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

Major cardiovascular event
Physicians
Follow‐up: mean 8 years

HR 0.99
(0.89 to 1.10)

14,641
(1 study)

⊕⊕⊝⊝
low^1,2

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

HR 1.02
(0.85 to 1.22)

14,641
(1 study)

⊕⊝⊝⊝
very low^1,2,3

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

HR 1.07
(0.97 to 1.18)

14,641
(1 study)

⊕⊝⊝⊝
very low^1,2,3

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

HR 1.04
(0.87 to 1.24)

14,641
(1 study)

⊕⊕⊝⊝
low^1,2

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

HR 0.89
(0.74 to 1.07)

14,641
(1 study)

⊕⊕⊝⊝
low^1,2

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

HR 0.96
(0.86 to 1.07)

14,641
(1 study)

⊕⊕⊝⊝
low^1,2

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

HR 0.93
(0.84 to 1.03)

14,641
(1 study)

⊕⊕⊝⊝
low^1,2

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.