TABLE 2.
Primary and secondary endpoints according to randomization arm1
| Event | Placebo (n = 830) | 1600 IU/day (n = 832) | P value | 3200 IU/day (n = 833) | P value | P value for trend | Combined Vitamin D Arms vs. Placebo | P value |
|---|---|---|---|---|---|---|---|---|
| PY, n | 3480.0 | 3558.2 | 3538.4 | — | ||||
| Primary endpoint: major cardiovascular event2 | ||||||||
| Events, n | 41 | 42 | 36 | — | ||||
| Rate per 100 PY (95% CI) | 1.18 (0.87–1.60) | 1.18 (0.87–1.59) | 1.02 (0.74–1.41) | — | ||||
| HR (95% CI) | 1 | 0.97 (0.63–1.49) | 0.89 | 0.84 (0.54–1.31) | 0.44 | 0.53 | 0.90 (0.62–1.32) | 0.60 |
| Expanded major cardiovascular event endpoint3 | ||||||||
| Events, n | 43 | 43 | 37 | — | ||||
| Rate per 100 PY (95% CI) | 1.24 (0.92–1.66) | 1.21 (0.90–1.63) | 1.05 (0.76–1.44) | — | ||||
| HR (95% CI) | 1 | 0.95 (0.62–1.44) | 0.80 | 0.82 (0.53–1.27) | 0.37 | 0.46 | 0.88 (0.61–1.28) | 0.51 |
| Myocardial infarction | ||||||||
| Events, n | 18 | 18 | 20 | — | ||||
| Rate per 100 PY (95% CI) | 0.52 (0.33–0.82) | 0.51 (0.32–0.80) | 0.57 (0.37–0.88) | — | ||||
| HR (95% CI) | 1 | 0.92 (0.48–1.77) | 0.80 | 1.04 (0.55–1.96) | 0.92 | 0.78 | 0.98 (0.56–1.71) | 0.94 |
| Stroke | ||||||||
| Events, n | 18 | 20 | 16 | — | ||||
| Rate per 100 PY (95% CI) | 0.52 (0.33–0.82) | 0.56 (0.36–0.87) | 0.45 (0.28–0.74) | — | ||||
| HR (95% CI) | 1 | 1.08 (0.57–2.05) | 0.81 | 0.87 (0.44–1.70) | 0.68 | 0.70 | 0.97 (0.55–1.72) | 0.93 |
| Cardiovascular disease death | ||||||||
| Events, n | 5 | 5 | 4 | — | ||||
| Rate per 100 PY (95% CI) | 0.14 (0.06–0.34) | 0.14 (0.06–0.34) | 0.11 (0.04–0.30) | — | ||||
| HR (95% CI) | 1 | 0.94 (0.27–3.24) | 0.92 | 0.76 (0.20–2.83) | 0.68 | 0.73 | 0.85 (0.28–2.53) | 0.77 |
| Primary endpoint: any invasive cancer | ||||||||
| Events, n | 41 | 48 | 40 | — | ||||
| Rate per 100 PY (95% CI) | 1.18 (0.87–1.60) | 1.35 (1.02–1.79) | 1.13 (0.83–1.54) | — | ||||
| HR (95% CI) | 1 | 1.14 (0.75–1.72) | 0.55 | 0.95 (0.61–1.47) | 0.81 | 0.85 | 1.04 (0.72–1.51) | 0.83 |
| Colorectal cancer | ||||||||
| Events, n | 3 | 4 | 1 | — | ||||
| Rate per 100 PY (95% CI) | 0.09 (0.03–0.27) | 0.11 (0.04–0.30) | 0.03 (0.003–0.20) | — | ||||
| HR (95% CI) | 1 | 1.28 (0.29–5.74) | 0.74 | 0.32 (0.03–3.11) | 0.33 | 0.37 | 0.80 (0.19–3.37) | 0.80 |
| Breast cancer | ||||||||
| Events, n | 6 | 4 | 6 | — | ||||
| Rate per 100 PY (95% CI) | 0.17 (0.08–0.38) | 0.11 (0.04–0.30) | 0.17 (0.08–0.38) | — | ||||
| HR (95% CI) | 1 | 0.69 (0.20–2.45) | 0.57 | 1.08 (0.35–3.35) | 0.90 | 0.92 | 0.88 (0.32–2.43) | 0.81 |
| Prostate cancer | ||||||||
| Events, n | 13 | 11 | 15 | — | ||||
| Rate per 100 PY (95% CI) | 0.37 (0.22–0.64) | 0.31 (0.17–0.56) | 0.42 (0.26–0.70) | — | ||||
| HR (95% CI) | 1 | 0.78 (0.35–1.73) | 0.53 | 1.07 (0.51–2.24) | 0.87 | 0.83 | 0.92 (0.47–1.79) | 0.81 |
| Cancer death | ||||||||
| Events, n | 0 | 0 | 0 | — | ||||
| Death from any cause | ||||||||
| Events, n | 7 | 7 | 5 | — | ||||
| Rate per 100 PY (95% CI) | 0.20 (0.10–0.42) | 0.20 (0.09–0.42) | 0.14 (0.06–0.34) | — | ||||
| HR (95% CI) | 1 | 0.94 (0.33–2.68) | 0.91 | 0.68 (0.22–2.14) | 0.68 | 0.56 | 0.81 (0.32–2.06) | 0.66 |
| Analyses excluding the first 2 years of follow-up | ||||||||
| Major cardiovascular event2 | ||||||||
| Events, n | 24 | 26 | 19 | — | ||||
| Rate per 100 PY (95% CI) | 0.69 (0.46–1.03) | 0.73 (0.50–1.07) | 0.50 (0.34–0.84) | — | ||||
| HR (95% CI) | 1 | 1.02 (0.58–1.77) | 0.95 | 0.76 (0.41–1.38) | 0.36 | 0.42 | 0.89 (0.54–1.46) | 0.64 |
| Any invasive cancer | ||||||||
| Events, n | 20 | 32 | 26 | — | ||||
| Rate per 100 PY (95% CI) | 0.57 (0.37–0.89) | 0.90 (0.64–1.27) | 0.73 (0.50–1.08) | — | ||||
| HR (95% CI) | 1 | 1.53 (0.88–2.68) | 0.13 | 1.26 (0.70–2.25) | 0.44 | 0.45 | 1.40 (0.84–2.32) | 0.33 |
1
Adjusted for age and sex in the Cox proportional hazards regression model. Abbreviation: PY, person-years.
2
Composite endpoint of myocardial infarction, stroke, and cardiovascular disease mortality.
3
Expanded composite endpoint of myocardial infarction, stroke, cardiovascular disease mortality, and coronary revascularization (i.e., coronary artery bypass grafting or percutaneous coronary intervention).