No Influence on Cardiac Arrhythmia or Heart Rate from Long-Term Treatment with Tiotropium/Olodaterol versus Monocomponents by Holter ECG Analysis in Patients with Moderate-to-Very-Severe COPD

Figures & data

Table 1 Baseline Demographics of Holter ECG Subgroup (TONADO 1 and 2)

Characteristics	Olo 5 µg (n=179)	Tio 5 µg (n=181)	T/O 5/5 µg (n=146)
Male, n (%)	119 (66.5)	112 (61.9)	93 (63.7)
Age, mean (SD), years	64.4 (7.7)	63.5 (8.8)	63.1 (8.2)
Smoking status, n (%)
Ex-smoker	105 (58.7)	96 (53.0)	74 (50.7)
Current smoker	74 (41.3)	85 (47.0)	72 (49.3)
BMI, mean (SD), kg/m^2	27.4 (6.1)	26.7 (4.9)	26.6 (5.5)
FEV1% predicted normal, mean (SD)	43.1 (15.0)	44.9 (16.0)	42.7 (14.1)
Spirometric GOLD grades, n (%)
1 (≥80%)	0 (0.0)	1 (0.6)	0 (0.0)
2 (50% to <80%)	88 (49.2)	104 (57.5)	66 (45.2)
3 (30% to <50%)	67 (37.4)	50 (27.6)	68 (46.6)
4 (<30%)	24 (13.4)	26 (14.4)	12 (8.2)
Mean Holter heart rate	79.3 (9.5)	80.3 (11.3)	82.5 (11.2)
Any cardiovascular disease	102 (57.0)	104 (57.5)	81 (55.5)
Cardiac arrhythmia	25 (14.0)	22 (12.2)	15 (10.3)
Tachyarrhythmia (tachycardia)	9 (5.0)	5 (2.8)	8 (5.5)
Supraventricular tachyarrhythmia	4 (2.2)	2 (1.1)	6 (4.1)
Atrial fibrillation or flutter	4 (2.2)	2 (1.1)	5 (3.4)
Ventricular tachyarrhythmia (ventricular arrhythmia)	3 (1.7)	0 (0.0)	2 (1.4)
Bradyarrhythmia (bradycardia)	5 (2.8)	10 (5.5)	5 (3.4)
Ischemic heart disease^a	27 (15.1)	22 (12.2)	19 (13.0)
Myocardial infarction^b	8 (4.5)	11 (6.1)	8 (5.5)
Cardiac failure	11 (6.1)	4 (2.2)	5 (3.4)
Cerebrovascular disorders	15 (8.4)	11 (6.1)	6 (4.1)
Hypertension	81 (45.3)	89 (49.2)	68 (46.6)
Diabetes mellitus	23 (12.8)	23 (12.7)	20 (13.7)
Any cardiovascular medication	120 (67.0)	109 (60.2)	85 (58.2)
Beta-blockers	20 (11.2)	22 (12.2)	16 (11.0)

Notes: ^aIncludes angina pectoris, arteriosclerosis coronary artery, blood creatinine phosphokinase increase, coronary angioplasty, coronary arterial stent insertion, coronary artery bypass, coronary artery disease, coronary artery occlusion, coronary artery stenosis, infarction, ischemic cardiomyopathy, myocardial infarction, myocardial ischemia and stress cardiomyopathy; ^bIncludes conditions attributed to infarction, including blood creatinine phosphokinase increase, coronary artery occlusion and infarction.

Abbreviations: BMI, body mass index; ECG, electrocardiogram; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; Olo, olodaterol; SD, standard deviation; T/O, tiotropium/olodaterol; Tio, tiotropium.

Figure 1 (A) Shifts in SVPB: T/O vs monocomponents at Week 12 (TONADO 1 and 2), and (B) shifts in VPB: T/O vs monocomponents at Week 12 (TONADO 1 and 2). P-value based on Chi-squared test: no statistical difference in frequency of increase or decrease.

Abbreviations: Olo, olodaterol; SVPB, supraventricular premature beat; T/O, tiotropium/olodaterol; Tio, tiotropium; VPB, ventricular premature beat. For definition of shifts in SVPB and VPB, see Methods section (Sub-analyses on Holter ECGs).

Figure 2 Adjusted mean Holter heart rate over 24 hours at Week 12: T/O vs monocomponents at baseline and Week 12 (TONADO 1 and 2). Treated set: adjusted data. Baseline data are unadjusted. P-values are for adjusted mean change from baseline data. Standard errors for baseline are 0.71, 0.84 and 0.93, respectively, and for week 12 were 0.53, 0.53 and 0.72, respectively.

Abbreviations: bpm, beats per minute; Olo, olodaterol; T/O, tiotropium/olodaterol; Tio, tiotropium.

Table 2 Cardiovascular Adverse Events of Holter ECG Subgroup (TONADO 1 and 2)

Patients, n (%)	Olo 5 µg (n=179)	Tio 5 µg (n=181)	T/O 5/5 µg (n=146)
Cardiac arrhythmia
Supraventricular tachyarrhythmia	1 (0.6)	2 (1.1)	0 (0.0)
Atrial fibrillation or flutter	1 (0.6)	1 (0.6)	0 (0.0)
Ventricular tachyarrhythmia	2 (1.1)	0 (0.0)	1 (0.7)
Ischemic heart disease
Myocardial infarction	0 (0.0)	1 (0.6)	1 (0.7)
Other ischemic heart disease (non-infarction)	4 (2.2)	1 (0.6)	1 (0.7)
Cardiac failure	2 (1.1)	3 (1.7)	0 (0.0)
Cerebrovascular disorders
Hemorrhagic	0 (0.0)	0 (0.0)	0 (0.0)
Ischemic	0 (0.0)	0 (0.0)	1 (0.7)
MACE	1 (0.6)	2 (1.1)	3 (2.1)
Fatal MACE (including death unspecified)	1 (0.6)	1 (0.6)	2 (1.4)

Abbreviations: ECG, electrocardiogram; MACE, major adverse cardiovascular events (including cardiac disorders, vascular disorders, myocardial infarction, stroke and fatal MACE; sudden death, cardiac death and sudden cardiac death); Olo, olodaterol; T/O, tiotropium/olodaterol; Tio, tiotropium.