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. 2017 Mar 16;2017(3):CD011114. doi: 10.1002/14651858.CD011114.pub2

Summary of findings for the main comparison. Vitamin C supplementation versus placebo for primary prevention of cardiovascular disease.

Vitamin C supplementation versus placebo for primary prevention of cardiovascular disease
Patient or population: middle‐aged US male physicians
 Settings: Not clear
 Intervention: Vitamin C supplementation
Comparision: placebo
Outcomes Illustrative comparative risks* (95% CI) Relative effect
 (95% CI) No of Participants
 (studies) Quality of the evidence
 (GRADE) Comments
Assumed risk Corresponding risk
Placebo Vitamin C supplementation
Major cardiovascular event 
 Physicians
 Follow‐up: mean 8 years 86 per 1000 85 per 1000 
 (77 to 94) HR 0.99 
 (0.89 to 1.10) 14,641
 (1 study) ⊕⊕⊝⊝
 low1,2 Inconsistency was difficult to evaluate given that one trial assessed the primary outcome. Grey literature search is unlikely to introduce publication bias. See Appendix 2 for major cardiovascular event checklist
Cardiovascular mortality 
 Physicians
 Follow‐up: mean 8 years 35 per 1000 35 per 1000 
 (29 to 42) HR 1.02 
 (0.85 to 1.22) 14,641
 (1 study) ⊕⊝⊝⊝
 very low1,2,3 Inconsistency was difficult to evaluate given that one trial assessed the primary outcome. Grey literature search is unlikely to introduce publication bias. See Appendix 2 for major cardiovascular event checklist
All‐cause mortality 
 Physicians
 Follow‐up: mean 8 years 110 per 1000 117 per 1000 
 (107 to 128) HR 1.07 
 (0.97 to 1.18) 14,641
 (1 study) ⊕⊝⊝⊝
 very low1,2,3 Inconsistency was difficult to evaluate given that one trial assessed the primary outcome. Grey literature search is unlikely to introduce publication bias. See Appendix 2 for major cardiovascular event checklist
Total myocardial infarction (fatal and non‐fatal) 
 Physicians
 Follow‐up: mean 8 years 34 per 1000 36 per 1000 
 (30 to 42) HR 1.04 
 (0.87 to 1.24) 14,641
 (1 study) ⊕⊕⊝⊝
 low1,2 Inconsistency was difficult to evaluate given that one trial assessed the primary outcome. Grey literature search is unlikely to introduce publication bias. See Appendix 2 for major cardiovascular event checklist
Total stroke (fatal and non‐fatal) 
 Physicians
 Follow‐up: mean 8 years 34 per 1000 30 per 1000 
 (25 to 36) HR 0.89 
 (0.74 to 1.07) 14,641
 (1 study) ⊕⊕⊝⊝
 low1,2 Inconsistency was difficult to evaluate given that one trial assessed the primary outcome. Grey literature search is unlikely to introduce publication bias. See Appendix 2 for major cardiovascular event checklist
Self‐reported CABG/PTCA 
 Participant self‐reports
 Follow‐up: mean 8 years 97 per 1000 93 per 1000 
 (84 to 103) HR 0.96 
 (0.86 to 1.07) 14,641
 (1 study) ⊕⊕⊝⊝
 low1,2 Inconsistency was difficult to evaluate given that one trial assessed the primary outcome. Self‐reported outcomes are unlikely to introduce bias in this trial. Grey literature search is unlikely to introduce publication bias. See Appendix 2 for major cardiovascular event checklist
Self‐reported angina 
 Participant self‐reports
 Follow‐up: mean 8 years 105 per 1000 98 per 1000 
 (89 to 108) HR 0.93 
 (0.84 to 1.03) 14,641
 (1 study) ⊕⊕⊝⊝
 low1,2 Inconsistency was difficult to evaluate given that one trial assessed the primary outcome. Self‐reported outcomes are unlikely to introduce bias in this trial. Grey literature search is unlikely to introduce publication bias. See Appendix 2 for major cardiovascular event checklist
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
 CI: Confidence interval; HR: Hazard ratio; CABG: coronary artery bypass grafting; PTCA: percutaneous transluminal coronary angioplasty
GRADE Working Group grades of evidence
 High quality: Further research is very unlikely to change our confidence in the estimate of effect.
 Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
 Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
 Very low quality: We are very uncertain about the estimate.

1 Middle‐aged US male physicians and is therefore not highly applicable to the decision context (downgraded by one for indirectness).
 2 Small number of included studies (n = 1) for these outcomes (downgraded by one for imprecision).
 3 8 years follow‐up (timeframe) may not be sufficient to detect mortality (downgraded by one for indirectness).