Validity: Most studies reported appropriate randomisation procedures (two failed to report the method of randomisation). Most studies were double blinded (one was open label and one did not report blinding). All but one trial used intention-to-treat analysis.
Nine RCTs (n=27,202) and one meta-analysis (n=3,674) were included in the review. The meta-analysis was based on three of the nine included trials.
Aromatase inhibitors alone versus tamoxifen alone: Two trials found beneficial effects on disease-free survival, time to recurrence and time to distant recurrence, but not on overall survival.
Aromatase inhibitors after tamoxifen versus tamoxifen alone: Four trials each found beneficial effects on disease-free survival, but not on overall survival.
Aromatase inhibitors after five years of tamoxifen: Three trials found that aromatase inhibitors improved disease free survival, though in two of these trials the significance was borderline. Based on results from two of the three trials, aromatase inhibitors did not affect overall survival.
Side effects of aromatase inhibitors: The rates of cardiovascular, cerebrovascular and thromboembolic events were generally similar between the aromatase inhibitor and tamoxifen groups in six studies; aromatase inhibitors were associated with higher levels of fractures and osteoporosis and lower levels of gynaecological toxicities (including endometrial cancer) compared to tamoxifen.