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CLINICAL OUTCOMES OF ATRIAL FIBRILLATION PATIENTS RECEIVING DIGOXIN IN THE RE-LY® TRIAL
802 JACC April 5, 2016 Volume 67, Issue 13
Arrhythmias and Clinical EP CLINICAL OUTCOMES OF ATRIAL FIBRILLATION PATIENTS RECEIVING DIGOXIN IN THE RE-LY® TRIAL Poster Contributions Poster Area, South Hall A1 Sunday, April 03, 2016, 9:45 a.m.-10:30 a.m. Session Title: Can Trials Help Us Better Treat Atrial Fibrillation? Abstract Category: 16. Arrhythmias and Clinical EP: AF/SVT Presentation Number: 1188-351 Authors: Rangadham Nagarakanti, Stuart Connolly, Mandy Fraessdorf, Martina Brueckmann, Joerg Kreuzer, Paul Reilly, Jonas Oldgren, Salim Yusuf, Lars Wallentin, Michael Ezekowitz, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Background: Safety and efficacy of dabigatran etexilate (DE) vs warfarin was compared in RE-LY patients with or without digoxin at baseline and during follow up.
Methods: Baseline characteristics were compared by Fisher’s exact- or t-test. Event rates were reported for subgroups and treatment. Cox regression hazards models provided hazard ratios.
Results: Of 18,113 patients, 29% on DE or warfarin received digoxin at baseline. Of 6173 patients who received digoxin at least once, 5329 received it >50 to ≤100% of the time and 844 received it ≤50% of the time. Patients on digoxin (vs none) were younger, more often had heart failure (HF), valvular heart disease and diabetes, but less often coronary artery disease (all p < 0.0001). CHADS2 scores were slightly higher in digoxin users (2.2 vs 2.1; p < 0.0001). In patients with digoxin >50 to ≤100% of time vs no digoxin, there was higher rate of stroke and systemic embolism (SSE) (p <0.0001), ischemic stroke (p = 0.0002) and risk of death (p < 0.0001) (Table), even after multivariate adjustment for covariates. Rates of hospitalization, intracranial and major bleeds were similar with digoxin vs none. Irrespective of digoxin use, benefits of DE vs warfarin were similar in terms of SSE, major, life-threatening or intracranial bleeds (Table). Conclusions: Digoxin use was associated with higher risk of death and stroke vs non-use. Irrespective of digoxin use, patients derived similar relative benefits of DE indicating no adverse drug interaction on clinical outcomes. Table: Treatment effects of dabigatran vs. warfarin Digoxin use
Annual rate Dabigatran 110 mg bid
Annual rate Dabigatran 150 mg bid
Annual rate Warfarin
Digoxin at baseline; No Digoxin at baseline
2.04 1.33
1.32 1.04
2.10 1.57
Stroke + Systemic embolism Digoxin during treatment
Never used Digoxin Digoxin during study (0 to ≤50%); Digoxin during study (50 to ≤100%); Digoxin always (100%)
1.28 1.39 2.12 1.85
0.91 1.66 1.51 1.22
1.46 3.44 2.04 2.02
Haemorrhagic stroke
Digoxin at baseline No Digoxin at baseline
0.17 0.10
0.17 0.07
0.47 0.35
Death
Digoxin at baseline No Digoxin at baseline
4.85 3.29
4.54 3.27
5.86 3.42
MI (including silent)
Digoxin at baseline No Digoxin at baseline
0.94 0.78
1.06 0.70
0.67 0.62
Major bleed
Digoxin at baseline No Digoxin at baseline
3.12 2.83
3.38 3.45
4.29 3.33
Life-threatening bleed
Digoxin at baseline No Digoxin at baseline
1.59 1.13
1.52 1.52
2.13 1.77
Intracranial haemorrhage
Digoxin at baseline No Digoxin at baseline
0.28 0.20
0.43 0.28
0.88 0.73
Any bleeding
Digoxin at baseline No Digoxin at baseline
14.05 15.09
15.55 17.02
17.74 18.66
Outcome (ITT) Stroke + Systemic embolism Digoxin at baseline
DE 110 mg vs. warfarin HR (95% CI)
DE 150 mg vs. warfarin HR (95% CI)
0.97 (0.70, 1.35) 0.85 (0.66, 1.09) p-inter = 0.5234 0.88 (0.67, 1.15) 0.40 (0.17, 0.91) 1.05 (0.76, 1.45) 0.92 (0.63, 1.32) p-inter (0 - ≤50% vs. never) = 0.0733 p-inter (50 to ≤100% vs. never) = 0.4340 p-inter (always vs. never) = 0.8757 0.37 (0.14, 0.94) 0.27 (0.13, 0.60) p-inter = 0.6634 0.82 (0.67, 1.01) 0.96 (0.81, 1.13) p-inter = 0.2510 1.40 (0.82, 2.39) 1.25 (0.87, 1.80) p-inter = 0.7414 0.72 (0.56, 0.93) 0.85 (0.71, 1.01) p-inter = 0.2949 0.75 (0.53, 1.06) 0.64 (0.49, 0.83) p-inter = 0.4971 0.33 (0.16, 0.67) 0.28 (0.16, 0.47) p-inter = 0.7480 0.78 (0.69, 0.88) 0.78 (0.73, 0.84) p-inter = 0.9767
0.63 (0.43, 0.91) 0.66 (0.51, 0.87) p-inter = 0.8138 0.62 (0.46, 0.83) 0.48 (0.22, 1.03) 0.74 (0.52, 1.06) 0.60 (0.39, 0.91) p-inter (0 - ≤50% vs. never) = 0.5364 p-inter (50 to ≤100% vs. never) = 0.4492 p-inter (always vs. never) = 0.8961 0.37 (0.15, 0.95) 0.20 (0.08, 0.49) p-inter = 0.3582 0.77 (0.63, 0.95) 0.96 (0.81, 1.13) p-inter = 0.1076 1.60 (0.95, 2.69) 1.13 (0.78, 1.63) p-inter = 0.2930 0.76 (0.60, 0.98) 1.04 (0.88, 1.22) p-inter = 0.0396 0.72 (0.50, 1.02) 0.86 (0.68, 1.09) p-inter = 0.3930 0.50 (0.27, 0.92) 0.38 (0.24, 0.62) p-inter = 0.5395 0.88 (0.79, 0.99) 0.92 (0.85, 0.98) p-inter = 0.6174
Arrhythmias and Clinical EP CLINICAL OUTCOMES OF ATRIAL FIBRILLATION PATIENTS RECEIVING DIGOXIN IN THE RE-LY® TRIAL Poster Contributions Poster Area, South Hall A1 Sunday, April 03, 2016, 9:45 a.m.-10:30 a.m. Session Title: Can Trials Help Us Better Treat Atrial Fibrillation? Abstract Category: 16. Arrhythmias and Clinical EP: AF/SVT Presentation Number: 1188-351 Authors: Rangadham Nagarakanti, Stuart Connolly, Mandy Fraessdorf, Martina Brueckmann, Joerg Kreuzer, Paul Reilly, Jonas Oldgren, Salim Yusuf, Lars Wallentin, Michael Ezekowitz, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA Background: Safety and efficacy of dabigatran etexilate (DE) vs warfarin was compared in RE-LY patients with or without digoxin at baseline and during follow up.
Methods: Baseline characteristics were compared by Fisher’s exact- or t-test. Event rates were reported for subgroups and treatment. Cox regression hazards models provided hazard ratios.
Results: Of 18,113 patients, 29% on DE or warfarin received digoxin at baseline. Of 6173 patients who received digoxin at least once, 5329 received it >50 to ≤100% of the time and 844 received it ≤50% of the time. Patients on digoxin (vs none) were younger, more often had heart failure (HF), valvular heart disease and diabetes, but less often coronary artery disease (all p < 0.0001). CHADS2 scores were slightly higher in digoxin users (2.2 vs 2.1; p < 0.0001). In patients with digoxin >50 to ≤100% of time vs no digoxin, there was higher rate of stroke and systemic embolism (SSE) (p <0.0001), ischemic stroke (p = 0.0002) and risk of death (p < 0.0001) (Table), even after multivariate adjustment for covariates. Rates of hospitalization, intracranial and major bleeds were similar with digoxin vs none. Irrespective of digoxin use, benefits of DE vs warfarin were similar in terms of SSE, major, life-threatening or intracranial bleeds (Table). Conclusions: Digoxin use was associated with higher risk of death and stroke vs non-use. Irrespective of digoxin use, patients derived similar relative benefits of DE indicating no adverse drug interaction on clinical outcomes. Table: Treatment effects of dabigatran vs. warfarin Digoxin use
Annual rate Dabigatran 110 mg bid
Annual rate Dabigatran 150 mg bid
Annual rate Warfarin
Digoxin at baseline; No Digoxin at baseline
2.04 1.33
1.32 1.04
2.10 1.57
Stroke + Systemic embolism Digoxin during treatment
Never used Digoxin Digoxin during study (0 to ≤50%); Digoxin during study (50 to ≤100%); Digoxin always (100%)
1.28 1.39 2.12 1.85
0.91 1.66 1.51 1.22
1.46 3.44 2.04 2.02
Haemorrhagic stroke
Digoxin at baseline No Digoxin at baseline
0.17 0.10
0.17 0.07
0.47 0.35
Death
Digoxin at baseline No Digoxin at baseline
4.85 3.29
4.54 3.27
5.86 3.42
MI (including silent)
Digoxin at baseline No Digoxin at baseline
0.94 0.78
1.06 0.70
0.67 0.62
Major bleed
Digoxin at baseline No Digoxin at baseline
3.12 2.83
3.38 3.45
4.29 3.33
Life-threatening bleed
Digoxin at baseline No Digoxin at baseline
1.59 1.13
1.52 1.52
2.13 1.77
Intracranial haemorrhage
Digoxin at baseline No Digoxin at baseline
0.28 0.20
0.43 0.28
0.88 0.73
Any bleeding
Digoxin at baseline No Digoxin at baseline
14.05 15.09
15.55 17.02
17.74 18.66
Outcome (ITT) Stroke + Systemic embolism Digoxin at baseline
DE 110 mg vs. warfarin HR (95% CI)
DE 150 mg vs. warfarin HR (95% CI)
0.97 (0.70, 1.35) 0.85 (0.66, 1.09) p-inter = 0.5234 0.88 (0.67, 1.15) 0.40 (0.17, 0.91) 1.05 (0.76, 1.45) 0.92 (0.63, 1.32) p-inter (0 - ≤50% vs. never) = 0.0733 p-inter (50 to ≤100% vs. never) = 0.4340 p-inter (always vs. never) = 0.8757 0.37 (0.14, 0.94) 0.27 (0.13, 0.60) p-inter = 0.6634 0.82 (0.67, 1.01) 0.96 (0.81, 1.13) p-inter = 0.2510 1.40 (0.82, 2.39) 1.25 (0.87, 1.80) p-inter = 0.7414 0.72 (0.56, 0.93) 0.85 (0.71, 1.01) p-inter = 0.2949 0.75 (0.53, 1.06) 0.64 (0.49, 0.83) p-inter = 0.4971 0.33 (0.16, 0.67) 0.28 (0.16, 0.47) p-inter = 0.7480 0.78 (0.69, 0.88) 0.78 (0.73, 0.84) p-inter = 0.9767
0.63 (0.43, 0.91) 0.66 (0.51, 0.87) p-inter = 0.8138 0.62 (0.46, 0.83) 0.48 (0.22, 1.03) 0.74 (0.52, 1.06) 0.60 (0.39, 0.91) p-inter (0 - ≤50% vs. never) = 0.5364 p-inter (50 to ≤100% vs. never) = 0.4492 p-inter (always vs. never) = 0.8961 0.37 (0.15, 0.95) 0.20 (0.08, 0.49) p-inter = 0.3582 0.77 (0.63, 0.95) 0.96 (0.81, 1.13) p-inter = 0.1076 1.60 (0.95, 2.69) 1.13 (0.78, 1.63) p-inter = 0.2930 0.76 (0.60, 0.98) 1.04 (0.88, 1.22) p-inter = 0.0396 0.72 (0.50, 1.02) 0.86 (0.68, 1.09) p-inter = 0.3930 0.50 (0.27, 0.92) 0.38 (0.24, 0.62) p-inter = 0.5395 0.88 (0.79, 0.99) 0.92 (0.85, 0.98) p-inter = 0.6174