Dataset Information

Comparative Effectiveness of Medical Therapy, Supervised Exercise, and Revascularization for Patients With Intermittent Claudication: A Network Meta-analysis.

ABSTRACT:

Background

There are limited data on the comparative effectiveness of medical therapy, supervised exercise, and revascularization to improve walking and quality of life in patients with intermittent claudication (IC).

Hypothesis

Supervised exercise and revascularization was superior to medical therapy in IC.

Methods

We studied the comparative effectiveness of exercise training, medications, endovascular intervention, and surgical revascularization on outcomes including functional capacity (walking distance and timing), quality of life, and mortality. We searched PubMed, EMBASE, and the Cochrane Database of Systematic Reviews from January 1995 to August 2012 for relevant English-language studies. Two investigators independently collected data. Meta-analyses with random-effects models of direct comparisons were supplemented by mixed-treatment analyses to incorporate data from placebo comparisons, head-to-head comparisons, and multiple treatment arms.

Results

Thirty-five unique studies evaluated treatment modalities in 7475 patients with IC. Compared with usual care, only exercise training improved both maximal walking distance (150 meters; 95% confidence interval: 35-266 meters, P = 0.01) and initial claudication distance (39 meters; 95% confidence interval: 9-65 meters, P = 0.003). All modalities were associated with improved quality of life (Short Form-36 physical functioning score) compared with usual care, but there were no differences between treatments. There were insufficient safety data to assess treatment-related complications. All-cause mortality was not significantly different between modalities.

Conclusions

Evidence is insufficient to determine treatment superiority for improving quality of life and walking parameters in IC patients. Further studies with attention to study design, standardized efficacy and safety endpoints, and appropriate subgroup reporting are necessary to determine comparative effectiveness.

SUBMITTER: Vemulapalli S

PROVIDER: S-EPMC6711096 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveSupervised exercise therapy (SET) is the first line treatment for intermittent claudication owing to peripheral arterial disease. Despite multiple randomized controlled trials proving the efficacy of SET, there are large differences in individual patient's responses. We used plasma metabolomics to identify potential metabolic influences on the individual response to SET.MethodsPrimary metabolites, complex lipids, and lipid mediators were measured on plasma samples taken at before and after Gardner graded treadmill walking tests that were administered before and after 12 weeks of SET. We used an ensemble modeling approach to identify metabolites or changes in metabolites at specific time points that associated with interindividual variability in the functional response to SET. Specific time points analyzed included baseline metabolite levels before SET, dynamic metabolomics changes before SET, the difference in pre- and post-SET baseline metabolomics, and the difference (pre- and post-SET) of the dynamic (pre- and post-treadmill).ResultsHigh levels of baseline anandamide levels pre- and post-SET were associated with a worse response to SET. Increased arachidonic acid (AA) and decreased levels of the AA precursor dihomo-γ-linolenic acid across SET were associated with a worse response to SET. Participants who were able to tolerate large increases in AA during acute exercise had longer, or better, walking times both before and after SET.ConclusionsWe identified two pathways of relevance to individual response to SET that warrant further study: anandamide synthesis may activate endocannabinoid receptors, resulting in worse treadmill test performance. SET may train patients to withstand higher levels of AA, and inflammatory signaling, resulting in longer walking times.Clinical relevanceThis manuscript describes the use of metabolomic techniques to measure the interindividual effects of SET in patients with peripheral artery disease (PAD). We identified high levels of AEA are linked to CB1 signaling and activation of inflammatory pathways. This alters energy expenditure in myoblasts by decreasing glucose uptake and may induce an acquired skeletal muscle myopathy. SET may also help participants tolerate increased levels of AA and inflammation produced during exercise, resulting in longer walking times. This data will enhance understanding of the pathophysiology of PAD and the mechanism by which SET improves walking intolerance.