A Post Hoc Holter ECG Analysis of Olodaterol and Formoterol in Moderate-to-Very-Severe COPD

Figures & data

Table 1 Baseline Demographics of Holter ECG Subgroups (1222.11, 1222.12, 1222.13 and 1222.14)

Characteristics	Placebo (N=226)	Olo 5 µg (N=235)	Olo 10 µg (N=234)	Form 12 µg (N=80)
Male, n (%)	150 (66.4)	163 (69.4)	157 (67.1)	60 (75.0)
Age, mean (SD), years	63.9 (7.9)	62.8 (8.5)	62.8 (8.6)	62.5 (8.8)
Smoking status, n (%)  Ex-smoker  Current smoker	125 (55.3) 101 (44.7)	131 (55.7) 104 (44.3)	128 (54.7) 106 (45.3)	46 (57.5) 34 (42.5)
BMI, mean (SD), kg/m^2	26.2 (6.4)	27.4 (6.8)	26.2 (6.4)	24.0 (5.2)
FEV1% predicted normal, mean (SD)	46.4 (15.0)	44.6 (14.4)	44.4 (15.3)	44.3 (15.1)
GOLD stage, n (%)  1 (≥80%)  2 (50% to <80%)  3 (30% to <50%)  4 (<30%)	1 (0.4) 132 (58.4) 74 (32.7) 19 (8.4)	1 (0.4) 119 (50.6) 98 (41.7) 17 (7.2)	1 (0.4) 114 (48.7) 102 (43.6) 17 (7.3)	0 (0.0) 40 (50.0) 32 (40.0) 8 (10.0)
Holter heart rate, mean (SD)	81.0 (9.7)	81.1 (10.2)	82.2 (11.4)	82.2 (11.7)
Cardiovascular disease, n (%)	129 (57.1)	147 (62.6)	147 (62.8)	39 (48.8)
Cardiac arrhythmia, n (%)  Tachyarrhythmia (tachycardia)  Supraventricular tachyarrhythmia  Atrial fibrillation or flutter  Ventricular tachyarrhythmia (ventricular arrhythmia)  Bradyarrhythmia (bradycardia)	41 (18.1) 21 (9.3) 8 (3.5) 7 (3.1) 13 (5.8) 19 (8.4)	45 (19.1) 23 (9.8) 4 (1.7) 3 (1.3) 18 (7.7) 21 (8.9)	40 (17.1) 21 (9.0) 6 (2.6) 4 (1.7) 17 (7.3) 21 (9.0)	9 (11.3) 3 (3.8) 1 (1.3) 0 (0.0) 1 (1.3) 5 (6.3)
Ischemic heart disease^a, n (%)  Myocardial infarction^b  Other ischemic heart disease (non-infarction)	28 (12.4) 11 (4.9) 23 (10.2)	35 (14.9) 11 (4.7) 30 (12.8)	42 (17.9) 11 (4.7) 37 (15.8)	7 (8.8) 3 (3.8) 6 (7.5)
Cardiac failure, n (%)	6 (2.7)	5 (2.1)	9 (3.8)	1 (1.3)
Cerebrovascular disorders, n (%)	9 (4.0)	10 (4.3)	11 (4.7)	1 (1.3)
Hypertension, n (%)	94 (41.6)	122 (51.9)	107 (45.7)	29 (36.3)
Diabetes mellitus, n (%)	27 (11.9)	40 (17.0)	33 (14.1)	8 (10.0)
Cardiovascular medication, n (%)
Any cardiovascular medication^c	151 (66.8)	171 (72.8)	168 (71.8)	47 (58.8)
β−blockers	34 (15.0)	35 (14.9)	24 (10.3)	5 (6.3)
Other cardiovascular medication^d	151 (66.8)	170 (72.3)	165 (70.5)	46 (57.5)
Respiratory medications, n (%)
SAMA	56 (24.8)	49 (20.9)	52 (22.2)	17 (21.3)
LAMA	67 (29.6)	67 (28.5)	71 (30.3)	25 (31.3)
SABA	133 (58.8)	102 (43.4)	108 (46.2)	34 (42.5)
LABA	93 (41.2)	136 (57.9)	141 (60.3)	40 (50.0)
ICS	105 (46.5)	110 (46.8)	110 (47.0)	35 (43.8)

^aIncludes angina pectoris, arteriosclerosis coronary artery, blood creatinine phosphokinase increase, coronary angioplasty, coronary arterial stent insertion, coronary artery bypass, coronary artery disease, ECG T wave abnormal, ECG T wave inversion, ischemic cardiomyopathy, myocardial infarction, myocardial ischemia and silent myocardial infarction; ^bIncludes conditions attributed to infarction, including blood creatinine phosphokinase increase, myocardial infarction and silent myocardial infarction; ^cIncludes β-blockers and other cardiovascular medication; ^dAgents acting on the renin-angiotensin system, antihypertensives, antithrombotic agents, calcium channel blockers, diuretics, lipid-modifying agents, other cardiac therapy, peripheral vasodilators and vasoprotectives.

Abbreviations: BMI, body mass index; ECG, electrocardiogram; FEV₁, forced expiratory volume in 1 second; Form, formoterol; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; Olo, olodaterol; SABA, short-acting β₂-agonist; SAMA, short-acting muscarinic antagonist; SD, standard deviation.

Figure 1 Shifts in SVPB: olodaterol and formoterol vs placebo at (A) Week 12, (B) Week 24, (C) Week 40 and (D) Week 48.

P-values for overall differences between category of change and category of treatment calculated by Chi-squared frequency tests; Numbers above the bars are % of patients whereas numbers within the bars are number of patients.

Abbreviations: Form, formoterol; Olo, olodaterol; SVPB, supraventricular premature beats.

Figure 2 Shifts in VPB: olodaterol and formoterol vs placebo at (A) Week 12, (B) Week 24, (C) Week 40 and (D) Week 48.

P-values for overall differences between category of change and category of treatment calculated by Chi-squared frequency tests; Numbers above the bars are % of patients whereas numbers within the bars are number of patients.

Abbreviations: Form, formoterol; Olo, olodaterol; VPB, ventricular premature beats.

Figure 3 Unadjusted baseline heart rate (A) and adjusted mean change in heart rate from baseline (B): olodaterol and formoterol vs placebo during treatment. *P<0.05. P-values are for adjusted mean change from baseline.

Abbreviations: bpm, beats per minute; Form, formoterol; Olo, olodaterol; SD, standard deviation; SE, standard error.

Table 2 Adverse Events of Holter ECG Subgroups

Patients, n (%)	Placebo (N=226)	Olo 5 µg (N=235)	Olo 10 µg (N=234)	Form 12 µg (N=80)
Cardiac arrhythmia
Supraventricular tachyarrhythmia	9 (4.0)	4 (1.7)	5 (2.1)	4 (5.0)
Atrial fibrillation or flutter	6 (2.7)	2 (0.9)	3 (1.3)	1 (1.3)
Ventricular tachyarrhythmia	8 (3.5)	15 (6.4)	12 (5.1)	7 (8.8)
Ischemic heart disease
Myocardial infarction	5 (2.2)	2 (0.9)	8 (3.4)	1 (1.3)
Other ischemic heart disease (non-infarction)	4 (1.8)	3 (1.3)	6 (2.6)	0 (0.0)
Cardiac failure	1 (0.4)	1 (0.4)	1 (0.4)	1 (1.3)
Cerebrovascular disorders  Hemorrhagic  Ischemic	1 (0.4) 3 (1.3)	1 (0.4) 3 (1.3)	0 (0.0) 2 (0.9)	0 (0.0) 0 (0.0)
MACE	9 (4.0)	5 (2.1)	8 (3.4)	2 (2.5)
Fatal MACE (including death unknown)	2 (0.9)	2 (0.9)	1 (0.4)	1 (1.3)

Abbreviations: ECG, electrocardiogram; Form, formoterol; MACE, major adverse cardiovascular events (including cardiac disorder, vascular disorders, myocardial infarction, stroke, sudden death, cardiac death and sudden cardiac death); Olo, olodaterol.