Dose-limiting, adverse event-associated bradycardia with β-blocker treatment of atrial fibrillation in the GENETIC-AF trial

被引：3

作者：

Abraham, William T. ^{[1
]}

Piccini, Jonathan P. ^{[2
,3
]}

Dufton, Christopher ^{[4
]}

Carroll, Ian A. ^{[4
]}

Healey, Jeffrey S. ^{[5
]}

O'Connor, Christopher M. ^{[6
]}

Marshall, Debra ^{[4
]}

Aleong, Ryan ^{[7
]}

Van Veldhuisen, Dirk J. ^{[8
]}

Rienstra, Michiel ^{[8
]}

Wilton, Stephen B. ^{[9
]}

White, Michel ^{[10
]}

Sauer, William H. ^{[11
,12
]}

Anand, Inder S. ^{[13
]}

Huebler, Sophia P. ^{[4
]}

Connolly, Stuart J. ^{[5
]}

Bristow, Michael R. ^{[4
,7
]}

机构：

[1] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA

[2] Duke Clin Res Inst, Durham, NC USA

[3] Duke Univ, Med Ctr, Durham, NC USA

[4] ARCA Biopharma Inc, Westminster, CO USA

[5] McMaster Univ, Populat Hlth Res Inst, Hamilton, CA USA

[6] Inova Heart & Vasc Inst, Fairfax, VA USA

[7] Univ Colorado, Div Cardiol, Anschutz Med Campus, Aurora, CO USA

[8] Univ Groningen, Univ Med Ctr, Groningen, Netherlands

[9] Univ Calgary, Libin Cardiovasc Inst Alberta, Calgary, AB, Canada

[10] Montreal Heart Inst, Montreal, PQ, Canada

[11] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[12] Harvard Med Sch, Boston, MA 02115 USA

[13] Univ Minnesota, Minneapolis, MN USA

来源：

HEART RHYTHM O2 | 2022年 / 3卷 / 01期

关键词：

Atrial fibrillation; Heart failure; Bradyarrhythmias; Beta blockers; Pharmacogenetics; CHRONIC HEART-FAILURE; BUCINDOLOL; POLYMORPHISM; DYSFUNCTION;

D O I：

10.1016/j.hroo.2021.11.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Heart failure (HF) patients with atrial fibrillation (AF) often have conduction system disorders, which may be worsened by b-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 5 125) or bucindolol (n 5 131) 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, P5.001). 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.

引用

页码：40 / 49

页数：10

共 22 条

[1] Prevention of Atrial Fibrillation by Bucindolol Is Dependent on the Beta1389 Arg/Gly Adrenergic Receptor Polymorphism [J].