• 作者：Merc&#232 ; Roqué ; ^a ; ^b ; ^{mroque@clinic.ub.es} ; Marta Sitges^a ; ^b ; Joan Sala^c ; Victoria Delgado^a ; Manuel Morales^c ; Jaume Marrugat^d ; Joan Vila^d ; Isaac Subirana^d ; Dolors Tà ; ssies^e ; Juan Carlos Reverter^e ; Miriam Castro^a ; Magdalena Duran^f
• 关键词：MSRE ; modulador selectivo del receptor estrogé ; nico ; PAI-1 ; inhibidor del activador del plasminó ; geno tipo 1 ; PAP ; plasmina/antiplasmina ; TAFI ; inhibidor de la fibrinolisis activable por trombina ; VMF ; vasodilatació ; n mediada por flujo
• 刊名：Revista Espa?ola de Cardiolog¨ªa
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：64
• 期：7
• 页码：572-578
• 全文大小：201 K

Introduction and objectives

Modulation of vascular tone is one of the most relevant estrogen effects. A beneficial effect on endothelial function in postmenopausal women has also been proposed for the selective estrogen receptor modulator raloxifene. However, its effects in women with established cardiovascular disease have not been fully elucidated. In addition, recent trials have generated controversy regarding thromboembolic risk with raloxifene use. The aim of the study was to assess the effect of raloxifene on: a) endothelial function and b) coagulation and fibrinolysis pathways.

Methods

The MERCED trial was a prospective, randomized clinical trial. Thirty-three postmenopausal women with ischemic heart disease were enrolled in the study. Raloxifene treatment was administered for a 3-month period, according to a double-blind crossover design. Assessment of vascular function and biologic parameters related to coagulation pathways were conducted at various pre-established time-points.

Results

Flow-mediated dilatation was severely impaired in the study population, and raloxifene had no effect on endothelial function. Treatment with raloxifene was associated to decreased levels of fibrinogen (3.41 [3.11-3.74] vs. 3.69 [3.40-4.00], P < .05); prothrombin fragments F₁₊₂ (0.93 [0.77-1.12] vs. 0.94 [0.78-1.15], P < .05); and plasmin/antiplasmin complexes (211 [166-267] vs. 242 [199-295], P < .01).

Conclusions

The present study provides evidence that in postmenopausal women with demonstrated endothelial dysfunction and ischemic heart disease, mid-term treatment with raloxifene does not affect endothelial function. In the MERCED trial, no increased thrombotic risk was observed, but a decreased thrombotic and fibrinolytic activity was observed with raloxifene. Further studies are required to determine whether thrombotic risk is associated with specific clinical characteristics or subgroups of postmenopausal women with cardiovascular disease.

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