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Exercise, drug interventions may produce similar outcomes on mortality
A new review of existing trial evidence found that in many cases exercise and drug interventions appear to have similar mortality benefits in the prevention of CHD and diabetes, rehabilitation after stroke and treatment of HF.
Researchers reviewed 16 meta-analyses (four related to exercise interventions, 12 related to drug interventions) covering 305 randomized controlled trials with 339,274 participants.
According to the data, there was no difference between exercise and drug interventions in the prevention of diabetes or the secondary prevention of CHD.
Among patients with stroke, the researchers found physical activity interventions were more effective at preventing mortality than drug interventions (OR for exercise vs. anticoagulants=0.09; 95% credible interval, 0.01-0.7; OR for exercise vs. antiplatelets=0.1; 95% credible interval, 0.01-0.62).
Among patients with HF, the researchers found diuretics were more effective at preventing mortality than exercise (OR=4.11; 95% credible interval, 1.17-24.76). However, there were no differences in effectiveness between exercise and ACE inhibitors, beta-blockers or angiotensin receptor blockers.
This study “highlights the near absence of evidence on the comparative effectiveness of exercise and drug interventions on mortality outcomes,” the researchers wrote in the study.
A limitation of the study is that most trials have not directly compared outcomes for exercise interventions against outcomes for drug interventions. Therefore, “it remains a possibility that potential imbalances in the distribution of unobserved or unmeasured effect modifiers across the contrasts affected the findings, potentially confounding the comparative estimates between drugs and exercise,” they wrote. “Accordingly, we caution that the comparison of exercise and drug interventions should be tempered by the additional differences in patient populations across different trials.”
Disclosure: The researchers report no relevant financial disclosures.
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The conclusion that there was no difference in outcome between exercise interventions and drug interventions is overstated and not supported by their own meta-analysis. Clearly, the data are far superior for the No. 1 cause of death (CVD), with an estimate of 19% improvement in outcomes with drug interventions and a nonsignificant improvement of 11% with exercise. Furthermore, there are no head-to-head data of physical activity vs. exercise. So, the conclusions should be restated to say that there are some data to suggest that physical activity interventions may be comparable to drug interventions, but these will depend on results of large-scale clinical trials. Their statement that “Exercise interventions should therefore be considered as a viable alternative to, or alongside, drug therapy,” is a dangerous overstatement of the available evidence. You cannot use a meta-analysis to recommend a change in guidelines or therapy, and without head-to-head data, the best one can say is that a prospective trial is warranted.
Having said all that, I think the authors did a nice job of showing the potential benefit of physical activity. I agree with the authors’ assertion that exercise interventions deserve more focus and clearly demonstrate a cogent benefit and should be used much more frequently as an adjunctive therapy. I just think trying to say that exercise can replace drug therapy is taking their own personal biases too far in the opposite direction.
This paper points out the largest problem and limitation with meta-analyses — that combining unlike groups sometimes results in erroneous conclusions. For example, there are no current data that diuretics improve HF significantly, and the Blood Pressure Lowering Treatment Trialists' Collaboration (Lancet. 2003;362:1527-1535) concluded that ACE inhibitors and beta-blockers were far superior for outcomes related to congestive HF than diuretics. However the authors find, in three small trials encompassing only 202 patients, that diuretics lead to an 81% improvement in outcomes with congestive HF. This is erroneous, and yet the authors base a large number of their conclusions on this incorrect finding. It is well known in cardiology that ACE inhibitors and beta-blockers produce far better results than diuretics. Making any recommendations regarding stopping or replacing current proven medications with physical activity is very inappropriate. Their data that anticoagulants don’t improve stroke are also probably erroneous and based on only including certain studies. It is well established that oral anticoagulants reduce stroke by 62% to 68% in atrial fibrillation, far exceeding any possible physical activity benefit.