The left atrial appendage closure by surgery 2 trial: statistical analysis plan for a randomized multicenter trial exploring if the closure of the left atrial appendage during open-heart surgery reduces stroke irrespective of patients’ stroke risk and preoperative atrial fibrillation status

go back to reference Murdock DK, Rengel LR, Schlund A, Olson KJ, Kaliebe JW, Johnkoski JA, Riveron FA. Stroke and atrial fibrillation following cardiac surgery. WMJ. 2003;102:26–30.PubMed Murdock DK, Rengel LR, Schlund A, Olson KJ, Kaliebe JW, Johnkoski JA, Riveron FA. Stroke and atrial fibrillation following cardiac surgery. WMJ. 2003;102:26–30.PubMed

go back to reference Kaatz S, Douketis JD, Zhou H, Gage BF, White RH. Risk of stroke after surgery in patients with and without chronic atrial fibrillation. J Thromb Haemost. 2010;8:884–90.CrossRefPubMed Kaatz S, Douketis JD, Zhou H, Gage BF, White RH. Risk of stroke after surgery in patients with and without chronic atrial fibrillation. J Thromb Haemost. 2010;8:884–90.CrossRefPubMed

go back to reference Ahlsson A, Fengsrud E, Bodin L, Englund A. Postoperative atrial fibrillation in patients undergoing aortocoronary bypass surgery carries an eightfold risk of future atrial fibrillation and a doubled cardiovascular mortality. Eur J Cardiothorac Surg. 2010;37:1353–9.CrossRefPubMed Ahlsson A, Fengsrud E, Bodin L, Englund A. Postoperative atrial fibrillation in patients undergoing aortocoronary bypass surgery carries an eightfold risk of future atrial fibrillation and a doubled cardiovascular mortality. Eur J Cardiothorac Surg. 2010;37:1353–9.CrossRefPubMed

go back to reference Pillarisetti J, Patel A, Bommana S, Guda R, Falbe J, Zorn GT, Muehlebach G, Vacek J, Sue Min L, Lakkireddy D. Atrial fibrillation following open heart surgery: long-term incidence and prognosis. J Interv Card Electrophysiol. 2014;39:69–75.CrossRefPubMed Pillarisetti J, Patel A, Bommana S, Guda R, Falbe J, Zorn GT, Muehlebach G, Vacek J, Sue Min L, Lakkireddy D. Atrial fibrillation following open heart surgery: long-term incidence and prognosis. J Interv Card Electrophysiol. 2014;39:69–75.CrossRefPubMed

go back to reference Lee SH, Kang DR, Uhm JS, Shim J, Sung JH, Kim JY, Pak HN, Lee MH, Joung B. New-onset atrial fibrillation predicts long-term newly developed atrial fibrillation after coronary artery bypass graft. Am Heart J. 2014;167:593-600 e1.CrossRefPubMed Lee SH, Kang DR, Uhm JS, Shim J, Sung JH, Kim JY, Pak HN, Lee MH, Joung B. New-onset atrial fibrillation predicts long-term newly developed atrial fibrillation after coronary artery bypass graft. Am Heart J. 2014;167:593-600 e1.CrossRefPubMed

go back to reference Dawson AG, Asopa S, Dunning J. Should patients undergoing cardiac surgery with atrial fibrillation have left atrial appendage exclusion? Interact Cardiovasc Thorac Surg. 2010;10:306–11.CrossRefPubMed Dawson AG, Asopa S, Dunning J. Should patients undergoing cardiac surgery with atrial fibrillation have left atrial appendage exclusion? Interact Cardiovasc Thorac Surg. 2010;10:306–11.CrossRefPubMed

go back to reference Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A, Lau CPP, Fain E, Yang S, Bailleul C, Morillo CA, Carlson M, Themeles E, Kaufman ES, Hohnloser SH, Investigators A, Van GIC, Capucci A, Lau CPP, Fain E, Yang S, Sc M, Bailleul C, Morillo CA, Carlson M, Themeles E, Kaufman ES, Hohnloser SH, Investigators A. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366:120–9.CrossRefPubMed Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A, Lau CPP, Fain E, Yang S, Bailleul C, Morillo CA, Carlson M, Themeles E, Kaufman ES, Hohnloser SH, Investigators A, Van GIC, Capucci A, Lau CPP, Fain E, Yang S, Sc M, Bailleul C, Morillo CA, Carlson M, Themeles E, Kaufman ES, Hohnloser SH, Investigators A. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366:120–9.CrossRefPubMed

go back to reference Gialdini G, Nearing K, Bhave PD, Bonuccelli U, Iadecola C, Healey JS, Kamel H, Corresponding H. Perioperative atrial fibrillation and long-term risk of ischaemic stroke. JAMA. 2014;312:616–22.CrossRefPubMedPubMedCentral Gialdini G, Nearing K, Bhave PD, Bonuccelli U, Iadecola C, Healey JS, Kamel H, Corresponding H. Perioperative atrial fibrillation and long-term risk of ischaemic stroke. JAMA. 2014;312:616–22.CrossRefPubMedPubMedCentral

go back to reference Park-Hansen J, Holme SJV, Irmukhamedov A, Carranza CL, Greve AM, Al-Farra G, Riis RGC, Nilsson B, Clausen JSR, Nørskov AS, Kruuse CR, Rostrup E, Dominguez H. Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study. J Cardiothorac Surg. 2018;13:53.CrossRefPubMedPubMedCentral Park-Hansen J, Holme SJV, Irmukhamedov A, Carranza CL, Greve AM, Al-Farra G, Riis RGC, Nilsson B, Clausen JSR, Nørskov AS, Kruuse CR, Rostrup E, Dominguez H. Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study. J Cardiothorac Surg. 2018;13:53.CrossRefPubMedPubMedCentral

go back to reference Caliskan E, Sahin A, Yilmaz M, Seifert B, Hinzpeter R, Alkadhi H, Cox JL, Holubec T, Reser D, Falk V, Grünenfelder J, Genoni M, Maisano F, Salzberg SP, Emmert MY. Epicardial left atrial appendage AtriClip occlusion reduces the incidence of stroke in patients with atrial fibrillation undergoing cardiac surgery. EP Europace. 2018;20:1–10. Caliskan E, Sahin A, Yilmaz M, Seifert B, Hinzpeter R, Alkadhi H, Cox JL, Holubec T, Reser D, Falk V, Grünenfelder J, Genoni M, Maisano F, Salzberg SP, Emmert MY. Epicardial left atrial appendage AtriClip occlusion reduces the incidence of stroke in patients with atrial fibrillation undergoing cardiac surgery. EP Europace. 2018;20:1–10.

go back to reference Friedman DJ, Piccini JP, Wang T, Zheng J, Malaisrie SC, Holmes DR, Suri RM, Mack MJ, Badhwar V, Jacobs JP, Gaca JG, Chow S-C, Peterson ED, Brennan JM. Association between left atrial appendage occlusion and readmission for thromboembolism among patients with atrial fibrillation undergoing concomitant cardiac surgery. JAMA. 2018;319:365.CrossRefPubMedPubMedCentral Friedman DJ, Piccini JP, Wang T, Zheng J, Malaisrie SC, Holmes DR, Suri RM, Mack MJ, Badhwar V, Jacobs JP, Gaca JG, Chow S-C, Peterson ED, Brennan JM. Association between left atrial appendage occlusion and readmission for thromboembolism among patients with atrial fibrillation undergoing concomitant cardiac surgery. JAMA. 2018;319:365.CrossRefPubMedPubMedCentral

go back to reference Soltesz EG, Dewan KC, Anderson LH, Ferguson MA, Gillinov AM. Improved outcomes in CABG patients with atrial fibrillation associated with surgical left atrial appendage exclusion. J Card Surg. 2021;36:1201–8.CrossRefPubMed Soltesz EG, Dewan KC, Anderson LH, Ferguson MA, Gillinov AM. Improved outcomes in CABG patients with atrial fibrillation associated with surgical left atrial appendage exclusion. J Card Surg. 2021;36:1201–8.CrossRefPubMed

go back to reference Whitlock RP, Belley-Cote EP, Paparella D, Healey JS, Brady K, Sharma M, Reents W, Budera P, Baddour AJ, Fila P, Devereaux PJ, Bogachev-Prokophiev A, Boening A, Teoh KHT, Tagarakis GI, Slaughter MS, Royse AG, McGuinness S, Alings M, Punjabi PP, Mazer CD, Folkeringa RJ, Colli A, Avezum Á, Nakamya J, Balasubramanian K, Vincent J, Voisine P, Lamy A, Yusuf S, Connolly SJ. Left atrial appendage occlusion during cardiac surgery to prevent stroke. N Engl J Med. 2021;384:2081–91.CrossRefPubMed Whitlock RP, Belley-Cote EP, Paparella D, Healey JS, Brady K, Sharma M, Reents W, Budera P, Baddour AJ, Fila P, Devereaux PJ, Bogachev-Prokophiev A, Boening A, Teoh KHT, Tagarakis GI, Slaughter MS, Royse AG, McGuinness S, Alings M, Punjabi PP, Mazer CD, Folkeringa RJ, Colli A, Avezum Á, Nakamya J, Balasubramanian K, Vincent J, Voisine P, Lamy A, Yusuf S, Connolly SJ. Left atrial appendage occlusion during cardiac surgery to prevent stroke. N Engl J Med. 2021;384:2081–91.CrossRefPubMed

go back to reference January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Circulation. 2019;140:e125–51.CrossRefPubMed January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Circulation. 2019;140:e125–51.CrossRefPubMed

go back to reference Hindricks G, Potpara T, Dagres N, Bax JJ, Boriani G, Dan GA, Fauchier L, Kalman JM, Lane DA, Lettino M, Pinto FJ, Thomas GN, Valgimigli M, Van Putte BP, Kirchhof P, Kühne M, Aboyans V, Ahlsson A, Balsam P, Bauersachs J, Benussi S, Brandes A, Braunschweig F, Camm AJ, Capodanno D, Casadei B, Conen D, Crijns HJGM, Delgado V, Dobrev D, Drexel H, Eckardt L, Fitzsimons D, Folliguet T, Gale CP, Gorenek B, Haeusler KG, Heidbuchel H, Iung B, Katus HA, Kotecha D, Landmesser U, Leclercq C, Lewis BS, Mascherbauer J, Merino JL, Merkely B, Mont L, Mueller C, Nagy KV, Oldgren J, Pavlović N, Pedretti RFE, Petersen SE, Piccini JP, Popescu BA, Pürerfellner H, Richter DJ, Roffi M, Rubboli A, Scherr D, Schnabel RB, Simpson IA, Shlyakhto E, Sinner MF, Steffel J, Sousa-Uva M, Suwalski P, Svetlosak M, Touyz RM, Arbelo E, Blomström-Lundqvist C, Castella M, Dilaveris PE, Filippatos G, La Meir M, Lebeau JP, Lip GYH, Neil Thomas G, Van Gelder IC, Watkins CL. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020;42:373–498.CrossRef Hindricks G, Potpara T, Dagres N, Bax JJ, Boriani G, Dan GA, Fauchier L, Kalman JM, Lane DA, Lettino M, Pinto FJ, Thomas GN, Valgimigli M, Van Putte BP, Kirchhof P, Kühne M, Aboyans V, Ahlsson A, Balsam P, Bauersachs J, Benussi S, Brandes A, Braunschweig F, Camm AJ, Capodanno D, Casadei B, Conen D, Crijns HJGM, Delgado V, Dobrev D, Drexel H, Eckardt L, Fitzsimons D, Folliguet T, Gale CP, Gorenek B, Haeusler KG, Heidbuchel H, Iung B, Katus HA, Kotecha D, Landmesser U, Leclercq C, Lewis BS, Mascherbauer J, Merino JL, Merkely B, Mont L, Mueller C, Nagy KV, Oldgren J, Pavlović N, Pedretti RFE, Petersen SE, Piccini JP, Popescu BA, Pürerfellner H, Richter DJ, Roffi M, Rubboli A, Scherr D, Schnabel RB, Simpson IA, Shlyakhto E, Sinner MF, Steffel J, Sousa-Uva M, Suwalski P, Svetlosak M, Touyz RM, Arbelo E, Blomström-Lundqvist C, Castella M, Dilaveris PE, Filippatos G, La Meir M, Lebeau JP, Lip GYH, Neil Thomas G, Van Gelder IC, Watkins CL. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020;42:373–498.CrossRef

go back to reference Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61:755–9.CrossRefPubMed Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61:755–9.CrossRefPubMed

go back to reference Dominguez H, Madsen CV, Westh ON, Pallesen PA, Carranza CL, Irmukhamedov A, Park-Hansen J, Domínguez H, Madsen CV, Westh ONHNH, Pallesen PA, Carrranza CL, Irmukhamedov A, Park-Hansen J. Does left atrial appendage amputation during routine cardiac surgery reduce future atrial fibrillation and stroke? Curr Cardiol Rep. 2018;20:99.CrossRefPubMedPubMedCentral Dominguez H, Madsen CV, Westh ON, Pallesen PA, Carranza CL, Irmukhamedov A, Park-Hansen J, Domínguez H, Madsen CV, Westh ONHNH, Pallesen PA, Carrranza CL, Irmukhamedov A, Park-Hansen J. Does left atrial appendage amputation during routine cardiac surgery reduce future atrial fibrillation and stroke? Curr Cardiol Rep. 2018;20:99.CrossRefPubMedPubMedCentral

go back to reference Horwich P, Buth KJ, Légaré JF. New onset postoperative atrial fibrillation is associated with a long-term risk for stroke and death following cardiac surgery. J Card Surg. 2013;28:8–13.CrossRefPubMed Horwich P, Buth KJ, Légaré JF. New onset postoperative atrial fibrillation is associated with a long-term risk for stroke and death following cardiac surgery. J Card Surg. 2013;28:8–13.CrossRefPubMed

go back to reference Chang M, Lee CW, Ahn JM, Cavalcante R, Sotomi Y, Onuma Y, Han M, Park DW, Kang SJ, Lee SW, Kim YH, Park SW, Serruys PW, Park SJ. Comparison of outcome of coronary artery bypass grafting versus drug-eluting stent implantation for non-ST-elevation acute coronary syndrome. Am J Cardiol. 2017;120:380–6.CrossRefPubMed Chang M, Lee CW, Ahn JM, Cavalcante R, Sotomi Y, Onuma Y, Han M, Park DW, Kang SJ, Lee SW, Kim YH, Park SW, Serruys PW, Park SJ. Comparison of outcome of coronary artery bypass grafting versus drug-eluting stent implantation for non-ST-elevation acute coronary syndrome. Am J Cardiol. 2017;120:380–6.CrossRefPubMed

go back to reference Madsen CL, Park-Hansen J, Irmukhamedov A, Carranza CL, Rafiq S, Lecoq RR, Camino NP, Modrau IS, Hansson EC, Jeppsson A, Hadad R, Moya-Mitjans A, Greve AM, Christensen R, Carstensen HG, Høst NB, Dixen U, Torp-Pedersen C, Køber L, Gögenur I, Truelsen TC, Kruuse C, Sajadieh A, Domínguez H. The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk. Am Heart J. 2023;264:133–42.CrossRefPubMed Madsen CL, Park-Hansen J, Irmukhamedov A, Carranza CL, Rafiq S, Lecoq RR, Camino NP, Modrau IS, Hansson EC, Jeppsson A, Hadad R, Moya-Mitjans A, Greve AM, Christensen R, Carstensen HG, Høst NB, Dixen U, Torp-Pedersen C, Køber L, Gögenur I, Truelsen TC, Kruuse C, Sajadieh A, Domínguez H. The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk. Am Heart J. 2023;264:133–42.CrossRefPubMed

go back to reference Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium. Circulation. 2011;123:2736–47.CrossRefPubMed Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium. Circulation. 2011;123:2736–47.CrossRefPubMed