Vitamin C and atrial fibrillation and ICU

by Harri Hemila


Department of Public Health
University of Helsinki, Finland
harri.hemila@helsinki.fi
http://www.mv.helsinki.fi/home/hemila
Oct 30, 2020


Meta-analyses and a re-analysis


Hemilä H, Chalker E.
Reanalysis of the Effect of Vitamin C on Mortality in the CITRIS-ALI Trial: Important Findings Dismissed in the Trial Report.
Front Med (Lausanne). 2020

https://doi.org/10.3389/fmed.2020.590853
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7575729


Hemilä H, Chalker E
Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis
J Intensive Care 2020
https://doi.org/10.1186/s40560-020-0432-y
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7006137


Hemilä H, Chalker E.
Vitamin C Can Shorten the Length of Stay in the ICU: A Meta-Analysis.
Nutrients 2019
https://doi.org/10.3390/nu11040708
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521194
https://www.ncbi.nlm.nih.gov/pubmed/30934660

Hemilä H, Suonsyrjä T.
Vitamin C for preventing atrial fibrillation in high risk patients: a systematic review and meta-analysis.
BMC Cardiovascular Disorders 2017;17:49
https://doi.org/10.1186/s12872-017-0478-5
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286679


An early version of the above text was prepared for a Cochrane review
Hemilä H, Suonsyrjä T.
Vitamin C for treating atrial fibrillation
http://www.mv.helsinki.fi/home/hemila/H/2015_vitC_AF_draft.pdf
That version was rejected with a statement:
"Reason for withdrawal from publication: The CRG withdrew this protocol as the current author team is unable to progress to the final stage of the review. The editors consider this title as low priority for the current portfolio of the Heart Group and therefore this title is not open to a new author team."
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011471.pub2/abstract

Thus, our Cochrane review draft found a 45% decrease (95% CI 33% - 56%) in post-operative AF in 8 non-US studies (Analysis 1.2, page 57 of the draft), yet such a finding has low priority in Cochrane Collaboration.

The actual reasons for rejection were not described, see the final reviewer comments and our responses:
http://www.mv.helsinki.fi/home/hemila/H/vitC_AF_1308_reviewer_comments.pdf

See the protocol on which the review was based:
http://www.mv.helsinki.fi/home/hemila/H/HH_2015_CochAF_Protocol.pdf


Hemilä H.
Publication bias in meta-analysis of ascorbic acid for postoperative atrial fibrillation.
American Journal for Health System Pharmacy 2017;74(6):372-373.
https://doi.org/10.2146/ajhp160999
http://www.mv.helsinki.fi/home/hemila/H/2017_L_AJHP.pdf


Letters

Hemilä H
Misleading editorial on vitamin C in JAMA
https://pubpeer.com/publications/07DCB1F79D50182367BF913CC69004#1

Hemilä H
Biased editorial on vitamin C in JAMA
https://pubpeer.com/publications/6C1E79E2B8EA7E2DEED9B46C2B717C#1


Hemilä H
Misleading statistical analysis of the CITRIS-ALI trial on vitamin C and sepsis

https://pubpeer.com/publications/922E178C147621E5F20C6C0561738B#2


Hemilä H, Chalker E.
Vitamin C for Cardiac Surgery Patients: Several Errors in a Published Meta-Analysis.
Comment on “Effects of Vitamin C on Organ Function in Cardiac Surgery Patients:
A Systematic Review and Meta-Analysis. Nutrients 2019, 11, 2103”.
Nutrients 2020
https://www.mdpi.com/2072-6643/12/2/586/htm
See the Supplementary file for more details
https://www.mdpi.com/2072-6643/12/2/586/s1

Hemilä H.
Random-Effects Assumption in Meta-analyses.
JAMA. 2019
https://doi.org/10.1001/jama.2019.5439
https://www.ncbi.nlm.nih.gov/pubmed/31265091

Hemilä H.
Errors in a meta-analysis on vitamin C and post-operative atrial fibrillation.
Int J Surg. 2019
https://doi.org/10.1016/j.ijsu.2019.01.025
https://www.ncbi.nlm.nih.gov/pubmed/30831247

Hemilä H.
Erroneus calculation of sample size in a vitamin C and atrial fibrillation trial.
Journal of Cardiology 2017;69(6):895.
https://doi.org/10.1016/j.jjcc.2016.10.010
https://helda.helsinki.fi/handle/10138/228075

Hemilä H.
Vitamin C prevents AF on the basis of four studies
Heart eLetter 5 Feb 2013
http://heart.bmj.com/content/early/2012/08/14/heartjnl-2012-302328.responses#vitamin-c-prevents-af-on-the-basis-of-four-studies


Analyses on vitamin C and cardiac disorders by other authors

These meta-analyses have some shortcomings but the shortcomings do no invalidate the conclusion that there is strong evidence that vitamin C has effects on AF. Thereby these meta-analyses are consistent with the conclusions of the meta-analysis by Hemilä and Suonsyrjä (2017).


Hill et al. (2019)
Effects of Vitamin C on Organ Function in Cardiac Surgery Patients: A Systematic Review and Meta-Analysis. Nutrients 2019

Comments by Harri Hemilä

Hemilä H, Chalker E. Vitamin C for Cardiac Surgery Patients: Several Errors in a Published Meta-Analysis. Comment on “Effects of Vitamin C on Organ Function in Cardiac Surgery Patients: A Systematic Review and Meta-Analysis. Nutrients 2019, 11, 2103”.  Nutrients 2020
https://www.mdpi.com/2072-6643/12/2/586/htm
See the Supplementary file for more details
https://www.mdpi.com/2072-6643/12/2/586/s1



Hill A et al. (2018)
Vitamin C to improve organ dysfunction in cardiac surgery patients-review and pragmatic approach.
Nutrients 2018, 10, 974.
https://www.mdpi.com/2072-6643/10/8/974
Comments by Harri Hemilä
https://pubpeer.com/publications/DEBED5D9F498A0C940E18841C25C75


Shi R et al. (2018)
Sole and combined vitamin C supplementation can prevent postoperative atrial fibrillation after cardiac surgery: A systematic review and meta-analysis of randomized controlled trials.
https://www.ncbi.nlm.nih.gov/pubmed/29603289
Comments by Harri Hemilä
Hemilä H. Random-Effects Assumption in Meta-analyses. JAMA. 2019
https://doi.org/10.1001/jama.2019.5439
https://www.ncbi.nlm.nih.gov/pubmed/31265091



Hu et al. (2017)
Efficacy and safety of vitamin C for atrial fibrillation after cardiac surgery: A meta-analysis with trial sequential analysis of randomized controlled trials.
https://www.ncbi.nlm.nih.gov/pubmed/27956113
Comments by Harri Hemilä
Hemilä H. Errors in a meta-analysis on vitamin C and post-operative atrial fibrillation. Int J Surg. 2019
https://doi.org/10.1016/j.ijsu.2019.01.025
https://www.ncbi.nlm.nih.gov/pubmed/30831247


Baker and Coleman (2016)
Meta-analysis of ascorbic acid for prevention of postoperative atrial fibrillation after cardiac surgery.
https://www.ncbi.nlm.nih.gov/pubmed/27806938
Comments by Harri Hemilä
https://doi.org/10.2146/ajhp160999


Polymeropoulos et al. (2016)
Vitamin C for the Prevention of Postoperative Atrial Fibrillation after Cardiac Surgery: A Meta-Analysis.
https://www.ncbi.nlm.nih.gov/pubmed/27478787
Comments by Harri Hemilä
https://pubpeer.com/publications/612482BB315F0295CADCF91BC11C0B


Meta-analyses on antioxidants in general and AF

Violi et al. (2014)
Antioxidants for prevention of atrial fibrillation: a potentially useful future therapeutic approach? A review of the literature and meta-analysis
https://www.ncbi.nlm.nih.gov/pubmed/24706090

Ali-Hassan-Sayegh et al. (2014)
Antioxidant supplementations for prevention of atrial fibrillation after cardiac surgery: an updated comprehensive systematic review and meta-analysis of 23 randomized controlled trials.
https://www.ncbi.nlm.nih.gov/pubmed/24556447

Harling et al. (2011)
Do antioxidant vitamins have an anti-arrhythmic effect following cardiac surgery? A meta-analysis of randomised controlled trials
https://www.ncbi.nlm.nih.gov/pubmed/21865202