# Presentation: 730363

## Additional Analyses of Fracture Risk and the Global Index in the WHI Estrogen + Progestin Trial

- Garnet Anderson
- WHI Clinical Coordinating Center
- Fred Hutchinson Cancer Research Center
- October 7, 2003

## Total fracture risk with E+P by prior hormone use

|  | E + P |  | Placebo |  | Hazard | Unwt | Wtd |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  | N | % | N | % | Ratio | Z | Z |
| Overall | 733 | 1.52 | 896 | 1.99 | 0.76 | 6.10 | 6.07 |
| No prior PHT use | 555 | 1.57 | 678 | 2.03 | 0.76 | 5.44 | 5.34 |
| Any prior PHT use | 178 | 1.40 | 218 | 1.87 | 0.75 | 3.20 | 3.27 |

- Not to be reproduced or distributed without permission from WHI

## Total fracture incidence by prior PHT use and randomization assignment

- Not to be reproduced or distributed without permission from WHI

## Sensitivity Analysis of total fracture risk with E+P by prior hormone use—“per protocol” 

|  | E + P |  | Placebo |  | Hazard | Unwt | Wtd |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  | N | % | N | % | Ratio | Z | Z |
| Overall | 400 | 0.92 | 626 | 1.39 | 0.72 | 5.65 | 5.77 |
| No prior PHT use | 328 | 0.93 | 475 | 1.42 | 0.72 | 5.28 | 5.25 |
| Any prior PHT use | 112 | 0.88 | 151 | 1.29 | 0.74 | 3.22 | 3.40 |

- Not to be reproduced or distributed without permission from WHI

## Total fracture risk with E+P by prior hormone use and BMI

|  | E + P |  | Placebo |  | Hazard | Unwt | Wtd |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  | N | % | N | % | Ratio | Z | Z |
| No prior PHT use/ BMI < 30 | 356 | 1.58 | 463 | 2.16 | 0.72 | 4.85 | 4.46 |
| No prior PHT use/ BMI 30 + | 194 | 1.53 | 211 | 1.80 | 0.82 | 3.52 | 3.80 |
| Prior PHT use / BMI < 30 | 126 | 1.38 | 157 | 1.89 | 0.72 | 2.85 | 3.11 |
| Prior PHT use /  BMI 30+ | 52 | 1.46 | 59 | 1.76 | 0.84 | 1.47 | 1.33 |

- P = 0.71 for test of interaction

- Not to be reproduced or distributed without permission from WHI

## BMI < 30

- BMI 30+

- Unweighted p = .71

- No prior hormone use

- No prior hormone use

- Total Fractures

- Not to be reproduced or distributed without permission from WHI

## Global index comparisons by age at screening

|  | E+P |  | Placebo |  |  | Hazard | P for  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  | N | % |  | N | % | Ratio | interaction |
| Overall | 854 | 1.78 |  | 723 | 1.60 | 1.12 |  |
| Age at screening |  |  |  |  |  |  |  |
| 50-54 | 49 | 0.77 |  | 41 | 0.70 | 1.12 |   |
| 55-59 | 115 | 1.10 |  | 97 | 0.99 | 1.08 |   |
| 60-64 | 177 | 1.61 |  | 121 | 1.22 | 1.33 | .99 |
| 65-69 | 207 | 1.97 |  | 198 | 1.96 | 1.01 |  |
| 70-74 | 182 | 2.70 |  | 175 | 2.64 | 1.02 |  |
| 75-59 | 124 | 4.15 |  | 91 | 3.35 | 1.24 |  |

- Not to be reproduced or distributed without permission from WHI

## Global index comparisons by BMI

|  | E+P |  | Placebo |  |  | Hazard | P for  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  | N | % |  | N | % | Ratio | interaction |
| Body Mass Index |  |  |  |  |  |  |  |
| < 25 | 243 | 1.66 |  | 201 | 1.45 | 1.16 |   |
| 25-29 | 290 | 1.71 |  | 248 | 1.56 | 1.12 | .62  |
| 30+ | 318 | 1.95 |  | 269 | 1.78 | 1.08 |  |

- Not to be reproduced or distributed without permission from WHI

## Global index comparisons by fracture history and smoking status

|  | E+P |  | Placebo |  |  | Hazard | P for  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  | N | % |  | N | % | Ratio | interaction |
| History of fracture after age 55 |  |  |  |  |  |  | .50 |
|    No | 546 | 1.67 |  | 475 | 1.47 | 1.15 |   |
|    Yes | 133 | 2.42 |  | 127 | 2.33 | 1.04 |   |
| Smoking Status |  |  |  |  |  |  | .76 |
|    Never/past smoker | 729 | 1.71 |  | 613 | 1.54 | 1.12 |  |
|    Current smoker | 118 | 2.40 |  | 93 | 1.99 | 1.18 |  |

- Not to be reproduced or distributed without permission from WHI

## Treatment arm comparisons in the post-intervention period (7/8/02 – 8/31/03)

|  | E+P |  | Placebo |  |  | Hazard |  | Unwtd |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  | N | % |  | N | % |  | Ratio | Z |
| Hip fracture | 13 | 0.19 |  | 17 | 0.26 |  | 0.74 | 1.06 |
| Vertebral fracture | 8 | 0.12 |  | 14 | 0.22 |  | 0.55 | 1.64 |
| Other fracture | 70 | 1.11 |  | 75 | 1.27 |  | 0.88 | 1.20 |
| Total fracture | 90 | 1.32 |  | 105 | 1.60 |  | 0.83 | 1.49 |
| Global index | 166 | 2.43 |  | 136 | 2.07 |  | 1.18 | -3.16 |

- Not to be reproduced or distributed without permission from WHI

## Cumulative treatment arm comparisons (Randomization through – 8/31/03)

|  | E+P |  | Placebo |  |  | Hazard |  | Unwtd | Wtd |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  | N | % |  | N | % |  | Ratio | Z | Z |
| Hip fracture | 66 | 0.12 |  | 92 | 0.18 |  | 0.68 | 2.45 | 2.31 |
| Vertebral fracture | 63 | 0.11 |  | 92 | 0.18 |  | 0.66 | 2.67 | 2.32 |
| Other fracture | 719 | 1.31 |  | 873 | 1.69 |  | 0.76 | 6.06 | 6.19 |
| Total fracture | 827 | 1.50 |  | 995 | 1.92 |  | 0.77 | 6.04 | 5.90 |
| Global index | 1006 | 1.83  |  | 845 | 1.63 |  | 1.14 | -3.56 | -3.25 |

- Not to be reproduced or distributed without permission from WHI