Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease.
OBJECTIVE
We sought to assess the effects of raloxifene, a selective estrogen receptor modulator, on arterial physiology and biology in postmenopausal women with coronary artery disease (CAD).


BACKGROUND
Raloxifene improves endothelial function and markers of vascular health in vitro in experimental animals and in healthy postmenopausal women. In women whose arteries are affected by advanced atherosclerosis, however, the vascular effects of estrogen receptor modulation are unknown.


METHODS
We conducted a prospective, randomized, double-blinded, placebo-controlled, crossover trial of raloxifene, 60 mg/day for 8 weeks, in 33 consecutively eligible and consenting postmenopausal women age 50 to 75 years with known CAD. Parameters measured at the beginning and end of each treatment period included brachial artery flow-mediated dilation (FMD), the primary end point, as well as nitroglycerin-induced dilation, peripheral artery tonometry, serum lipoprotein levels, and markers of vascular function, including urinary prostaglandin, serum endothelin-1, and fibrinogen levels.


RESULTS
Baseline FMD was impaired in these women, as expected (2.84 +/- 0.60%), but there was no significant difference between the effect of raloxifene (0.26 +/- 0.66% increase) and placebo (0.01 +/- 0.63% decrease) on this marker of endothelial function (p = 0.82). No significant raloxifene-related effects were observed on derived aortic pressure, pulse pressure, augmentation index, total cholesterol or low- and high-density lipoprotein subfractions, markers of thrombosis, or vasoconstrictor or vasodilator substances.


CONCLUSIONS
In postmenopausal women with treated CAD, selective estrogen receptor modulation with raloxifene does not improve a comprehensive set of parameters examining vascular function and serum lipoprotein levels.
Griffiths
Kaye A
KA
Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
Sader
Mark A
MA
Skilton
Michael R
MR
Harmer
Jason A
JA
Celermajer
David S
DS
D000368:Aged; D015415:Biomarkers; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D011453:Prostaglandins / Q000652:urine; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D015415:Biomarkers; D019332:Endothelin-1; D008074:Lipoproteins; D011453:Prostaglandins; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D005340:Fibrinogen