Benefits and harms of exercise therapy in people with multimorbidity: A systematic review and meta-analysis of randomised controlled trials

OBJECTIVES: To investigate the benefits and harms of exercise therapy on physical and psychosocial health in people with multimorbidity. DESIGN: Systematic review of randomised controlled trials (RCTs). Data sources MEDLINE, EMBASE, CENTRAL and CINAHL from 1990 to April 20th, 2020 and Cochrane reviews on the effect of exercise therapy for each of the aforementioned conditions, reference lists of the included studies, the WHO registry and citation tracking on included studies in Web of Science. ELIGIBILITY CRITERIA FOR STUDY SELECTION: RCTs investigating the benefit of exercise therapy in people with multi-morbidity, defined as two or more of the following conditions: osteoarthritis (of the knee or hip), hypertension, type 2 diabetes, depression, heart failure, ischemic heart disease, and chronic obstructive pulmonary disease on at least one of the following outcomes: Health-related quality of life (HRQoL), physical function, depression or anxiety. SUMMARY AND QUALITY OF THE EVIDENCE: Meta-analyses using a random-effects model to assess the benefit of exercise therapy and the risk of non-serious and serious adverse events according to the Food and Drug Administration definition. Meta-regression analyses to investigate the impact of pre-specified mediators of effect estimates. Cochrane ‘Risk of Bias Tool’ 2.0 and the GRADE assessment to evaluate the overall quality of evidence. RESULTS: Twenty-three RCTs with 3363 people, testing an exercise therapy intervention (mean duration 13.0 weeks, SD 4.0) showed that exercise therapy improved HRQoL (standardised mean difference (SMD) 0.37, 95 % CI 0.14 to 0.61) and objectively measured physical function (SMD 0.33, 95 % CI 0.17 to 0.49), and reduced depression symptoms (SMD -0.80, 95 % CI -1.21 to -0.40) and anxiety symptoms (SMD -0.49, 95 % CI -0.99 to 0.01). Exercise therapy was not associated with an increased risk of non-serious adverse events (risk ratio 0.96, 95 % CI 0.53-1.76). By contrast, exercise therapy was associated with a reduced risk of serious adverse events (risk ratio 0.62, 95 % CI 0.49 to 0.78). Meta-regression showed that increasing age was associated with lower effect sizes for HRQoL and greater baseline depression severity was associated with greater reduction of depression symptoms. The overall quality of evidence for all the outcomes was downgraded to low, mainly due to risk of bias, inconsistency and indirectness. CONCLUSIONS: Exercise therapy appears to be safe and to have a beneficial effect on physical and psychosocial health in people with multimorbidity. Although the evidence supporting this was of low quality, it highlights the potential of exercise therapy in the management and care of this population.