Effect of digoxin vs bisoprolol for heart rate control in atrial fibrillation on patient-reported quality of life: the RATE-AF randomized clinical trial

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Effect of digoxin vs bisoprolol for heart rate control in atrial fibrillation on patient-reported quality of life : the RATE-AF randomized clinical trial. / Rate Control Therapy Evaluation in Permanent 13 Atrial Fibrillation (RATE-AF) team ; Kotecha, Dipak; Bunting, Karina; Gill, Simrat; Mehta, Samir; Stanbury, Mary; Jones, Jackie; Haynes , Sandra; Calvert, Melanie; Deeks, Jon; Steeds, Richard P; Strauss , Victoria Y ; Rahimi, Kazem; Camm, A John; Griffith, Michael; Lip, Gregory; Townend, Jonathan N; Kirchhof, Paulus.

In: JAMA The Journal of the American Medical Association, Vol. 324, No. 24, 22.12.2020, p. 2497-2508.

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Rate Control Therapy Evaluation in Permanent 13 Atrial Fibrillation (RATE-AF) team ; Kotecha, Dipak ; Bunting, Karina ; Gill, Simrat ; Mehta, Samir ; Stanbury, Mary ; Jones, Jackie ; Haynes , Sandra ; Calvert, Melanie ; Deeks, Jon ; Steeds, Richard P ; Strauss , Victoria Y ; Rahimi, Kazem ; Camm, A John ; Griffith, Michael ; Lip, Gregory ; Townend, Jonathan N ; Kirchhof, Paulus. / Effect of digoxin vs bisoprolol for heart rate control in atrial fibrillation on patient-reported quality of life : the RATE-AF randomized clinical trial. In: JAMA The Journal of the American Medical Association. 2020 ; Vol. 324, No. 24. pp. 2497-2508.

Bibtex

@article{ecd5f704dadf435e86089183a3764d36,
title = "Effect of digoxin vs bisoprolol for heart rate control in atrial fibrillation on patient-reported quality of life: the RATE-AF randomized clinical trial",
abstract = "Importance: There is little evidence to support selection of rate-control therapy in the growing population with permanent atrial fibrillation (AF), in particular those with coexisting heart failure.Objective: To compare low-dose digoxin with beta-blockers. Design, Setting, and Participants: Randomized, open-label, blinded end-point trial of 160 patients aged ≥60 years with permanent AF, defined as no plans to restore sinus rhythm, and at least NYHA class II dyspnea; recruitment from 3 hospitals and primary care in England 2016-2018, with last follow-up October 2019. Interventions: 1:1 randomization to digoxin (n=80; 62.5-250mcg daily; mean 161mcg) or bisoprolol (n=80; 1.25-15mg daily; mean 3.2mg).Main Outcomes and Measures: The primary endpoint was patient-reported quality of life using the SF36 Physical Component Summary (PCS) at 6-months (higher better; range 0-100), with a minimal clinically-important difference of 0.5 SD. There were 17 and 20 secondary endpoints at 6 and 12-months respectively, including other QoL outcomes, heart rate, modified European Heart Rhythm Association (mEHRA) symptom classification and NTpro-B-type natriuretic peptide (BNP); in addition to adverse event reporting.Results: Among 160 patients (mean age, 75.6 years; 74 (46%) women; mean baseline heart rate, 100 [18] beats/min), 145 (91%) completed the trial and 150 (94%) completed were included in the analysis for the primary endpointoutcome. Baseline heart rate was 100±18 beats/min, with no significant difference between groups at any time-point. There was no significant difference in the primary outcome: normalized SF36-PCS at 6-months 31.9±11.7 for digoxin and 29.7±11.4 for beta-blockers; adjusted mean difference 1.4, -1.1 to 3.8; p=0.28. Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (76.9 [12.1] with digoxin vs 74.8 [11.6] with bisoprolol; difference 1.5 beats/min, 95% CI -2.0 to 5.1; p=0.40). Of the 17 secondary comparisons at 6-months, only mEHRA class was significantly different between groups, with 53% reporting a two-class improvement with digoxin, versus 9% for beta-blockers (adjusted OR 10.3, 4.0-26.6; p<0.001). By 12-months, 8 of 20 outcomes were significantly different (all favoring digoxin), with median NTproBNP 960 pg/mL (626-1531) with digoxin and 1250 pg/mL (847-1890) with beta-blockers; ratio 0.77, 0.64-0.92; p=0.005. Twelve outcomes were not significantly different between groups, including resting heart rate (75.4 [9.9] with digoxin vs 74.3 [11.2] with bisoprolol; difference, 0.3 beats/min, 95% CI -3.0 to 3.5; p=0.87).By 12-months, 8/20 outcomes were significantly different (all favoring digoxin) and 12 null. Median NTproBNP was 960 pg/mL in the digoxin group (626-1531) and 1250 pg/mL for beta-blockers (847-1890); ratio 0.77, 0.64-0.92; p=0.005. Adverse events were less common with digoxin, with 20 patients (25%) having at least one event versus 51 (64%) for beta-blockers (p<0.001). The total number of adverse and serious adverse events was 29 and 16 for digoxin, versus 142 and 37 for beta-blockers. Conclusion and relevance: Among patients aged 60 and older with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support basing decisions about treatment on other endpoints. Trial registration: clinicaltrials.gov NCT02391337; ISRCTN 95259705; EudraCT 2015-005043-13.",
author = "{Rate Control Therapy Evaluation in Permanent 13 Atrial Fibrillation (RATE-AF) team} and Dipak Kotecha and Karina Bunting and Simrat Gill and Samir Mehta and Mary Stanbury and Jackie Jones and Sandra Haynes and Melanie Calvert and Jon Deeks and Steeds, {Richard P} and Strauss, {Victoria Y} and Kazem Rahimi and Camm, {A John} and Michael Griffith and Gregory Lip and Townend, {Jonathan N} and Paulus Kirchhof",
year = "2020",
month = dec,
day = "22",
doi = "10.1001/jama.2020.23138",
language = "English",
volume = "324",
pages = "2497--2508",
journal = "JAMA The Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Association",
number = "24",

}

RIS

TY - JOUR

T1 - Effect of digoxin vs bisoprolol for heart rate control in atrial fibrillation on patient-reported quality of life

T2 - the RATE-AF randomized clinical trial

AU - Rate Control Therapy Evaluation in Permanent 13 Atrial Fibrillation (RATE-AF) team

AU - Kotecha, Dipak

AU - Bunting, Karina

AU - Gill, Simrat

AU - Mehta, Samir

AU - Stanbury, Mary

AU - Jones, Jackie

AU - Haynes , Sandra

AU - Calvert, Melanie

AU - Deeks, Jon

AU - Steeds, Richard P

AU - Strauss , Victoria Y

AU - Rahimi, Kazem

AU - Camm, A John

AU - Griffith, Michael

AU - Lip, Gregory

AU - Townend, Jonathan N

AU - Kirchhof, Paulus

PY - 2020/12/22

Y1 - 2020/12/22

N2 - Importance: There is little evidence to support selection of rate-control therapy in the growing population with permanent atrial fibrillation (AF), in particular those with coexisting heart failure.Objective: To compare low-dose digoxin with beta-blockers. Design, Setting, and Participants: Randomized, open-label, blinded end-point trial of 160 patients aged ≥60 years with permanent AF, defined as no plans to restore sinus rhythm, and at least NYHA class II dyspnea; recruitment from 3 hospitals and primary care in England 2016-2018, with last follow-up October 2019. Interventions: 1:1 randomization to digoxin (n=80; 62.5-250mcg daily; mean 161mcg) or bisoprolol (n=80; 1.25-15mg daily; mean 3.2mg).Main Outcomes and Measures: The primary endpoint was patient-reported quality of life using the SF36 Physical Component Summary (PCS) at 6-months (higher better; range 0-100), with a minimal clinically-important difference of 0.5 SD. There were 17 and 20 secondary endpoints at 6 and 12-months respectively, including other QoL outcomes, heart rate, modified European Heart Rhythm Association (mEHRA) symptom classification and NTpro-B-type natriuretic peptide (BNP); in addition to adverse event reporting.Results: Among 160 patients (mean age, 75.6 years; 74 (46%) women; mean baseline heart rate, 100 [18] beats/min), 145 (91%) completed the trial and 150 (94%) completed were included in the analysis for the primary endpointoutcome. Baseline heart rate was 100±18 beats/min, with no significant difference between groups at any time-point. There was no significant difference in the primary outcome: normalized SF36-PCS at 6-months 31.9±11.7 for digoxin and 29.7±11.4 for beta-blockers; adjusted mean difference 1.4, -1.1 to 3.8; p=0.28. Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (76.9 [12.1] with digoxin vs 74.8 [11.6] with bisoprolol; difference 1.5 beats/min, 95% CI -2.0 to 5.1; p=0.40). Of the 17 secondary comparisons at 6-months, only mEHRA class was significantly different between groups, with 53% reporting a two-class improvement with digoxin, versus 9% for beta-blockers (adjusted OR 10.3, 4.0-26.6; p<0.001). By 12-months, 8 of 20 outcomes were significantly different (all favoring digoxin), with median NTproBNP 960 pg/mL (626-1531) with digoxin and 1250 pg/mL (847-1890) with beta-blockers; ratio 0.77, 0.64-0.92; p=0.005. Twelve outcomes were not significantly different between groups, including resting heart rate (75.4 [9.9] with digoxin vs 74.3 [11.2] with bisoprolol; difference, 0.3 beats/min, 95% CI -3.0 to 3.5; p=0.87).By 12-months, 8/20 outcomes were significantly different (all favoring digoxin) and 12 null. Median NTproBNP was 960 pg/mL in the digoxin group (626-1531) and 1250 pg/mL for beta-blockers (847-1890); ratio 0.77, 0.64-0.92; p=0.005. Adverse events were less common with digoxin, with 20 patients (25%) having at least one event versus 51 (64%) for beta-blockers (p<0.001). The total number of adverse and serious adverse events was 29 and 16 for digoxin, versus 142 and 37 for beta-blockers. Conclusion and relevance: Among patients aged 60 and older with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support basing decisions about treatment on other endpoints. Trial registration: clinicaltrials.gov NCT02391337; ISRCTN 95259705; EudraCT 2015-005043-13.

AB - Importance: There is little evidence to support selection of rate-control therapy in the growing population with permanent atrial fibrillation (AF), in particular those with coexisting heart failure.Objective: To compare low-dose digoxin with beta-blockers. Design, Setting, and Participants: Randomized, open-label, blinded end-point trial of 160 patients aged ≥60 years with permanent AF, defined as no plans to restore sinus rhythm, and at least NYHA class II dyspnea; recruitment from 3 hospitals and primary care in England 2016-2018, with last follow-up October 2019. Interventions: 1:1 randomization to digoxin (n=80; 62.5-250mcg daily; mean 161mcg) or bisoprolol (n=80; 1.25-15mg daily; mean 3.2mg).Main Outcomes and Measures: The primary endpoint was patient-reported quality of life using the SF36 Physical Component Summary (PCS) at 6-months (higher better; range 0-100), with a minimal clinically-important difference of 0.5 SD. There were 17 and 20 secondary endpoints at 6 and 12-months respectively, including other QoL outcomes, heart rate, modified European Heart Rhythm Association (mEHRA) symptom classification and NTpro-B-type natriuretic peptide (BNP); in addition to adverse event reporting.Results: Among 160 patients (mean age, 75.6 years; 74 (46%) women; mean baseline heart rate, 100 [18] beats/min), 145 (91%) completed the trial and 150 (94%) completed were included in the analysis for the primary endpointoutcome. Baseline heart rate was 100±18 beats/min, with no significant difference between groups at any time-point. There was no significant difference in the primary outcome: normalized SF36-PCS at 6-months 31.9±11.7 for digoxin and 29.7±11.4 for beta-blockers; adjusted mean difference 1.4, -1.1 to 3.8; p=0.28. Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (76.9 [12.1] with digoxin vs 74.8 [11.6] with bisoprolol; difference 1.5 beats/min, 95% CI -2.0 to 5.1; p=0.40). Of the 17 secondary comparisons at 6-months, only mEHRA class was significantly different between groups, with 53% reporting a two-class improvement with digoxin, versus 9% for beta-blockers (adjusted OR 10.3, 4.0-26.6; p<0.001). By 12-months, 8 of 20 outcomes were significantly different (all favoring digoxin), with median NTproBNP 960 pg/mL (626-1531) with digoxin and 1250 pg/mL (847-1890) with beta-blockers; ratio 0.77, 0.64-0.92; p=0.005. Twelve outcomes were not significantly different between groups, including resting heart rate (75.4 [9.9] with digoxin vs 74.3 [11.2] with bisoprolol; difference, 0.3 beats/min, 95% CI -3.0 to 3.5; p=0.87).By 12-months, 8/20 outcomes were significantly different (all favoring digoxin) and 12 null. Median NTproBNP was 960 pg/mL in the digoxin group (626-1531) and 1250 pg/mL for beta-blockers (847-1890); ratio 0.77, 0.64-0.92; p=0.005. Adverse events were less common with digoxin, with 20 patients (25%) having at least one event versus 51 (64%) for beta-blockers (p<0.001). The total number of adverse and serious adverse events was 29 and 16 for digoxin, versus 142 and 37 for beta-blockers. Conclusion and relevance: Among patients aged 60 and older with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support basing decisions about treatment on other endpoints. Trial registration: clinicaltrials.gov NCT02391337; ISRCTN 95259705; EudraCT 2015-005043-13.

U2 - 10.1001/jama.2020.23138

DO - 10.1001/jama.2020.23138

M3 - Article

VL - 324

SP - 2497

EP - 2508

JO - JAMA The Journal of the American Medical Association

JF - JAMA The Journal of the American Medical Association

SN - 0098-7484

IS - 24

ER -