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
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
I am struck by the quality of this study with respect to methodological details and statement of limitations. Nonetheless, missing, as far as I could tell, is mention of the possible effectiveness of the combination of exercise and drug interventions. Why does it have to be a treatment choice between exercise and drug interventions? I wonder if the individual studies underlying the meta-analyses that were the basis for the current metaepidemiological study contain the necessary data to tease out the combined effect of exercise and drug interventions. I would have thought the authors would have at least considered it as a candidate for future research.
Competing interests: No competing interests
Naci H, et al investigated to determine the comparative effectiveness of exercise versus
drug interventions on mortality outcomes. They included 16 (four exercise and 12 drug) meta-analyses and included 305 randomised controlled trials with 339 274 participants. They observed that 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 and exercise v antiplatelets 0.10). Diuretics were more effective than exercise in heart failure (exercise vs diuretics 4.11). They concluded that 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.1
This study points the importance of therapeutic life style changes compared with drugs intervention. All physicians should think about this message in time of many drugs being prescribed while elderly population is increasing fast and life expectancy is longer. In this regard, statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are very important and so, most frequently prescibed to prevent cardiovascular events in patients with high risk or even low risk of vascular disease by reducing low density lipoprotein cholesterol.2,3 Therefore, The 2013 American guidelines recommend to use high-intensity statin therapy and extend to use in more people.4 However, European worried about the potential side effects of statins in a large fraction of population for a life-long period.5 This is true to Asian people including Korean and Japanese in whom cholesterol levels and the prevalence of cardiovascular disease are still lower albeit both are increasing now.
Unwanted effects of statins have been neglected over the decade and nowadays, these off-target effects are being focused. Statin treatment are associated with deterioration of glucose homeostasis and increased risk of diabetes mellitus.6-8 Experimental and clinical studies have suggested these off-target effects are dose-dependent.9-13 A very recent study reported that after adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new-onset diabetes (hazard ratio 1.23 and 1.32, respectively).14 Most recently, renal insult by statin treatment has been suggested in contrast to the previous studies showing the renoprotective effect.15 These off-target effects are also dose-dependent. The use of high potency statins was associated with an increased rate of diagnosis for acute kidney injury in hospital admissions compared with low potency statins.
With current evidence, it is difficult to weigh the possible adverse renometabolic effects of statin on overall mortality in a quantitative manner. In the primary prevention studies, the use of statins is controversial: favoring3 or not favoring16,17 statins. According to a current meta-analysis on this issue, as compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number needed to treat per year for intensive-dose statin therapy was 155 for cardiovascular events.12 This data support that lipid lowering effect of statins outweighs adverse renometabolic effect of statins. Of note, it would be prudent to consider current cardiorenometabolic status and natural histroy of diseases in each individual when choosing statin therapy for optimal individual patient health over the long-term. Indeed, therapeutic life style changes may be potentially as effective as many drug interventions on the secondary prevention of coronary heart disease, stroke, heart failure, and prediabetes.1
Funding: None, Disclosures: None
REFERENCES
1. Naci H, Ioannidis JPA. Comparative effectiveness of exercise and drug
interventions on mortality outcomes: metaepidemiological study. BMJ 2013;347:f5577
2. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670-81.
3. Cholesterol Treatment Trialists' (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012;380:581-90.
4. Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013, doi: 10.1161/01.cir.0000437738.63853.7a.
5. http://us5.campaign-archive2.com/?u=5722525cab46445583feb00fd&id=4c6ab38...
6. Koh KK, Sakuma I, Quon MJ. Differential metabolic effects of distinct statins. Atherosclerosis 2011;215:1-8.
7. Lim S, Sakuma I, Quon MJ, Koh KK. Potentially important considerations in choosing specific statin treatments to reduce overall morbidity and mortality. Int J Cardiol 2013;167: 1696-1702.
8. Lim S, Sakuma I, Quon M, Koh KK. Differential metabolic actions of specific statins: clinical and therapeutic considerations. Antioxid Redox Signal 2013 Aug 7. [Epub ahead of print]
9. Yada T, Nakata M, Shiraishi T, Kakei M. Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2+ signalling and insulin secretion due to blockade of L-type Ca2+ channels in rat islet beta-cells. Br J Pharmacol 1999;126:1205-13.
10. Koh KK, Quon MJ, Han SH, et al. Simvastatin improves flow-mediated dilation but
reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients. Diabetes
Care 2008;31:776-82.
11. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol 2010;55:1209-16.
12. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011;305:2556-64.
13. Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ 2013;346:f2610.
14. Shen L, Shah BR, Reyes EM, Thomas L, Wojdyla D, Diem P, et al. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ 2013;347:f6745.
15. Dormuth CR, Hemmelgarn BR, Paterson JM, James MT, Teare GF, Raymond CB, et al; Canadian Network for Observational Drug Effect Studies. Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ 2013;346:f880.
16. Culver AL, Ockene IS, Balasubramanian R, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med 2012;172:144-52.
17. Goldstein MR, Mascitelli L. Do statins cause diabetes? Curr Diab Rep 2013;13:381-90.
Competing interests: No competing interests
I would like to add something about the barriers erected to patient's taking up exercise, from the point of view of a patient's relative.
A patient who may be anxious about being able to control their exercise - about not being in control, and putting excessive stress on their body at a time when they feel vulnerable - may prefer to join a gym or organised exercise activities.
Unfortunately, many gyms now require members or prospective members who admit to health problems such as hypertension or cancer to provide a doctor's note, effectively assuring the gym that the patient will not die or suffer a stroke or myocardial infarction while at the gym, and indemnifying them should this occur.
There is a paucity of information about how much or how intense exercise patients with many conditions should undertake, leaving their doctors uncertain what they can safely say.
Not only do doctors have no crystal ball, and cannot provide assurances that the patient will definitely not get ill or die in the gym; but providing a letter to indemnify the gym is not NHS work, so they are free to decline to do so, or to charge the patient.
Competing interests: No competing interests
We agree with Nunan and colleagues that causal inferences from randomized trials can be jeopardized by limitations in methodological quality in their design, conduct, analysis, and reporting, leading to underestimation or overestimation of the true intervention effect, i.e., bias. Unsurprisingly, none of the exercise trials identified in our review had double blinding (it would be impossible to mask patients to exercise interventions), and only a small number of trials blinded the assessors. However, meta-epidemiological reviews have demonstrated that methodological quality attributes (including blinding) do not seem to influence much the magnitude of objective outcomes such as mortality (this is in contrast to subjective outcomes where limitations in blinding and allocation concealment result in exaggerated treatment effects) [1, 2].
The important consideration in our network meta-analysis is whether the randomized trials of drug and exercise interventions have a balanced distribution of relative treatment effect modifiers [3]. We considered conceptual heterogeneity in terms of trial eligibility criteria, follow-up duration, blinding practices, and patient characteristics reflecting baseline disease severity. Patient population characteristics were broadly similar in all conditions except for stroke where patients participating in exercise trials had less severe disability compared to those included in drug trials [4]. All drug trials included in our review had participants with ischemic strokes.
There was generally more variability within individual meta-analyses than there was between meta-analyses of drug and exercise interventions in terms of patient population and trial characteristics. In cases where differences were observed between the trials of drug and exercise interventions (differences in terms of trial follow-up duration and blinding practices), these differences did not translate to statistical heterogeneity in effect size estimates. We have also statistically evaluated the consistency of direct and indirect evidence included in every closed loop in our network meta-analyses, and confirmed the lack of evidence of inconsistency.
Byatt and colleagues questioned why ACE inhibitors showed no mortality benefit in our analysis. Our objective was not to test the mortality benefits of exercise and drug interventions alone – this was done in the primary meta-analyses included in our review. Our analysis on ACE inhibitors was based on the 1-year survival benefits of ACE inhibitors reported by Flather and colleagues [5]. The magnitude of mortality benefits in our analysis closely parallel those in this earlier meta-analysis. The wider credible interval reflects our conservative approach in adopting random-effects Bayesian network meta-analyses, which often results in wider 95% uncertainty estimates. This also explains why the 95% CrI around the mortality benefit of exercise interventions in coronary heart disease crosses 1.00 unlike the original meta-analysis on which it is based.
Although Byatt and colleagues also state that no time scale was given for the mortality benefits reported in our study, these are provided in our online appendices. Average trial follow-up duration was generally similar across drug and exercise meta-analyses. For each condition, average trial follow-up duration was never the shortest for exercise trials (24 months in trials of coronary heart disease; ~6 months in trials of stroke; ~12 months in trials of heart failure; and > 2 years in trials of pre-diabetes).
Muhlhauser and Meyer suggest that meta-analyses of complex interventions may be obsolete due to heterogeneity. We do not share this view. Heterogeneity can be helpful in identifying important relative treatment effect modifiers. Regardless, in our review, there was little statistically detectable between-study heterogeneity among the trials of exercise-based interventions. We acknowledge that modest heterogeneity is almost always difficult to exclude. However, the observed consistency of the results may suggest that factors that are typically considered relative treatment effect modifiers do not in fact influence much the treatment effects. Moreover, there is no evidence to suggest that exercise interventions are confounded by intensification of care, which is likely due to successful trial practices ensuring that the type, intensity, and frequency of drug interventions were similar in exercise and control arms of randomized trials. Finally, objective outcomes such as mortality are largely immune to many potential biases in methodological quality attributes of trials [1, 2].
Muhlhauser and Meyer also suggest that the randomized trials of exercise interventions “are likely to be performed by people who want to proof of benefit of exercise.” To the extent that this is a problem, it would be important to point out that the randomized trials of drugs are almost exclusively performed by pharmaceutical companies that have clear financial conflicts of interests in the findings of their randomized controlled trials. It has been shown time and again that pharmaceutical companies exclusively sponsor trials that have favorable conclusions for their products [6, 7]. Industry sponsorship creates asymmetries in the evidence base, with some companies selectively comparing their products against others that they deem straw man competitors – in a consistent manner with the recent concern voiced by Light and Lexchin, postulating that much of the research and development activities of pharmaceutical companies are driven by marketing and sales motives [8].
As Hopayian suggests, more research is needed – particularly to investigate the “formulation” and “dose” of different types exercise interventions that may work as well or better than commonly prescribed drugs. We hope that our paper prompts increased discussion and data collection to eventually foster improved comparisons between drug and exercise interventions. In addition to the need to invest in large randomized controlled trials directly comparing drug and exercise interventions in a wide range of illnesses, we hope that researchers undertake similar reviews; expand the breadth and depth of our analysis; and embark upon a research agenda that compares the benefits and harms of pharmacological and non-pharmacological interventions. We agree with the importance of systematically exploring the impact of exercise interventions on additional outcomes beyond mortality. To this end, we look forward to the findings of the systematic review that Nunan and colleagues are undertaking [9].
Huseyin Naci and John PA Ioannidis
References:
[1] Savović J, Jones HE, Altman DG, Harris RJ, Jüni P, Pildal J, Als-Nielsen B, Balk EM, Gluud C, Gluud LL, Ioannidis JP, Schulz KF, Beynon R, Welton NJ, Wood L, Moher D, Deeks JJ, Sterne JA. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Ann Intern Med. 2012 Sep 18;157(6):429-38.
[2] Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, Gluud C, Martin RM, Wood AJ, Sterne JA. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ. 2008 Mar 15;336(7644):601-5.
[3] Jansen JP, Naci H. Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers. BMC Med. 2013 Jul 4;11:159.
[4] Naci H, Ioannidis JPA. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ 2013,347:15577.
[5] Flather MD, Yusuf S, Køber L, Pfeffer M, Hall A, Murray G, Torp-Pedersen C, Ball S, Pogue J, Moyé L, Braunwald E. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet. 2000 May 6;355(9215):1575-81.
[6] Lathyris DN, Patsopoulos NA, Salanti G, Ioannidis JP. Industry sponsorship and selection of comparators in randomized clinical trials. Eur J Clin Invest. 2010 Feb;40(2):172-82.
[7] Stamatakis E, Weiler R, Ioannidis JP. Undue industry influences that distort healthcare research, strategy, expenditure and practice: a review. Eur J Clin Invest. 2013 May;43(5):469-75.
[8] Light DW, Lexchin JR. Pharmaceutical research and development: what do we get for all that money? BMJ. 2012 Aug 7;345:e4348.
[9] 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
We read this paper with interest and initially found the results fascinating - especially the implication that exercise might be almost an order of magnitude more effective than drug treatment in reducing subsequent mortality.
However, after discussing the paper we were left with some further concerns about its rigour, in addition to those already mentioned in the earlier responses by Mühlhauser, Nunan and Hopayian:
Firstly, no time scale was given for any of the mortality effects described. Unless mortality rates are linear over time with any of the conditions studied, not defining the time frame means that the magnitude of the effect cannot usefully be extrapolated to clinical practice.
Secondly, to conflate 'placebo' and 'usual care' as the control comparator group is surely illogical? We wonder whether this is the reason that ACE inhibitor treatment showed no mortality benefit in this network meta-analysis, despite an earlier systematic review showing some 25% reduction in odds ratios for mortality in patients with heart failure or systolic dysfunction treated with ACE inhibitors compared to placebo[1], and the specific mention that they 'improve survival rate' in the current NICE chronic heart failure guideline[2]. Why not try to show if there's a difference between placebo and usual treatment in the network meta-analysis in order to clarify this distinction?
Finally, and as a variation on the preceding point, this analysis apparently treats all strokes as being equal with respect to mortality. This is potentially inappropriate, for several reasons (not least that the baseline disease severity of patient populations was "considerably different in stroke trials"), and there might also be reason to expect exercise to affect both the cellular response of different subtypes of stroke, the degree of spontaneous recovery, and the potential for uptake of exercise.
Until these systematic potential sources of variance are discussed and accounted for (perhaps testing the potential magnitude of any of these effects with sensitivity analyses), it is impossible to know how much credence to give to these apparently intriguing results.
Branavan Anandasundaram, Mehreen Hayat, and Kit Byatt, on behalf of the Hereford County Hospital Journal Club
1. Flather MD, Yusuf S, Køber L, Pfeffer M, Hall A, Murray G, Torp-Pedersen C, Ball S, Pogue J, Moyé L, Braunwald E. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet. 2000 May 6;355(9215):1575-81.
2. NICE Clinical Guideline No 108. CHRONIC HEART FAILURE. August 2010. http://guidance.nice.org.uk/CG108 (accessed 28 Oct 13)
Competing interests: No competing interests
The obvious intention of the authors of this meta-analysis to stress the need for more and better effectiveness and comparative studies on exercise is well appreciated. However, the methodological approach used in this metaepidemiological study does not generate valid information. The results are biased and misleading.
The authors compare complex interventions with single component drug interventions. Evaluation of complex interventions requires specific considerations [1]. Meta-analysis of complex interventions may be obsolete due to clinical heterogeneity and incomplete information [2]. The exercise studies included in this meta-analysis suffer from all problems inherent to complex behavioural interventions. Exercise is by itself a complex intervention and often part of multicomponent treatment regimens. The intervention is not blinded, most studies lack an appropriate sham intervention, and studies are likely to be performed by people who want to proof benefit of exercise. Without appropriate control interventions exercise treatment is inevitably confounded by intensification of care which usually improves adherence to drugs and other therapies. Exercise studies may include healthier patients than drug trials. Additional to these shortcomings the studies included in the present meta-analysis demonstrate a substantial risk of bias. The related systematic reviews report that most exercise studies are characterized by unclear randomisation procedure, lack of blinding, high drop-out rates and no intention-to-treat analysis. Publication bias is likely. Accompanying treatments including dosing and adherence to prescribed therapies are rarely reported. In contrast, most drug trials had a low risk of bias and as single component interventions were less likely to be prone to confounding.
Due to the substantial limitations of the quality of exercise intervention trials the conclusions of the present meta-analysis are not justified. Systematic reviews have to acknowledge the quality of the included studies and with regard to exercise the specific methodological challenges related to complex interventions.
1)Craig P, Dieppe P, Macintyre S, Michie S, Nazareth I, Petticrew M: Developing and evaluating complex interventions: the new Medical Research Council guidance. BMJ 2008; 337:a1655.
2)Lenz M, Steckelberg A, Richter B, Mühlhauser I. Meta-analysis does not allow appraisal of complex interventions in diabetes and hypertension self-management: a methodological review. Diabetologia 2007; 50: 1375-1383
Ingrid Mühlhauser, MD, PhD, professor
Unit of Health Sciences and Education
University of Hamburg
Martin-Luther-King Platz 6
D-20146 Hamburg
Germany
Email: Ingrid_Muehlhauser@uni-hamburg.de
Gabriele Meyer, PhD, professor
Faculty of Medicine
Institute for Health and Nursing Science
Martin-Luther-University Halle-Wittenberg
Magdeburger Straße 8
D-06110 Halle (Saale)
Germany
Email: Gabriele.Meyer@medizin.uni-halle.de
Competing interests: No competing interests
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
While Naci and Ioannides’ network analysis of meta-analyses comparing the effects of exercise against medication on mortality is an important landmark, there are a few problems that should be considered.
First, one inclusion criterion is debatable. When more than one meta-analysis was available, they chose the most recent. An alternative would have been to choose on the basis of quality. At the very least, it is desirable to see a quality assessment of the meta-analyses and a consideration of how that might have affected the results.
Second, lumping all forms of exercise without consideration of the “formulation” and “dose”, to borrow terms from drug prescribing, left the study open to misclassification bias, with a tendency to underestimate the effects of the efficacious forms of exercise. The authors allude to this themselves.
Third, I wonder if they have over-extended their conclusion with “our analysis suggests that exercise potentially had similar effectiveness to drug interventions”. What it demonstrated was that, barring two exceptions, there was no difference between the two options. To demonstrate similarity, a non-inferiority study would be needed.
Competing interests: No competing interests
The final declaration of Naci and Ioannidis that, "based on available data (339,274 participants) on the secondary prevention of coronary heart disease, stroke, heart failure and prediabetes, physical activity is potentially as effective as many drug interventions" conveys a clear and significant message not only to the clinicians but also to the stake holders of medical education.
We are all well aware of the minuscule attention reluctantly provided to the subject "physical activity" in the medical school curriculum.
There is ample evidence indicating the pre-eminence of physical activity in the therapeutic armamentarium of our great Greek teachers of medicine.
It is up to contemporary medical mentors to lead followers to the "physical activity arena."
Competing interests: No competing interests
Re: Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study
The denominator for those testing for exercise is much smaller than those testing for drug intervention. This probably could have been because of difficulty of sustaining the consistency of exercising, as this depends with individuals, as some individuals tend to go back to their initial culture of laziness and fatigue at the process of exercising. The author needs to demonstrate how we need to take exercise seriously because the paradigm in medical research is focused on drug trials. That's where the funding is, and that's what influences clinician behavior.
The environment in which the research took place could have been unfavorable for exercise intervention thus influencing the denominator and the results. Luck of supervisor and too much of luxuriance life could be non conducive and therefore influencing the results. There is need to put some control measures such as supervision to take care of this.
Between exercise and drug, I believe that each intervention is more effective for a certain disease more than the other. According to a study Huseyin Naci 2013, exercise was as effective as any of the key drugs used to treat coronary heart disease in reducing the risk of death among those patients. Among stroke patients, exercise programs seem to be more effective than the two usual groups of pharmacological therapy. For patients with heart failure, the group of diuretic drugs needs to be more effective than exercise, but exercise is as effective as other usual drug treatments.
Finally exercise was no different to other treatments for mortality outcomes in people with prediabetes. I would recommend this study in Kenya, expecially in areas where their is high rate of mortlaity from diseases such as coronary heart disease, stroke and heart failure.
Competing interests: No competing interests