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

BMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f5577 (Published 01 October 2013) Cite this as: BMJ 2013;347:f5577

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

Epidemiological studies inform us that being physical active improves longevity[1] and underpin international recommendations to tackle the growing epidemic of inactivity.[2]

It was therefore promising that the Naci metaepedimioligical study in the BMJ indicated exercise is as effective as drug therapy for mortality outcomes.[3]

The study has gone to great effort to address the comparative effectiveness of exercise and drug therapies; but the reported effects are limited by the lack of appropriate and available data. For example, out of 305 trials, only two directly compared an exercise intervention with a drug therapy.

As a further example the authors highlight that following a stroke, exercise was more effective than drug interventions. A closer look shows that one review identified just two trials for exercise versus a control on mortality outcome with a mean follow up of 9 months, less than 50 patients per arm and a total of 8 deaths (2 in the exercise arm, 6 in the control).[4] This equates to a control group risk of 8% and a relative risk reduction of 0.7. A sufficiently powered study would need at least 200 patients per arm, follow up for at least 4 years or a group of higher risk patients.[5] This compares with a review of nine trials for antiplatelet drug therapy with a total of 41,399 patients and 5,159 deaths (2,497 in drug arm, 2,662 in control arm).[6]

The methodological issues (e.g. insufficient allocation concealment, weak randomisation procedures) indicate a high risk of bias in the exercise studies and patients often differed in severity of disease compared with those in drug trials.

For a number of chronic conditions, mortality is not the only endpoint of clinical concern, and this paper is limited by having it as their sole outcome measure. For example, a patient with debilitating osteoarthritis is more likely to be concerned with functional capacity, pain and quality of life outcomes.

In their favour the authors highlight some of these limitations. One of the key limitations is the lack of information on the nature of effective interventions in terms of type, intensity and duration of activity and the conditions/settings for which exercise had a positive or negative effect. We believe such data might be available by expanding outcomes to include other important factors across a broader range of conditions that could benefit from a physical activity intervention and are working towards this.[7]

Finally, and as touched upon by the authors, the findings of this paper do not provide evidence that patients currently on medication should stop them in favour of exercise.

1. Lee I-M, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 2012;380:219-229.
2. Global Recommendations on Physical Activity for Health. In. Geneva: World Health Organisation;2010:60.
3. Naci H, Ioannidis JPA. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ 2013,347:15577.
4. Brazzelli M, Saunders DH, Greig CA, Mead GE. Physical fitness training for stroke patients. Cochrane Database Syst Rev 2011(11):CD003316.
5. Glasziou P, Doll H. Was the study big enough? Two café rules. Evid Based Med 2006,11:69-70.
6. Sandercock P, Gubitz G, Foley P, Counsell C. Antiplatelet therapy for acute ischaemic stroke. Cochrane Database Syst Rev 2008(4):CD000213.
7. Nunan D, Mahtani KR, Roberts N, Heneghan C. Physical activity for the prevention and treatment of major chronic disease: an overview of systematic reviews study protocol. Systematic Reviews 2013,2:56.

Competing interests: No competing interests

11 October 2013
David Nunan
Research fellow
Kamal R Mahtani, Carl Heneghan
University of Oxford
Radlcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG