis results.

In the protocol of this review, we planned to assess if the effect of the treatment varies according to different populations (age, gender and severity of illness) or to characteristics of the intervention (type of statin). However, the numbers of the included studies identified by the electronic search were not enough to carry out subgroup analysis. We also did not conduct the planned sensitivity analysis to assess the robustness of the observed effects due to insufficient number of trials. Although we did not specify the number in the protocol, we consider that at least 10 included studies are required to carry out subgroup and sensitivity analyses. In future updates of this review, we intend to carry out subgroup analysis by age, gender, type of statin and severity of Illness (mild, moderate and severe aortic valve stenosis) and sensitivity analysis, provided we have more than 10 eligible studies.

We planned to calculate NNT (number needed to treat for an additional beneficial outcome (NNTB) or the number needed to treat for an additional harmful outcome (NNTH)) (Higgins 2011) in the protocol, but it was not possible because we did not find any significant difference between the participants who received statin compared with the participants who received placebo for the following outcomes: mean pressure gradient, freedom from valve replacement, death from cardiovascular cause and valve area.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

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'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias 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.
Figures and Tables -
Figure 3

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

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Comparison 1 Statin versus Placebo, Outcome 1 Mean pressure gradient.
Figures and Tables -
Analysis 1.1

Comparison 1 Statin versus Placebo, Outcome 1 Mean pressure gradient.

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Comparison 1 Statin versus Placebo, Outcome 2 Valve area.
Figures and Tables -
Analysis 1.2

Comparison 1 Statin versus Placebo, Outcome 2 Valve area.

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Comparison 1 Statin versus Placebo, Outcome 3 Aortic jet velocity.
Figures and Tables -
Analysis 1.3

Comparison 1 Statin versus Placebo, Outcome 3 Aortic jet velocity.

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Comparison 1 Statin versus Placebo, Outcome 4 Freedom from valve replacement.
Figures and Tables -
Analysis 1.4

Comparison 1 Statin versus Placebo, Outcome 4 Freedom from valve replacement.

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Comparison 1 Statin versus Placebo, Outcome 5 Death from cardiovascular cause.
Figures and Tables -
Analysis 1.5

Comparison 1 Statin versus Placebo, Outcome 5 Death from cardiovascular cause.

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Comparison 1 Statin versus Placebo, Outcome 6 Hospitalisation for any reason.
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Analysis 1.6

Comparison 1 Statin versus Placebo, Outcome 6 Hospitalisation for any reason.

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Comparison 1 Statin versus Placebo, Outcome 7 Severe adverse events.
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Analysis 1.7

Comparison 1 Statin versus Placebo, Outcome 7 Severe adverse events.

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Summary of findings for the main comparison. Statin versus Placebo for aortic valve stenosis

Statin versus Placebo for aortic valve stenosis

Patient or population: patients with aortic valve stenosis
Settings: Outpatients and hospitalisation
Intervention: Statin versus Placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Assumed risk

Corresponding risk

Placebo

Statin

Mean pressure gradient (mmHg)

Better indicated by lower scores.

Follow‐up: median 2.4 to 4.5 years

The mean mean pressure gradient in the control groups was
34 to 35 mmHg

The mean mean pressure gradient in the intervention groups was
0.54 lower
(1.88 lower to 0.8 higher)

MD ‐0.54 (‐1.88 to 0.80)

1935
(2 studies)

⊕⊕⊝⊝
low1,2

Valve area (cm2)
Better indicated by higher scores.

Follow‐up: median 2.4‐ to 3.5 years

The mean valve area in the control groups was
1 to 1.5 cm2

The mean valve area in the intervention groups was
0.07 lower
(0.28 lower to 0.14 higher)

MD ‐0.07 (‐0.28 to 0.14)

127
(2 studies)

⊕⊕⊝⊝
low2,3

Aortic jet velocity (m/s)
Follow‐up: median 2.1 years

The mean aortic jet velocity in the control groups was
3.45 m per second

The mean aortic jet velocity in the intervention groups was
0.06 lower
(0.26 lower to 0.14 higher)

MD ‐0.06 (‐0.26 to 0.14)

155
(1 study)

⊕⊕⊝⊝
low2, 3

Freedom from valve replacement
Follow‐up: median 2.1 to 4.5 years

Study population

RR 0.93
(0.81 to 1.06)

2360
(4 studies)

⊕⊕⊕⊝
moderate2

281 per 1000

261 per 1000
(227 to 298)

Moderate population

222 per 1000

206 per 1000
(180 to 235)

Death from cardiovascular cause
Follow‐up: median 2.1 to 4.5 years

Study population

RR 0.80
(0.56 to 1.15)

2297
(3 studies)

⊕⊕⊝⊝
low2,4

56 per 1000

45 per 1000
(31 to 64)

Moderate population

39 per 1000

31 per 1000
(22 to 45)

Hospitalisation for any reason
Follow‐up: median 2.1 years

154 per 1000

129 per 1000
(60 to 283)

RR 0.84
(0.39 to 1.84)

155
(1 study)

⊕⊝⊝⊝
very low2,3,4

Adverse events ‐ Muscle pain
Follow‐up: median 2.4 to 4.5 years

Study population

RR 0.91
(0.75 to 1.09)

2204
(3 studies)

⊕⊕⊕⊝
moderate2

168 per 1000

153 per 1000
(126 to 183)

Moderate population

30 per 1000

27 per 1000
(22 to 33)

*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; RR: Risk ratio;

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.

1 Downgraded by one due to randomisation and allocation being unclear for Rossebø 2008.
2 Downgraded by one due to possible risk of publication bias as only a small number of studies were identified.
3 Downgraded by one due to imprecision: small sample size with effect size crossing the line of no effect.
4 Downgraded by one due to imprecision: very few events < 300.

Figures and Tables -
Summary of findings for the main comparison. Statin versus Placebo for aortic valve stenosis
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Table 1. Echocardiografic criteria for aortic valve stenosis (Vahanian 2012; Nishimura 2014)

Mild

Aortic stenosis

Moderate

Aortic stenosis

Severe

Aortic stenosis

Valve area

1.5 cm²

1.0 to 1.5 cm²

< 1.0 cm²

Mean pressure

gradient

< 20 mmHg

20 to 39 mmHg

> 40 mmHg

Aortic jet velocity

< 2.0 to 2.9 m

per second

3.0 to 3.9 m

per second

> 4.0 m

per second
Figures and Tables -
Table 1. Echocardiografic criteria for aortic valve stenosis (Vahanian 2012; Nishimura 2014)
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Comparison 1. Statin versus Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mean pressure gradient Show forest plot

2

1935

Mean Difference (IV, Fixed, 95% CI)

‐0.54 [‐1.88, 0.80]

2 Valve area Show forest plot

2

127

Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.28, 0.14]

3 Aortic jet velocity Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4 Freedom from valve replacement Show forest plot

4

2360

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.81, 1.06]

5 Death from cardiovascular cause Show forest plot

3

2297

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.56, 1.15]

6 Hospitalisation for any reason Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7 Severe adverse events Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Muscle pain

3

2204

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.75, 1.09]

7.2 Hepatic enzymes elevation

2

2109

Risk Ratio (M‐H, Fixed, 95% CI)

2.66 [1.24, 5.67]

7.3 Hepatitis

2

2141

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.40, 3.25]

7.4 Gastrointestinal condition

3

2296

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.96, 1.25]

7.5 Creatine kinase

2

2109

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.17, 3.33]
Figures and Tables -
Comparison 1. Statin versus Placebo
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