Atrial overdrive pacing to prevent atrial fibrillation: Insights from ASSERT Stefan H. Hohnloser, MD, FACC, FESC, FHRS,* Jeff S. Healey, MD, FHRS, † Michael R. Gold, MD, FHRS, ‡ Carsten W. Israel, MD,* Sean Yang, PhD, † Isabelle van Gelder, MD, § Alessandro Capucci, MD,  Chu P. Lau, MD, ¶ Eric Fain, MD, # Carlos A. Morillo, MD,* Andrew Ha, MD, † Mark Carlson, MD, # Stuart J. Connolly, MD, † on behalf of the ASSERT Investigators From the *J.W. Goethe University, Frankfurt, Germany, † Population Health Research Institute, McMaster University, Hamilton, Canada, ‡ Medical University of South Carolina, Charleston, South Carolina, § Thoraxcenter, Groningen, The Netherlands,  Clinica di Cardiologia, Università Politecnica delle Marche, Ancona, Italy, ¶ St Mary’s Hospital, Hong Kong, China, and # St Jude Medical, Sylmar, California. BACKGROUND Pacing algorithms to prevent atrial fibrillation (AF) have been tested in studies of modest size and duration with inconclusive results. OBJECTIVES To prospectively evaluate the relationship between subclinical AF and stroke in patients 65 years of age or older with no previous AF receiving a first pacemaker or an implantable cardioverter-defibrillator for standard indications. Three months following device implantation, pacemaker patients were random- ized to have continuous atrial overdrive pacing (CAOP) algorithm turned “ON” or “OFF.” The primary study outcome was develop- ment of electrocardiogram-documented AF 6 minutes. RESULTS A total of 2343 patients were randomized and followed for a mean of 2.5 years. The primary outcome occurred in 60 patients in the CAOP ON group (1.96% per year) and in 45 in the CAOP OFF group (1.44% per year; relative risk 1.38; 95% confi- dence interval 0.94 –2.03; P = .10). Major clinical events (stroke, myocardial infarct, cardiovascular death, systemic embolism, heart failure hospitalization) occurred at similar frequencies in the 2 groups. In the CAOP ON group, 133 of the 1164 patients (11.4%) crossed over to CAOP OFF compared with 12 of the 1179 (1.0%) who crossed over from OFF to ON (P .0001). False-positive device detections of AF were more common among patients assigned to CAOP ON (23%) than among patients assigned to CAOP OFF (7.7%; relative risk 2.99; 95% confidence interval 2.40 –3.74; P .001). Pacemaker generator replacement for battery depletion occurred in 4.4% of the subjects randomized to CAOP ON and in 2.5% of the patients assigned to CAOP OFF (relative risk 1.70; 95% confidence interval 1.08 –2.67; P = .02). CONCLUSIONS CAOP does not prevent new-onset AF, is poorly tolerated, and accelerates pulse generator battery depletion. KEYWORDS Atrial fibrillation; Pacemaker; Preventive pacing ABBREVIATIONS AF = atrial fibrillation; ASSERT = ASymptom- atic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial; AT = atrial tachycardia; CAOP = continuous atrial overdrive pacing; CI = con- fidence interval; RNVAS = repetitive non-reentrant ventriculoatrial synchrony (Heart Rhythm 2012;9:1667–1673) © 2012 Heart Rhythm Society. All rights reserved. This study was sponsored by St Jude Medical, Sylmar, CA (NCT00256152). Dr Hohnloser reports receiving consulting fees from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, and Cardiome and lecture fees from Sanofi-Aventis, St Jude Medical, Boehr- inger Ingelheim, Bristol-Myers Squibb, and Pfizer; Dr Healey reports receiving consulting fees from St Jude Medical, Boehringer Ingelheim, and Bayer and grant support from Boehringer Ingelheim, Boston Scientific, and AstraZeneca; Dr Gold reports receiving fees for board membership from St Jude Medical and Medtronic; consulting fees from St Jude Medical and Medtronic; grant support from St Jude Medical, Boston Scientific, Sorin, and Medtronic; and lecture fees from St Jude Medical, Boston Scientific, Sorin, Medtronic, and Biotronik; Dr Israel reports receiving fees for board membership from Medtronic and lecture fees and reimbursement for travel expenses from Boston Scientific, Medtronic, Sorin, St Jude Medical, and Biotronik; Dr Van Gelder reports receiving consulting fees from Boehringer Ingelheim, Medtronic, and Sanofi-Aventis; grant support from Medtronic and Biotronik; and lecture fees from Boehringer Ingelheim, Medtronic, Merck, and Sanofi-Aventis; Dr Capucci reports receiving consulting fees from Merck, Sanofi-Aventis, and Meda Pharmaceuticals; lecture fees from Merck and Sanofi-Aventis; and reimbursement for meeting expenses from Sorin, Boston Scientific, Merck, and Sanofi-Aventis; Dr Fain reports being employed by and receiving stock, fees for patents, and reimbursement for meeting expenses from St Jude Medical; Dr Morillo reports receiving consulting fees from St Jude Medical, Biotronik, Medtronic, Boston Scientific, Sanofi-Aventis, and Boehringer Ingelheim; grant support from St Jude Medical, Medtronic, and Boston Scientific; and lecture fees from Boston Scientific, St Jude Medical, Medtronic, Boehringer Ingelheim, Sanofi-Aventis, and Biotronik; Dr Carlson reports being employed by and receiving grant support, stock, and reimburse- ment for meeting expenses from St Jude Medical; Dr Connolly reports receiv- ing grant support and lecture fees from St Jude Medical. Address for reprint requests and correspondence: Dr Stefan H. Hohnloser, MD, FACC, FESC, FHRS, Division of Clinical Electrophysiology, J.W. Goethe University Hospital, Theodor-Stern-Kai 7, D 60590 Frankfurt, Ger- many. E-mail address: Hohnloser@em.uni-frankfurt.de. 1547-5271/$ -see front matter © 2012 Heart Rhythm Society. All rights reserved. http://dx.doi.org/10.1016/j.hrthm.2012.06.012