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Journal of General Internal Medicine

, Volume 34, Issue 8, pp 1607–1614 | Cite as

Postponement of Death by Statin Use: a Systematic Review and Meta-analysis of Randomized Clinical Trials

  • Morten Rix HansenEmail author
  • Asbjørn Hróbjartsson
  • Anton Pottegård
  • Per Damkier
  • Kasper Søltoft Larsen
  • Kenneth Grønkjær Madsen
  • René dePont Christensen
  • Malene Elisa Lopez Kristensen
  • Palle Mark Christensen
  • Jesper Hallas
Review Article

Abstract

Background

The average postponement of the outcome (gain in time to event) has been proposed as a measure to convey the effect of preventive medications. Among its advantages over number needed to treat and relative risk reduction is a better intuitive understanding among lay persons.

Objectives

To develop a novel approach for modeling outcome postponement achieved within a trial’s duration, based on published trial data and to present a formalized meta-analysis of modeled outcome postponement for all-cause mortality in statin trials.

Methods

The outcome postponement was modeled on the basis of the hazard ratio or relative risk, the mortality rate in the placebo group and the trial’s duration. Outcome postponement was subjected to a meta-analysis. We also estimated the average outcome postponement as the area between Kaplan–Meier curves. Statin trials were identified through a systematic review.

Results

The median modeled outcome postponement was 10.0 days (interquartile range, 2.9–19.5 days). Meta-analysis of 16 trials provided a summary estimate of outcome postponement for all-cause mortality of 12.6 days, with a 95% postponement interval (PI) of 7.1–18.0. For primary, secondary, and mixed prevention trials, respectively, outcome postponements were 10.2 days (PI, 4.0–16.3), 17.4 days (PI, 6.0–28.8), and 8.5 days (PI, 1.9–15.0).

Conclusions

The modeled outcome postponement is amenable to meta-analysis and may be a useful approach for presenting the benefits of preventive interventions. Statin treatment results in a small increase of average survival within the duration of a trial.

Systematic Review Registration

The systematic review was registered in PROSPERO [CRD42016037507].

Notes

Acknowledgments

We thank Jesper Urban Pedersen, Senior Creative, for the technical advice regarding the use of Adobe Photoshop and Manan Pareek, M.D., for reviewing the statin trial classifications.

Authors’ Contribution

All authors have made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data. They have all participated in drafting of the paper or revising it critically for important intellectual content. All authors have read and approved the final version of the manuscript.

Funding

This study was funded by the University of Southern Denmark. The funder played no role in the design, conduct, or reporting.

Compliance with Ethical Standards

Conflict of Interest

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf: The authors declare that they do not have a conflict of interest.

Supplementary material

11606_2019_5024_Fig4_ESM.png (213 kb)
Supplementary Figure 4

Funnel Plots of hazard ratios for Investigation of Publication Bias (PNG 212 kb)

11606_2019_5024_MOESM1_ESM.tif (160 kb)
High resolution image (TIF 160 kb)
11606_2019_5024_MOESM2_ESM.docx (325 kb)
ESM 1 (DOCX 325 kb)

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Copyright information

© Society of General Internal Medicine 2019

Authors and Affiliations

  • Morten Rix Hansen
    • 1
    • 2
    • 3
    Email author
  • Asbjørn Hróbjartsson
    • 4
    • 5
    • 6
  • Anton Pottegård
    • 1
  • Per Damkier
    • 2
    • 7
  • Kasper Søltoft Larsen
    • 1
  • Kenneth Grønkjær Madsen
    • 1
  • René dePont Christensen
    • 8
  • Malene Elisa Lopez Kristensen
    • 1
  • Palle Mark Christensen
    • 1
  • Jesper Hallas
    • 1
    • 2
  1. 1.Clinical Pharmacology and PharmacyUniversity of Southern DenmarkOdenseDenmark
  2. 2.Department of Clinical Biochemistry and PharmacologyOdense University HospitalOdenseDenmark
  3. 3.Department of Clinical PharmacologyAarhus University HospitalAarhusDenmark
  4. 4.Center for Evidence-Based Medicine OdenseUniversity of Southern DenmarkSønderborgDenmark
  5. 5.Department of Clinical ResearchUniversity of Southern DenmarkSønderborgDenmark
  6. 6.Odense Explorative Patient data Network (OPEN)Odense University HospitalOdenseDenmark
  7. 7.Department of Clinical ResearchUniversity of Southern DenmarkSønderborgDenmark
  8. 8.Research Unit for General PracticeOdenseDenmark

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