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Effects of adding exercise to usual care in patients with either hypertension, type 2 diabetes or cardiovascular disease: a systematic review with meta-analysis and trial sequential analysis
  1. Anupa Rijal1,2,
  2. Emil Eik Nielsen1,2,
  3. Tara Ballav Adhikari3,
  4. Sarmila Dhakal4,
  5. Mathias Maagaard5,
  6. Reza Piri6,7,
  7. Dinesh Neupane8,
  8. Peter Haulund Gæde1,
  9. Michael Hecht Olsen1,2,
  10. Janus Christian Jakobsen1,9
  1. 1 Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
  2. 2 Department of Internal Medicine, Holbaek Hospital, Holbaek, Denmark
  3. 3 Department of Public Health, Section for Global Health, Aarhus University, Aarhus, Denmark
  4. 4 Unit for Health Promotion Research, University of Southern Denmark, Odense, Denmark
  5. 5 Centre for Anaesthesiological Research, Department of Anaesthesiology, Zealand University Hospital, Koge, Denmark
  6. 6 Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
  7. 7 Department of Clinical Research, University of Southern Denmark, Odense, Denmark
  8. 8 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
  9. 9 Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
  1. Correspondence to Anupa Rijal, Department of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark; anuparijal{at}


Objective To assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease.

Design Systematic review with meta-analysis and trial sequential analysis of randomised clinical trials.

Data sources The CENTRAL, MEDLINE, EMBASE, Science Citation Index Expanded on Web of Science and BIOSIS searched from inception to July 2020.

Eligibility criteria for selecting studies We included all randomised clinical trials adding any form of trialist defined exercise to usual care versus usual care in participants with either hypertension, type 2 diabetes or cardiovascular disease irrespective of setting, publication status, year and language.

Outcome and measures The primary outcomes were all-cause mortality, serious adverse events and quality of life.

Data extraction and synthesis Five independent reviewers extracted data and assessed risk of bias in pairs. Our methodology was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Grading of Recommendations Assessment, Development and Evaluation and Cochrane Risk of Bias-version 1.

Results We included 950 trials, of which 248 trials randomising 21 633 participants reported on our predefined outcomes. All included trials were at high risk of bias. The major types of exercise reported were dynamic aerobic exercise (126/248 trials), dynamic resistance exercise (25/248 trials), and combined aerobic and resistance exercise (58/248 trials). The study participants were included due to cardiovascular diseases (189/248 trials), type 2 diabetes (41/248 trials) or hypertension (16/248 trials). The median intervention period was 3 months (IQR: 2–4 months) and the median follow-up period was 6 months (IQR: 3–8 months) after randomisation. Meta-analyses and trial sequential analyses showed evidence of a beneficial effect of adding exercise to usual care when assessing all-cause mortality (risk ratio (RR) 0.82; 95% CI 0.73 to 0.93; I2=0%, moderate certainty of evidence) and serious adverse events (RR 0.79; 95% CI 0.71 to 0.88; I2=0%, moderate certainty of evidence). We did not find evidence of a difference between trials from different economic regions, type of participants, type of exercise or duration of follow-up. Quality of life was assessed using several different tools, but the results generally showed that exercise improved quality of life, but the effect sizes were below our predefined minimal important difference.

Conclusions A short duration of any type of exercise seems to reduce the risk of all-cause mortality and serious adverse events in patients with either hypertension, type 2 diabetes or cardiovascular diseases. Exercise seems to have statistically significant effects on quality of life, but the effect sizes seem minimal.

PROSPERO registration number CRD42019142313.

  • Meta-analysis
  • Exercise
  • Cardiovascular Diseases
  • Randomized Controlled Trial
  • Noncommunicable Diseases

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  • Twitter @anuparijal, @NepalChirp

  • Contributors AR, MHO and JCJ conceived this systematic review. AR, TBA and SD conducted the literature search. AR, TBA, SD, MM and RP extracted data independently and assessed the risk of bias using the Cochrane Risk of Bias-version 1 (RoB1) in pairs. AR conducted the data analysis and data interpretation aided by EEN and JCJ. AR wrote the first draft with input from EEN, MHO and JCJ. DN, PHG provided valuable comments and amended the article. All authors read, amended and approved the final manuscript.

  • Funding The salary of the first author was supported by a research grant from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation, grant number NNF17SA0031406.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.