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Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study

BMJ 2013; 347 doi: (Published 01 October 2013) Cite this as: BMJ 2013;347:f5577
  1. Huseyin Naci, researcher1, fellow2,
  2. John P A Ioannidis, director3
  1. 1LSE Health, London School of Economics and Political Science, London, UK
  2. 2Drug Policy Research Group, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
  3. 3Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA
  1. Correspondence to: H Naci h.naci{at}
  • Accepted 22 August 2013


Objective To determine the comparative effectiveness of exercise versus drug interventions on mortality outcomes.

Design Metaepidemiological study.

Eligibility criteria Meta-analyses of randomised controlled trials with mortality outcomes comparing the effectiveness of exercise and drug interventions with each other or with control (placebo or usual care).

Data sources Medline and Cochrane Database of Systematic Reviews, May 2013.

Main outcome measure Mortality.

Data synthesis We combined study level death outcomes from exercise and drug trials using random effects network meta-analysis.

Results We included 16 (four exercise and 12 drug) meta-analyses. Incorporating an additional three recent exercise trials, our review collectively included 305 randomised controlled trials with 339 274 participants. Across all four conditions with evidence on the effectiveness of exercise on mortality outcomes (secondary prevention of coronary heart disease, rehabilitation of stroke, treatment of heart failure, prevention of diabetes), 14 716 participants were randomised to physical activity interventions in 57 trials. No statistically detectable differences were evident between exercise and drug interventions in the secondary prevention of coronary heart disease and prediabetes. Physical activity interventions were more effective than drug treatment among patients with stroke (odds ratios, exercise v anticoagulants 0.09, 95% credible intervals 0.01 to 0.70 and exercise v antiplatelets 0.10, 0.01 to 0.62). Diuretics were more effective than exercise in heart failure (exercise v diuretics 4.11, 1.17 to 24.76). Inconsistency between direct and indirect comparisons was not significant.

Conclusions Although limited in quantity, existing randomised trial evidence on exercise interventions suggests that exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.


  • We thank Anthony J Damico (Kaiser Family Foundation, Washington DC, USA) for his contribution to the systematic review, evaluation of the geometry of the existing evidence, and his comments on an earlier version of this paper; and Ingrid Hopper and colleagues for sharing data from their published meta-analysis.

  • Contributors: HN conceived the study. JPAI provided guidance during study design, protocol development, analysis, interpretation, and manuscript preparation. HN and Anthony J Damico identified and selected studies for inclusion in the review. HN extracted data from included meta-analyses, and Anthony J Damico checked for accuracy. HN did all of the statistical analyses. HN and JPAI interpreted the findings. HN drafted the paper and JPAI made revisions on subsequent drafts. Both authors read and approved the final version of the paper. HN is the guarantor.

  • Funding: This study received no funding.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: Raw data used in the analysis is available on request from the corresponding author at h.naci{at}

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