A randomised study comparing the effects of anastrozole (A), letrozole (L), exemestane (E) and tamoxifen (T) on coagulation.
Authors: FM McCaig, L Renshaw, L Williams, O Young, J Murray, EJ Macaskill, M McHugh, P Dawson, J Dixon
Journal: Cancer Research (2009)

Abstract Abstract #1132 Background:&amp;#x2028; Aromatase inhibitors (AIs) reduce circulating oestrogens and so should have either no or a positive effect on coagulation . This study compares the effects of the non-steroidal aromatase inhibitors, A and L and the steroidal inactivator, E on coagulation.&amp;#x2028; Patients and Methods:&amp;#x2028; This was an open, randomized pharmacodynamic study. Plasma coagulation factors were measured in 120 postmenopausal women with invasive ER +ve breast cancer. As part of their adjuvant hormone therapy, patients were randomized to receive upfront therapy with either:&amp;#x2028; 16 weeks of A, 16 weeks of L or 16 weeks of E.&amp;#x2028; Fasting blood samples were collected at entry and after 12 and 16 weeks of each drug. AI patients were then switched to T and further samples measured after 8 months on T.&amp;#x2028; Plasminogen activator inhibitor (PAI) antigen, von Willebrand's Factor (vWF) antigen, antithrombin III (AT111), protein C, protein S total, protein S free, activated protein C, resistance (APCR), factor VIII and fibrinogen were measured.&amp;#x2028; Results:&amp;#x2028; Results expressed as % change from baseline.&amp;#x2028; E vs A vs L&amp;#x2028; Protein C. E caused a significant fall compared to A and L (-15.75 (-21.48, -10.02) vs -3.80 (-10.77, 3.16) vs -3.63 (-10.50, 3.25)) respectively. p = 0.008.&amp;#x2028; ATIII. E caused a significant fall from baseline (-8.55 (-13.33, -3.79))&amp;#x2028; Protein S Free. E + A caused a significant increase from baseline (E 6.90 (1.98, 11.82), A 7.36 (1.37, 13.34).&amp;#x2028; Steroidal vs non-steroidal:&amp;#x2028; Protein C. A significantly greater fall was seen with E than A+L (-15.75 (-21.45, -10.05) vs -3.71 (-8.58, 1.15)) p = 0.002.&amp;#x2028; vWF A+L caused a significant increase from baseline (6.52 (0.66, 12.38) but this was not statistically different to E 5.02 (-1.88, 11.91)).&amp;#x2028; ATIII A significant decrease from baseline was seen with A + L, -4.54 (-8.64, -0.43) but no difference from E 8.55 (13.31, -3.70) p=0.21.&amp;#x2028; Protein S Free There was a significant increase from baseline in both groups (A+L: 5.70 (1.47, 9.92), E: 6.90 (1.98, 11.81), but no difference between the groups p=0.72.&amp;#x2028; T effect:&amp;#x2028; AT111 and protein C levels fell significantly on T whereas protein S free increased on T. Prior A, E or L had no significant impact on post-tamoxifen results.&amp;#x2028; Conclusions:&amp;#x2028; No significant differences in any coagulation factors were seen between A and L&amp;#x2028; E caused a significant fall in protein C and ATIII.&amp;#x2028; The non-steroidal AIs caused a significant increase in vWF.&amp;#x2028; T caused a significant fall in protein C and ATIII and a significant increase in protein S free.&amp;#x2028; No AI significantly influenced post-tamoxifen results.&amp;#x2028; These drugs have significant effects on coagulation which helps to explain their clinical effects on thrombotic and thromboembolic disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1132.