Review: Exercise reduces mortality compared with drugs in stroke but not in CHD, HF, or prediabetes

Naci H, Ioannidis JP. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ. 2013;347:f5577.

Clinical impact ratings: F ★★★★★★✩ e ★★★★★★✩ Question

Main results

How do exercise and drugs compare for reducing mortality?

Results of network meta-analyses are shown in the Table.

Review scope


Included studies compared exercise or drugs with control (placebo or usual care) or each other and reported mortality as an outcome.

Exercise reduces mortality compared with drugs in stroke. Diuretics reduce mortality compared with exercise in heart failure. Exercise and drugs do not differ for mortality in coronary heart disease secondary prevention or prediabetes.

Review methods MEDLINE was searched to Dec 2012 for meta-analyses of randomized controlled trials (RCTs) of exercise. The following searches were limited to conditions in which exercise was evaluated for reducing mortality (stroke, heart failure, prediabetes, and secondary prevention of coronary heart disease [CHD]). Cochrane Database of Systematic Reviews and MEDLINE were searched for meta-analyses of RCTs of drugs. RCTs from the most recent meta-analyses for each condition and intervention were considered for inclusion. MEDLINE was then searched to May 2013 for recent RCTs. 305 RCTs (n = 339 274) met the selection criteria: 57 (n = 14 716) evaluated exercise, 3 (n = 5393) compared exercise with drugs, and the remainder evaluated drugs. Exercise interventions varied in content, frequency, and duration. 199 RCTs (n = 172 771, follow-up duration 7 d to 72 mo in 122 RCTs) were done in CHD secondary prevention, 30 (n = 77 621, followup duration 10 d to 12 mo) in stroke, 66 (n = 56 752, followup duration < 12 mo to 4 y in 21 RCTs) in heart failure, and 10 (n = 32 130, follow-up duration 2.8 y to 6 y) in prediabetes. Data from direct and indirect treatment comparisons were combined using Bayesian network meta-analysis. Network meta-analyses of exercise vs comparators for mortality* Conditions Coronary heart disease


Heart failure


OR (95% CrI)

Placebo/usual care

0.89 (0.76 to 1.04)


1.08 (0.90 to 1.30)


1.05 (0.87 to 1.25)


1.08 (0.87 to 1.33)


1.07 (0.88 to 1.30)

Placebo/usual care

0.09 (0.01 to 0.72)


0.09 (0.01 to 0.70)


0.10 (0.01 to 0.62)

Placebo/usual care

0.79 (0.59 to 1.00)


1.11 (0.82 to 1.46)


0.89 (0.59 to 1.23)


0.86 (0.62 to 1.16)

Diuretics Prediabetes

4.11 (1.17 to 25)

Placebo/usual care

0.67 (0.22 to 1.27)


0.73 (0.14 to 1.96)

α-glucosidase inhibitors

0.22 (0.02 to 1.18)

Biguanides Glinides

2.67 (0.41 to 36) 0.69 (0.10 to 2.52)

Source of funding: No external funding. For correspondence: Dr. H. Naci, London School of Economics Health, London, England, UK. E-mail [email protected]

Commentary Naci and Ioannidis used network meta-analysis to synthesize the limited evidence on the effects of exercise on mortality outcomes, particularly compared with drugs. They searched MEDLINE and Cochrane databases comprehensively; there is no mention of searching reference lists of relevant studies, contacting experts, or searching for unpublished studies or studies in languages other than English, so important studies could have been missed. Randomized design was an inclusion criterion, but the authors did not report on completeness of follow-up in included studies. The exercise interventions varied widely in setting, mode, frequency, intensity, and duration of activity. This calls into question the appropriateness of combining the studies and makes it harder to translate the data into a clinical bottom line. Studies that met inclusion criteria covered only 4 conditions. Only 227 patients with stroke were included in exercise trials, so these results should be interpreted with caution. Results are more robust for heart failure, CHD, and prediabetes as larger numbers of patients with these conditions were included in exercise trials. The take-home message of this review is that exercise seems to be more important than drugs for patients with stroke, as important as drugs for secondary prevention of CHD and prevention of diabetes, and less effective than diuretics for patients with heart failure. Despite the limitations of the network meta-analysis, it provides potentially useful knowledge for counselling patients with these conditions. However, what does “exercise” mean? The specific form of exercise is undefined: Using what is detailed in current guidelines seems reasonable. We can only hope for more specific trials, such as that by Lian and colleagues (1). For conditions other than the 4 evaluated, uncertainty about the effect of exercise on mortality remains. John F. Cox III, MD University of Rochester School of Medicine Rochester, New York, USA Reference 1. Lian XQ, Zhao D, Zhu M, et al. The influence of regular walking at different times of day on blood lipids and inflammatory markers in sedentary patients with coronary artery disease. Prev Med. 2014;58:64-9.

*ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin-receptor blocker; CrI = credible interval; OR = odds ratio; other abbreviations defined in Glossary. Data were pooled using random-effects models and Bayesian methods with direct and indirect treatment comparisons. OR < 1 indicates benefit with exercise.

15 April 2014 | ACP Journal Club | Volume 160 • Number 8

© 2014 American College of Physicians

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