Author + information
- Received January 30, 2020
- Revision received April 20, 2020
- Accepted April 20, 2020
- Published online June 22, 2020.
- Pavel Osmancik, MD, PhDa,∗ (, )@POsmancik,
- Dalibor Herman, MD, PhDa,
- Petr Neuzil, MD, CScb,
- Pavel Hala, MDb,
- Milos Taborsky, MD, CScc,
- Petr Kala, MD, PhDd,
- Martin Poloczek, MDd,
- Josef Stasek, MD, PhDe,
- Ludek Haman, MD, PhDe,
- Marian Branny, MD, PhDf,
- Jan Chovancik, MDf,
- Pavel Cervinka, MD, PhDg,
- Jiri Holy, MDg,
- Tomas Kovarnik, MD, PhDh,
- David Zemanek, MD, PhDh,
- Stepan Havranek, MD, PhDh,
- Vlastimil Vancura, MD, PhDi,
- Jan Opatrny, MDi,
- Petr Peichl, MD, PhDj,
- Petr Tousek, MD, PhDa,
- Veronika Lekesova, MDb,
- Jiri Jarkovsky, RNDr, PhDk,
- Martina Novackova, Mgrk,
- Klara Benesova, Mgrk,
- Petr Widimsky, MD, DrSca,∗,
- Vivek Y. Reddy, MDb,l,∗∗∗ (, )
- on behalf of the PRAGUE-17 Trial Investigators
- aCardiocenter, Third Faculty of Medicine, Charles University Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic
- bCardiocenter, Department of Cardiology, Na Homolce Hospital, Prague, Czech Republic
- cCardiocenter, Department of Cardiology, University Hospital Olomouc, Olomouc, Czech Republic
- dClinic of Cardiology, Masaryk University and University Hospital Brno, Brno, Czech Republic
- eFirst Department of Internal Medicine, Faculty of Medicine, University Hospital Hradec Kralove, Charles University Prague, Prague, Czech Republic
- fDepartment of Cardiology, Cardiocenter, Hospital Podlesí a.s., Trinec, Czech Republic
- gDepartment of Cardiology, Krajská zdravotni a.s., Masaryk Hospital and J.E.Purkyne University, Usti nad Labem, Czech Republic
- hCardiocenter, Second Internal Clinic—Cardiology and Angiology, Charles University, General Faculty Hospital, Prague, Czech Republic
- iDepartment of Cardiology, University Hospital and Faculty of Medicine Pilsen, Pilsen, Czech Republic
- jCardiocenter, Institute of Clinical and Experimental Medicine, Prague, Czech Republic
- kMasaryk University, Institute of Biostatistics and Analyses, Brno, Czech Republic
- lHelmsley Electrophysiology Center, Icahn School of Medicine at Mount Sinai, New York, New York
- ↵∗Address for correspondence:
Dr. Pavel Osmancik, Cardiocenter, Charles University Prague, Third Internal–Cardiology Clinic, Srobarova 50, 10034 Prague, Czech Republic.
- ↵∗∗Dr. Vivek Y. Reddy, Helmsley Electrophysiology Center, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, New York 10029.
Background Percutaneous left atrial appendage closure (LAAC) is noninferior to vitamin K antagonists (VKAs) for preventing atrial fibrillation (AF)–related stroke. However, direct oral anticoagulants (DOACs) have an improved safety profile over VKAs, and their effect on cardiovascular and neurological outcomes relative to LAAC is unknown.
Objectives This study sought to compare DOACs with LAAC in high-risk patients with AF.
Methods Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation (PRAGUE-17) was a multicenter, randomized, noninferiority trial comparing LAAC with DOACs. Patients were eligible to be enrolled if they had nonvalvular AF; were indicated for oral anticoagulation (OAC); and had a history of bleeding requiring intervention or hospitalization, a history of a cardioembolic event while taking an OAC, and/or a CHA2DS2-VASc of ≥3 and HAS-BLED of >2. Patients were randomized to receive LAAC or DOAC. The primary composite outcome was stroke, transient ischemic attack, systemic embolism, cardiovascular death, major or nonmajor clinically relevant bleeding, or procedure-/device-related complications. The primary analysis was by modified intention to treat.
Results A high-risk patient cohort (CHA2DS2-VASc: 4.7 ± 1.5) was randomized to receive LAAC (n = 201) or DOAC (n = 201). LAAC was successful in 181 of 201 (90.0%) patients. In the DOAC group, apixaban was most frequently used (192 of 201; 95.5%). At a median 19.9 months of follow-up, the annual rates of the primary outcome were 10.99% with LAAC and 13.42% with DOAC (subdistribution hazard ratio [sHR]: 0.84; 95% confidence interval [CI]: 0.53 to 1.31; p = 0.44; p = 0.004 for noninferiority). There were no differences between groups for the components of the composite endpoint: all-stroke/TIA (sHR: 1.00; 95% CI: 0.40 to 2.51), clinically significant bleeding (sHR: 0.81; 95% CI: 0.44 to 1.52), and cardiovascular death (sHR: 0.75; 95% CI: 0.34 to 1.62). Major LAAC-related complications occurred in 9 (4.5%) patients.
Conclusions Among patients at high risk for stroke and increased risk of bleeding, LAAC was noninferior to DOAC in preventing major AF-related cardiovascular, neurological, and bleeding events. (Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation [PRAGUE-17]; NCT02426944)
↵∗ Drs. Widimsky and Reddy are co-senior authors.
This work was supported by a research grant from the Ministry of Health, Czech Republic (AZV 15-29565A). Dr. Osmancik has received occasional speaking honoraria from Bayer and Abbott. Dr. Taborsky has served on the Advisory Boards for Bayer and Pfizer. Dr. Kala has served on the Speakers Bureau and Advisory Board for Bayer; and has served on the Advisory Board and as a consultant for Boston Scientific. Dr. Poloczek has received speaking honoraria from Abbott. Dr. Haman has received speaking honoraria from Pfizer. Dr. Zemanek has received speaking honoraria from Abbott and Bayer. Dr. Widimsky has received honoraria from Bayer, Pfizer, and Boehringer Ingelheim. Dr. Reddy has received consulting income and grant support from Abbott Inc. and Boston Scientific Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Jacqueline Saw, MD, served as Guest Associate Editor for this paper. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received January 30, 2020.
- Revision received April 20, 2020.
- Accepted April 20, 2020.
- 2020 American College of Cardiology Foundation
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