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Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)
Medwave 2017; 17(Suppl1):e6853 doi: 10.5867/medwave.2017.6853
Are statins beneficial for chronic heart failure? - First update
Carmen Rain, Gabriel Rada
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Abstract

This Living FRISBEE (Living FRIendly Summary of the Body of Evidence using Epistemonikos) is an update of an article published in May 2015 (doi: 10.5867/medwave.2015.04.6140), based on the detection of nine new systematic reviews.

Even though statins decrease inflammatory markers and improve some echocardiographic parameters in heart failure, it is not clear whether they have an impact on clinically important outcomes. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified 15 systematic reviews including 25 randomized trials answering the question of interest. We extracted data, combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded statins do not decrease mortality in chronic heart failure, and might lead to a small reduction in hospital admissions for heart failure, but the certainty of this evidence is low.


 
About the update

This Living FRISBEE (Living FRIendly Summary of the Body of Evidence using Epistemonikos) is an update of the summary published in May 2015 (doi: 10.5867/medwave.2015.04.6140), based on the detection of nine new systematic reviews.

The new evidence incorporated in this summary does not lead to changes in the certainty of the evidence, the estimates of the magnitude of effects, the key messages or the considerations for decision-making.

Problem

Apart from their main effects on serum lipid levels, statins would have pleiotropic properties, such as antihypertrophic, antifibrotic, antioxidant and inhibitor of neurohumoral activation, all of them involved in the pathophysiology of heart failure. Some studies have shown statins would improve ejection fraction and decrease inflammatory biomarkers, however it is not clear if these effects translate into a clinically important benefit.

Methods

We used Epistemonikos database, which is maintained by screening multiple databases, to identify systematic reviews and their included primary studies. With this information, we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

  • Statins do not decrease mortality in chronic heart failure.
  • Statins might slightly reduce hospital admissions for heart failure, but the certainty of this evidence is low.
  • The balance between benefits and risks for the use of statins in chronic heart failure without other indication is probably not favorable.
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

We found fifteen systematic reviews [1],[2],[3],[4],[5],
[6],[7],[8],[9],[10],[11],[12],[13],[14],[15] including 45
[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],
[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],
[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],
[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62],[63]
[64] primary studies, of which 25 correspond to randomised controlled trials, reported in 29 references [17],[18],[20],[30],[31],[33],[34],[36],[40],
[41],[45],[46],[48],[49],[50],[51],[52],[53],[54],[55],
[56],[57],[58],[59],[60],[61],[62],[63],[64].

This table and the summary in general are based on the latter.

What types of patients were included

The trials included patients with heart failure from any cause receiving standard treatment. Most trials only included patients with low ejection fraction, except three trials [36],[50],[57].

Four trials included patients with NYHA functional class I
[40],[46],[48],[61], 23 functional class II [18],[31],[34],
[36],[40],[41],[45],[46],[48],[49],[50],[53],[54],[55],[56],
[57],[58],[59],[60],[61],[62],[63],[64] all of the trials included functional class III and eight included functional class IV [34],[36],[49],[53],[55],[58],[59],[63],[64].

The average LDL cholesterol level ranged from 96 to 167 mg/dL in the different trials.

What types of interventions were included

Seventeen trials evaluated atorvastatin [34],[40],[41],
[46],[48],[49],[50],[51],[52],[53],[55],[56],[60],[61],
[62],[63],[64] five rosuvastatin [18],[31],[36],[58],[59], one cerivastatin [57], one pivastatin [54] and one simvastatin [45].

Most of the trials compared against placebo, with exception of 11 trials that compared against no-intervention [34],[48],[49],[50],[51],[52],[53],[54],[61], [62],[63].

What types of outcomes
were measured

The systematic reviews reported the following outcomes:

  • Total mortality
  • Cardiovascular mortality
  • Hospitalization for heart failure
  • Myocardial infarction
  • Stroke
  • Echocardiographic parameters
  • Inflammatory biomarkers
  • B-type natriuretic peptide (BNP) levels
  • QT interval
  • NYHA functional class
Summary of findings

The information on the effects of statins is based on 25 randomized controlled trials. Seventeen trials reported mortality [36],[40],[45],[48],[49],[50],[51],[52],[54],[55],[56],[58],[59],[60],[61],[62],[63] and 14 trials reported the risk of hospitalization for heart failure [36],[45],[48],[49],[50],[52],[54],[55],[56],[58],[59],[60],[61],[62]. The summary of findings is the following:

  • Statins do not decrease mortality in chronic heart failure. The certainty of the evidence is high.
  • Statins might slightly reduce hospital admissions for heart failure, but the certainty of this evidence is low.

Other considerations for decision-making

To whom this evidence does and does not apply
  • This evidence applies to chronic heart failure of any etiology and functional class not requiring statins for other reasons.
  • It does not apply to patients with previous coronary or atherosclerotic events, which is a clear indication of statins as secondary prevention.
  • It is difficult to be certain whether some patients included in these trials should have received statins based on their cholesterol level. It is reasonable to evaluate this in a case-by-case basis, incorporating individualized cardiovascular risk.
About the outcomes included in this summary
  • The outcomes presented in this summary are those considered critical for decision-making in the main guidelines, the systematic reviews identified, and according to the opinion of the authors of this summary.
Balance between benefits and risks, and certainty of the evidence
  • Statins constitute a low-risk intervention, with mild adverse effects. However, it is difficult to balance benefits and harms because the certainty of the evidence is low for the potential benefit.
  • If the benefit were certain, it would be reasonable to favor this intervention in patients with a higher hospitalization risk that have not presented important adverse effects.
Resource considerations
  • Statins have low cost. However, it is difficult to balance cost and benefit because the certainty of the evidence is low. However, it is unlikely that this factor would determine the decision. 

Differences between this summary and other sources
  • The systematic reviews identified differ in their conclusions, and some even state there is a clear mortality benefit [11]. However, this summary is in agreement with the main guidelines addressing this question [65],[66], which conclude there is no benefit in heart failure patients. 
Could this evidence change in the future?
  • The probability that the information on the effect of statins on mortality change in the future is very low.
  • We did not identify any ongoing trial answering this question in the International Clinical Trials Registry Platform of the World Health Organization 
How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Are statins beneficial in chronic heart failure?

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

Este resumen Epistemonikos (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos) es una actualización del resumen publicado en mayo de 2015, basado en nueve revisiones sistemáticas aparecidas con posterioridad.

Si bien las estatinas disminuyen parámetros inflamatorios y mejoran algunos parámetros ecocardiográficos en pacientes con insuficiencia cardiaca, no está claro si esto se traduce en beneficios clínicamente relevantes. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos, identificamos 15 revisiones sistemáticas que en conjunto incluyen 25 estudios aleatorizados que responden la pregunta de interés. Extrajimos los datos, realizamos un metanálisis y preparamos tablas de resumen de los resultados utilizando el método GRADE. Concluimos que las estatinas no disminuyen la mortalidad en pacientes con insuficiencia cardiaca. Podrían tener un efecto pequeño sobre el riesgo de hospitalización, pero la certeza de esta evidencia es baja.

Authors: Carmen Rain[1], Gabriel Rada[1,2,3,4,5]

Affiliation:
[1] Proyecto Epistemonikos, Santiago, Chile
[2] Programa de Salud Basada en Evidencia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[3] Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[4] GRADE working group
[5] The Cochrane Collaboration

E-mail: radagabriel@epistemonikos.org

Author address:
[1] Facultad de Medicina
Pontificia Universidad Católica de Chile
Diagonal Paraguay 476
Santiago Centro
Chile

Citation: Rain C, Rada G. Are statins beneficial for chronic heart failure? - First update. Medwave 2017; 17(Suppl1):e6853 doi: 10.5867/medwave.2017.6853

Submission date: 22/12/2016

Acceptance date: 23/12/2016

Publication date: 25/4/2017

PubMed record

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Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the american college of cardiology foundation/american heart association task force on practice guidelines. Circulation. 2013;128(16):240–327

July 2022, Vol 22, Issue 6
icon Research papers
Association of biomarkers and severity of COVID-19: A crosssectional study

Systematization of initiatives in sexual and reproductive health about good practices criteria in response to the COVID-19 pandemic in primary health care in Chile

Clinical, psychological, social, and family characterization of suicidal behavior in Chilean adolescents: a multiple correspondence analysis

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