Pavel Osmancik1, Dalibor Herman2, Petr Neuzil3, Pavel Hala3, Milos Taborsky4, Petr Kala5, Martin Poloczek5, Josef Stasek6, Ludek Haman6, Marian Branny7, Jan Chovancik7, Pavel Cervinka8, Jiri Holy8, Tomas Kovarnik9, David Zemanek9, Stepan Havranek9, Vlastimil Vancura10, Petr Peichl11, Petr Tousek2, Veronika Lekesova3, Jiri Jarkovsky12, Martina Novackova12, Klara Benesova12, Petr Widimsky2, Vivek Y Reddy13. 1. Cardiocenter, Third Faculty of Medicine, Charles University Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic. Electronic address: pavel.osmancik@gmail.com. 2. Cardiocenter, Third Faculty of Medicine, Charles University Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic. 3. Cardiocenter, Department of Cardiology, Na Homolce Hospital, Prague, Czech Republic. 4. Cardiocenter, Department of Cardiology, University Hospital Olomouc, Olomouc, Czech Republic. 5. Clinic of Cardiology, Masaryk University and University Hospital Brno, Brno, Czech Republic. 6. First Department of Internal Medicine, Faculty of Medicine, University Hospital Hradec Kralove, Charles University Prague, Prague, Czech Republic. 7. Department of Cardiology, Cardiocenter, Hospital Podlesí a.s., Trinec, Czech Republic. 8. Department of Cardiology, Krajská zdravotni a.s., Masaryk Hospital and Jan Evangelista Purkyně University, Usti nad Labem, Czech Republic. 9. Cardiocenter, Second Internal Clinic-Cardiology and Angiology, Charles University, General Faculty Hospital, Prague, Czech Republic. 10. Department of Cardiology, University Hospital and Faculty of Medicine Pilsen, Pilsen, Czech Republic. 11. Cardiocenter, Institute of Clinical and Experimental Medicine, Prague, Czech Republic. 12. Institute of Biostatistics and Analysis, Faculty of Medicine, Masaryk University, Brno, Czech Republic. 13. Cardiocenter, Department of Cardiology, Na Homolce Hospital, Prague, Czech Republic; Helmsley Electrophysiology Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: vivek.reddy@mountsinai.org.
Abstract
BACKGROUND: The PRAGUE-17 (Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) was noninferior to nonwarfarin direct oral anticoagulants (DOACs) for preventing major neurological, cardiovascular, or bleeding events in patients with atrial fibrillation (AF) who were at high risk. OBJECTIVES: This study sought to assess the prespecified long-term (4-year) outcomes in PRAGUE-17. METHODS: PRAGUE-17 was a randomized noninferiority trial comparing percutaneous LAAC (Watchman or Amulet) with DOACs (95% apixaban) in patients with nonvalvular AF and with a history of cardioembolism, clinically-relevant bleeding, or both CHA2DS2-VASc ≥3 and HASBLED ≥2. The primary endpoint was a composite of cardioembolic events (stroke, transient ischemic attack, or systemic embolism), cardiovascular death, clinically relevant bleeding, or procedure-/device-related complications (LAAC group only). The primary analysis was modified intention-to-treat. RESULTS: This study randomized 402 patients with AF (201 per group, age 73.3 ± 7.0 years, 65.7% male, CHA2DS2-VASc 4.7 ±1.5, HASBLED 3.1 ± 0.9). After 3.5 years median follow-up (1,354 patient-years), LAAC was noninferior to DOACs for the primary endpoint by modified intention-to-treat (subdistribution HR [sHR]: 0.81; 95% CI: 0.56-1.18; P = 0.27; P for noninferiority = 0.006). For the components of the composite endpoint, the corresponding sHRs were 0.68 (95% CI: 0.39-1.20; P = 0.19) for cardiovascular death, 1.14 (95% CI: 0.56-2.30; P = 0.72) for all-stroke/transient ischemic attack, 0.75 (95% CI: 0.44-1.27; P = 0.28) for clinically relevant bleeding, and 0.55 (95% CI: 0.31-0.97; P = 0.039) for nonprocedural clinically relevant bleeding. The primary endpoint outcomes were similar in the per-protocol (sHR: 0.80; 95% CI: 0.54-1.18; P = 0.25) and on-treatment (sHR: 0.82; 95% CI: 0.56-1.20; P = 0.30) analyses. CONCLUSIONS: In long-term follow-up of PRAGUE-17, LAAC remains noninferior to DOACs for preventing major cardiovascular, neurological, or bleeding events. Furthermore, nonprocedural bleeding was significantly reduced with LAAC. (PRAGUE-17 [Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation]; NCT02426944).
BACKGROUND: The PRAGUE-17 (Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) was noninferior to nonwarfarin direct oral anticoagulants (DOACs) for preventing major neurological, cardiovascular, or bleeding events in patients with atrial fibrillation (AF) who were at high risk. OBJECTIVES: This study sought to assess the prespecified long-term (4-year) outcomes in PRAGUE-17. METHODS: PRAGUE-17 was a randomized noninferiority trial comparing percutaneous LAAC (Watchman or Amulet) with DOACs (95% apixaban) in patients with nonvalvular AF and with a history of cardioembolism, clinically-relevant bleeding, or both CHA2DS2-VASc ≥3 and HASBLED ≥2. The primary endpoint was a composite of cardioembolic events (stroke, transient ischemic attack, or systemic embolism), cardiovascular death, clinically relevant bleeding, or procedure-/device-related complications (LAAC group only). The primary analysis was modified intention-to-treat. RESULTS: This study randomized 402 patients with AF (201 per group, age 73.3 ± 7.0 years, 65.7% male, CHA2DS2-VASc 4.7 ±1.5, HASBLED 3.1 ± 0.9). After 3.5 years median follow-up (1,354 patient-years), LAAC was noninferior to DOACs for the primary endpoint by modified intention-to-treat (subdistribution HR [sHR]: 0.81; 95% CI: 0.56-1.18; P = 0.27; P for noninferiority = 0.006). For the components of the composite endpoint, the corresponding sHRs were 0.68 (95% CI: 0.39-1.20; P = 0.19) for cardiovascular death, 1.14 (95% CI: 0.56-2.30; P = 0.72) for all-stroke/transient ischemic attack, 0.75 (95% CI: 0.44-1.27; P = 0.28) for clinically relevant bleeding, and 0.55 (95% CI: 0.31-0.97; P = 0.039) for nonprocedural clinically relevant bleeding. The primary endpoint outcomes were similar in the per-protocol (sHR: 0.80; 95% CI: 0.54-1.18; P = 0.25) and on-treatment (sHR: 0.82; 95% CI: 0.56-1.20; P = 0.30) analyses. CONCLUSIONS: In long-term follow-up of PRAGUE-17, LAAC remains noninferior to DOACs for preventing major cardiovascular, neurological, or bleeding events. Furthermore, nonprocedural bleeding was significantly reduced with LAAC. (PRAGUE-17 [Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation]; NCT02426944).
Authors: Guy Rozen; Gilad Margolis; Ibrahim Marai; Ariel Roguin; Eldad Rahamim; David Planer; Edwin Kevin Heist; Offer Amir; Ilgar Tahiroglu; Jeremy Ruskin; Moussa Mansour; Gabby Elbaz-Greener Journal: Front Cardiovasc Med Date: 2022-09-13