Estrogen Replacement to Reduce Risk of Neurologic Injury After Coronary Artery Bypass Graft Surgery

BACKGROUND:

Women undergoing CABG surgery have a higher operative mortality rate, longer
hospitalizations, and higher hospital costs compared with men. A large proportion of this
excess morbidity and mortality of surgery for women is due to perioperative neurologic
injury. Estrogen has 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.

DESIGN NARRATIVE:

This randomized, placebo controlled study 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 17 beta-estradiol or placebo in a double-blind fashion
beginning the day before surgery and continuing for 5 days after surgery. Patients will be
assessed for neurocognitive dysfunction, which is the most common manifestation of
neurologic injury from cardiac surgery. Neurocognitive testing will be performed 1 to 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
17 beta- estradiol compared with placebo perioperatively. The trial will also evaluate the
importance of postoperative cognitive decline on measures of cognitive function and quality
of life 6 months after surgery, and whether perioperative 17 beta-estradiol treatment
improves these outcomes.

Inclusion Criteria:

- Patients whose scheduled procedure is CABG surgery OR

- Patients whose scheduled procedure is isolated aortic surgery OR

- Patients whose scheduled procedure is mitral valve surgery OR

- Patients whose scheduled procedure is CABG combined with aortic or mitral valve
surgery

Exclusion Criteria:

- Patients having re-operations

- Patients having combined carotid endarterectomy with CABG surgery

- Patients having CABG with tricuspid valve surgery

- Patients having mitral and aortic valvular surgery (with or without CABG surgery)

- Elevation of liver function test before surgery or creatinine before surgery greater
than 2 mg/dl

- Emergency surgery

- Severe cognitive impairment before surgery as indicated by clinical history and/or a
score greater than 12 on the Short Blessed Dementia Screening Test (see d11)

- Inability to attend outpatient visits

- A history of venous thromboembolism

- Unexplained vaginal bleeding

- A history of breast cancer or personal history of endometrial cancer in the absence
of hysterectomy

- Estrogen use within 6 months of the surgery

- Patient refusal to participate

- Inability to speak and read English or visual impairment