Estradiol For Neurocognitive Dysfunction After CABG

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Women undergoing coronary artery bypass graft (CABG) surgery have a higher operative mortality rate, longer hospitalizations, and higher hospital cost compared with men. A large proportion of this excess morbidity and mortality of surgery for women is due to perioperative neurologic injury. Estrogens have been consistently shown to reduce the extent of neurologic injury in a variety of in vitro and animal experimental stroke models. These data together strongly suggest that the higher risk for perioperative neurologic complications for elderly women may relate to their estrogen deficient state. In this randomized, placebo controlled study, we will test the hypothesis that perioperative estrogen replacement in postmenopausal women reduces the risk for neurologic injury after CABG surgery. Three hundred thirty four women undergoing CABG surgery will be prospectively randomized to receive either 17beta-estradiol or placebo in a double-blind fashion beginning the day before surgery and continued for 5 days after surgery. Patients will be assessed for neurocognitive dysfunction, the most common manifestation of neurologic injury from cardiac surgery. Neurocognitive testing will be performed 1-2 days before surgery, 4 to 6 weeks postoperatively, and 6- months after surgery. The primary endpoint will be neurocognitive function 4 to 6 weeks after surgery for women who received 17beta- estradiol compared with placebo perioperatively. We will also evaluate for the importance of postoperative cognitive decline on measures of cognitive function and quality of life 6 months after surgery and whether perioperative 17beta-estradiol treatment improves these latter outcomes. The results of this study will evaluate the efficacy and safety of an easily implemented therapy for improving neurologic outcome and quality of life after CABG surgery for postmenopausal women.