P3729The left atrial appendage closure by surgery-2 randomized trial

Abstract

Abstract Background Since the left atrium appendage (LAA) is the predilection site for clot formation in patients with atrial fibrillation (AF), closure of the LAA during surgery (LAACS) is often performed but not yet demonstrated to protect against stroke. The recent LAACS trial found that LAA closure protected from strokes and silent brain damages on a moderate (n=187) number of patients. However, results based solely on strokes and cerebral transitory ischemic attacks (TIA) was not significant (18% events in the control group compared to 6% in patients where LAA was closed (p=0.07). Furthermore, incomplete closure of the LAA is of concern, with an increased relative risk for stroke (10–25%). Purpose Determine if LAA closure added to planned open heart surgery protects against post-operative major stroke and minor stroke. Methods Adults scheduled for open-heart surgery who sign informed consent will be included regardless of known AF, provided LAA closure is not previously planned. LAACS-2 is an open, parallel, international multi-center study where patients will be randomized to closure of the LAA (with clip or staple), in addition to planned open-heart surgery. The LAA will remain open in the control group. Randomization will be stratified according to ongoing or expected use of anti-coagulant medication following surgery and classified as coronary artery bypass surgery (CABG) alone, mitral valve surgery or other. The primary endpoint is stroke or TIA occurring over at least two years following surgery. Secondary endpoints are: Total mortality and a combination of stroke, TIA or image of recent cerebral infarction in clinical settings demonstrated post-operatively, until the end follow-up. Occurrence of AF during follow-up will be assessed with prolonged (up to several weeks) monitoring with a three-lead compact sensor. Studies on percutaneous coronary intervention and CABG, estimate a 3.7% pooled incidence of stroke in the first three years following coronary by-pass operations. Using these estimates and those from the previous LAACS study (3.2% strokes on patients with closed LAA vs 11.3% in the control group, p=0.07), we estimate that LAA closure can be demonstrated to protect from strokes, with a significance level of 0.05 and a 90% power, including 1200–1400 patients in an event-driven study. Expecting a cross-over of 10–20%, we plan to enroll 2000 adults. According to the a priori power-calculations, the LAACS-2 trial is powered: 1) to determine if randomization to closure of the LAA in conjunction with planned open-heart surgery, protects patients from post-operative clinical strokes; and 2) if there is an increased thrombogenic effect of incomplete closure or excessive pouch, since such harm can be identified by including between 359 and 1455 patients. Perspective If the LAACS procedure in conjunction with planned open-heart surgery protects against future stroke it should be included in future guidelines. Acknowledgement/Funding Innovation Fund Denmark; NovoNordisk Foundation; Ib Mogens Christiansen; Bispebjerg-Frederiksberg Research Fund