Tamoxifen effects on endothelial function and cardiovascular risk factors in men with advanced atherosclerosis

Background-Tamoxifen and its analogues act as selective estrogen receptor m odulators (SERMs) in women, with estrogen-like activities on some plasma ca rdiovascular risk factors leg, lipoproteins). Effects of SERMs on men with coronary artery disease (CAD) have not been reported. Methods and Results-Thirty-one men with angiographically proven CAD were re cruited; 16 were treated with tamoxifen (40 mg/d) for 56 days, and 15 were untreated. All the CAD patients were medicated with aspirin and an HMG-CoA reductase inhibitor for greater than or equal to6 weeks before entering the study. Ten men with angina-like symptoms but normal coronary arteries by a ngiography (NCA group) were also treated with tamoxifen. Blood samples were collected at days -7, 0, 7, 14, 21, 28, and 56 of treatment. Endothelium-d ependent flow-mediated dilatation (ED-FMD) of the brachial artery was measu red by high-resolution ultrasound at 5 visits. Tamoxifen caused an increase in %ED-FMD maximal at 28 days in the CAD group (2.1 +/- 0.3% to 7.5 +/- 0. 7%; P<0,0001) and the NCA group (3.8 <plus/minus> 0.4% to 7.9 +/- 1.0%; P<0 .0001), with no significant change in the untreated group. Tamoxifen also c aused decreases in several plasma cardiovascular risk factors, including to tal cholesterol, triglycerides, lipoprotein(a), and fibrinogen. Except for the triglyceride response, these effects were similar to those reported for postmenopausal women treated with tamoxifen. Conclusions-Tamoxifen substantially increased ED-FMD in men with CAD who we re taking conventional medication. Together with the effects on risk factor s, the data strongly support clinical evaluation of SERMs for the treatment of men with CAD.