PMID- 35243434
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220502
IS  - 2666-5018 (Electronic)
IS  - 2666-5018 (Linking)
VI  - 3
IP  - 1
DP  - 2022 Feb
TI  - Dose-limiting, adverse event-associated bradycardia with beta-blocker treatment of 
      atrial fibrillation in the GENETIC-AF trial.
PG  - 40-49
LID - 10.1016/j.hroo.2021.11.005 [doi]
AB  - BACKGROUND: Heart failure (HF) patients with atrial fibrillation (AF) often have 
      conduction system disorders, which may be worsened by beta-blocker therapy. 
      OBJECTIVE: In a post hoc analysis we examined the prevalence of bradycardia and 
      its association with adverse events (AEs) and failure to achieve target dose in 
      the GENETIC-AF trial. METHODS: Patients randomized to metoprolol (n = 125) or 
      bucindolol (n = 131) entering 24-week efficacy follow-up and receiving study 
      medication were evaluated. Bradycardia was defined as an electrocardiogram (ECG) 
      heart rate (HR) <60 beats per minute (bpm) and severe bradycardia <50 bpm. 
      RESULTS: Mean HR in sinus rhythm (SR) was 62.6 +/- 12.5 bpm for metoprolol and 68.3 
      +/- 11.1 bpm for bucindolol (P < .0001), but in AF HRs were not different (87.5 bpm 
      vs 89.7 bpm, respectively). Episodes per patient for bucindolol vs metoprolol 
      were 0.82 vs 2.08 (P < .001) for bradycardia and 0.24 vs 0.57 for severe 
      bradycardia (P < .001), with 98.9% of the episodes occurring in SR. Patients 
      experiencing bradycardia had a 4.15-fold higher prevalence of study medication 
      dose reduction (P <.0001) compared to patients without bradycardia. Fewer 
      patients receiving metoprolol were at target dose (61.7% vs 74.9% for bucindolol, 
      P < .0001) at ECG recordings, and bradycardia AEs were more prevalent in the 
      metoprolol group (13 vs 1 for bucindolol, P = .001). On multivariate analysis of 
      21 candidate bradycardia predictors including presence of a device with pacing 
      capability, bucindolol treatment was associated with the greatest degree of 
      prevention (Z(odds ratio) -4.24, P < .0001). CONCLUSION: In AF-prone HF patients 
      bradycardia may limit the effectiveness of beta blockers, and this property is 
      agent-dependent.
CI  - (c) 2021 Heart Rhythm Society. Published by Elsevier Inc.
FAU - Abraham, William T
AU  - Abraham WT
AD  - Ohio State University Medical Center, Columbus, Ohio.
FAU - Piccini, Jonathan P
AU  - Piccini JP
AD  - Duke Clinical Research Institute and Duke University Medical Center, Durham, 
      North Carolina.
FAU - Dufton, Christopher
AU  - Dufton C
AD  - ARCA biopharma, Inc, Westminster, Colorado.
FAU - Carroll, Ian A
AU  - Carroll IA
AD  - ARCA biopharma, Inc, Westminster, Colorado.
FAU - Healey, Jeffrey S
AU  - Healey JS
AD  - Population Health Research Institute, McMaster University, Hamilton, California.
FAU - O'Connor, Christopher M
AU  - O'Connor CM
AD  - Inova Heart and Vascular Institute, Fairfax, Virginia.
FAU - Marshall, Debra
AU  - Marshall D
AD  - ARCA biopharma, Inc, Westminster, Colorado.
FAU - Aleong, Ryan
AU  - Aleong R
AD  - University of Colorado Anschutz Medical Campus Division of Cardiology, Aurora, 
      Colorado.
FAU - van Veldhuisen, Dirk J
AU  - van Veldhuisen DJ
AD  - University of Groningen, University Medical Center, Groningen, the Netherlands.
FAU - Rienstra, Michiel
AU  - Rienstra M
AD  - University of Groningen, University Medical Center, Groningen, the Netherlands.
FAU - Wilton, Stephen B
AU  - Wilton SB
AD  - Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, 
      Canada.
FAU - White, Michel
AU  - White M
AD  - Montreal Heart Institute, Montreal, Canada.
FAU - Sauer, William H
AU  - Sauer WH
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
FAU - Anand, Inder S
AU  - Anand IS
AD  - University of Minnesota, Minneapolis, Minnesota.
FAU - Huebler, Sophia P
AU  - Huebler SP
AD  - ARCA biopharma, Inc, Westminster, Colorado.
FAU - Connolly, Stuart J
AU  - Connolly SJ
AD  - Population Health Research Institute, McMaster University, Hamilton, California.
FAU - Bristow, Michael R
AU  - Bristow MR
AD  - ARCA biopharma, Inc, Westminster, Colorado.
AD  - University of Colorado Anschutz Medical Campus Division of Cardiology, Aurora, 
      Colorado.
LA  - eng
PT  - Journal Article
DEP - 20211114
PL  - United States
TA  - Heart Rhythm O2
JT  - Heart rhythm O2
JID - 101768511
PMC - PMC8859785
OTO - NOTNLM
OT  - Atrial fibrillation
OT  - Beta blockers
OT  - Bradyarrhythmias
OT  - Heart failure
OT  - Pharmacogenetics
EDAT- 2022/03/05 06:00
MHDA- 2022/03/05 06:01
PMCR- 2021/11/14
CRDT- 2022/03/04 05:44
PHST- 2022/03/04 05:44 [entrez]
PHST- 2022/03/05 06:00 [pubmed]
PHST- 2022/03/05 06:01 [medline]
PHST- 2021/11/14 00:00 [pmc-release]
AID - S2666-5018(21)00215-4 [pii]
AID - 10.1016/j.hroo.2021.11.005 [doi]
PST - epublish
SO  - Heart Rhythm O2. 2021 Nov 14;3(1):40-49. doi: 10.1016/j.hroo.2021.11.005. 
      eCollection 2022 Feb.