Raloxifene reduces risk of vertebral fractures and breast cancer in postmenopausal women regardless of prior hormone therapy
TABLE 1
Absolute and relative risks of new vertebral fractures with raloxifene 60 mg/d compared with placeboa
| Women who had used HT (n=1305) | Women who had notused HT (n=3232) | Overall study population d | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Placebo (n=654) | Raloxifene 60 mg/d(n=651) | RR (95% CI)b [ARR] | Placebo (n=1634) | Raloxifene 60 md/d (n=1598) | RR (95% CI)[ARR] | Interaction P-valuec | RR (95% CI) | ||
| Women with prevalent fractures | 25.36% | 13.68% | 0.54(0.36–0.81)[11.68%] | 24.24% | 17.11% | 0.71(0.57–0.88)[7.13%] | .27 | 0.66(0.55–0.81) | |
| Women without prevalent vertebral | 6.29% | 1.82% | 0.29(0.13–0.63) [4.47%] | 5.54% | 3.46% | 0.62(0.41–0.95)[2.08%] | .09 | 0.51(0.35–0.73) | |
| a Results with raloxifene 60 mg/d are shown since this is the clinically approved dose for osteoporosis prevention and treatment. Results with pooled raloxifene doses were similar. Data from women with at least one post-baseline follow-up spinal radiograph were included in this table. | |||||||||
| b RR (95% CI) denotes relative risk (95% confidence interval) Absolute risk reductions, denoted [ARR], are the differences between the placebo and raloxifene groups. Similar results were observed with raloxifene (pooled 60 mg/d and 120 mg/d doses) on vertebral fracture risk, in women who previously used HT [ARR=6.6%; RR=0.47 (95% CI, 0.35–0.63)], and in women without prior HT use [ARR=4.4%; RR=0.66 (95% CI, 0.55–0.78); interaction P=.06] | |||||||||
| c Results for the overall study population would be used unless the interaction effects between therapy group and prior HT use were statistically significant (P<.10), in which case, the results in the subgroups of women with and women without prior HT use should be used. | |||||||||
| d Delmas et al10 published the results for the overall study population, regardless of whether or not information on the participants’ HT use was available. | |||||||||
FIGURE
Percentage of women with and without prior HT use who experienced new vertebral fractures in the 4-year MORE study
This analysis included all women with at least 1 post-baseline follow-up vertebral radiograph, who reported their status of prior HT use. The relative risks (RR) and 95% confidence intervals (CI) are shown for women treated with either placebo or raloxifene 60 mg/d. The absolute risk reductions were 6.7% in women with prior HT use and 3.7% in women without prior HT use. The interaction P-value was .05.
Cardiovascular events
In women with and without prior HT use, treatment with raloxifene (pooled doses) did not result in statistically significant changes in the incidence of new cardiovascular, coronary, or cerebrovascu-lar events, compared with placebo ( Table2 ). In a subgroup of women who were at high risk of cardiovascular disease,15 prior HT use had no effect on the incidence of new cardiovascular events with raloxifene (pooled doses) treatment ( Table 2 ). The interaction P-values remained similar after adjusting for the baseline cardiovascular risk factors (Table W1, at www.jfponline.com) that were significantly different between women with and without prior HT use.
TABLE 2
Absolute and relative risks of cardiovascular events with raloxifene (pooled doses) compared with placeboa
| Women who had used HT (n=2235) | Women who had not used HT (n=5447) | Overall studypopulation | ||||||
|---|---|---|---|---|---|---|---|---|
| Placebo(n=738) | Pooled raloxifene(n=1497) | RR (95% CI)b [ARR] | Placebo (n=1833) | Pooled raloxifene (n=3614) | RR(95% CI)[ARR] | Interaction P-valuec | RR(95% CI) | |
| Cardiovascular events | 2.71% | 2.87% | 1.06(0.63–1.79)[–0.16%] | 4.15% | 3.68% | 0.89(0.67–1.17) [0.47%] | .56 | 0.92(0.72–1.18) |
| Coronary events | 1.49% | 1.74% | 1.17 (0.58–2.35)[–0.25%] | 2.40% | 2.08% | 0.87 (0.60–1.25) [0.32%] | .46 | 0.92(0.67–1.28) |
| Cerebrovascularevents | 1.22% | 1.14% | 0.93(0.42–2.08)[0.08%] | 1.75% | 1.63% | 0.94 (0.61–1.43)[.012%] | .99 | 0.93(0.64–1.36) |
| Cardiovascularevents in high-risk subgroupd | 12.66% | 5.91% | .047(0.21–1.06)[6.75%] | 13.08% | 8.54% | 0.65 (0.42–1.01)[4.54%] | .49 | 0.60(0.41–0.88) [4.54%] |
| a Pooled raloxifene doses were used in this analysis, since there were few events. There were no differences in the incidence of events between the raloxifene doses. | ||||||||
| b Relative risk (RR), 95% confidence interval (95% CI). Absolute risk reductions, denoted [ARR], are the differences between the placebo and raloxifene groups. | ||||||||
| c The interaction effects between therapy group and prior HT use were not statistically significant (P>.10), so results from the overall study population would be used. Barrett-Connor et al14 reported the results for raloxifene 60 mg/d and raloxifene 120 mg/d in the overall study population, regardless of whether or not information on the participants’ HT use was available. | ||||||||
| d Of the 1029 women in the high-risk subgroup, 764 women had no prior history of HT use (placebo, n=237; raloxifene, n=527), and 265 women reported prior HT use (placebo, n=79; raloxifene, n=186). | ||||||||
Breast cancer
In women with and without prior HT use, similar reductions in the incidence of breast cancer (regardless of invasiveness), invasive breast cancer, and estrogen-receptor positive invasive breast cancer, were observed after raloxifene treatment (pooled doses) compared with placebo ( Table 3 ). The interaction P-values remained similar after adjusting for the baseline breast cancer risk factors (Table W1) that were significantly different between women with and without prior HT use.
TABLE 3
Absolute and relative risks of breast cancer with raloxifene (pooled doses) compared with placeboa
| Women who had used HT (n=2235) | Women who had notused HT (n=5447) | Overall study population | ||||||
|---|---|---|---|---|---|---|---|---|
| Placebo(n=738) | Pooledraloxifene(n=1497) | RR(95% CI)b [ARR] | Placebo(n=1833) | Pooled raloxifene(n=3614) | RR(95% CI)[ARR] | InteractionP-valuec | RR(95% CI) | |
| Breast cancer d | 2.30% | 0.73% | 0.32(0.15–0.68)[1.57%] | 1.47% | 0.64% | 0.43(0.25–0.75)[0.83%] | .52 | 0.38 (0.24–0.58) |
| Invasivebreast cancer | 2.03% | 0.47% | 0.23(0.09–0.56)[1.56%] | 1.25% | 0.39% | 0.31(0.16–0.60) [0.86%] | .60 | 0.28(0.17–0.46) |
| Invasiveestrogen-receptorpositive breastcancer | 1.76% | 0.27% | 0.15(0.05–0.46)[1.49%] | 0.87% | 0.17% | 0.19(0.08–0.49)[0.70%] | .75 | 0.16(0.09–0.30) |
| a Pooled raloxifene doses were used in this analysis, since there were few events. There were no differences in the incidence of events between the raloxifene doses. | ||||||||
| b Relative risk (RR), 95% confidence interval (95% CI). Absolute risk reductions, denoted [ARR], are the differences between the placebo and raloxifene groups. | ||||||||
| c The interaction effects between therapy group and prior HT use were not statistically significant (P>.10), so results from the overall study population would be used. Cauley et al16 reported the results for in the overall study population, regardless of whether or not information on the participants’ HT use was available. | ||||||||
| d All breast cancer, regardless of invasiveness. | ||||||||
