Eletrocardiographic Monitoring in COPD Patients Receiving Tiotropium

Figures & data

Table 1.  ECG Changes Reported as Adverse Events in the 12‐Month and the Six‐Month Studies

	12‐Month studies				6‐Month studies
	Tiotropium		Placebo		Tiotropium		Salmeterol		Placebo
	n	%	n	%	n	%	n	%	n	%
Total treated	550	(100.0)	371	(100.0)	402	(100.0)	405	(100.0)	400	(100.0)
Total with any ECG adverse event	5	(0.9)	9	(2.4)	8	(2.0)	8	(2.0)	3	(0.7)
Extrasystoles	0	(0.0)	0	(0.0)	2	(0.5)	2	(0.5)	2	(0.5)
Atrial fibrillation	0	(0.0)	2	(0.5)	2	(0.5)	1	(0.2)	0	(0.0)
Multifocal atrial tachycardia	1	(0.2)	0	(0.0)	0	(0.0)	0	(0.0)	0	(0.0)
Sinus tachycardia	0	(0.0)	0	(0.0)	0	(0.0)	0	(0.0)	0	(0.0)
Myocardial infarction	0	(0.0)	2	(0.5)	2	(0.5)	2	(0.5)	0	(0.0)
Other changes	4	(0.7)	5	(1.5)	2	(0.5)	3	(0.7)	1	(0.2)

Table 2.  ECG Monitoring in the 12‐Month Placebo Studies

	Tiotropium	Placebo
Patients (n)	518	343
Heart rate
Mean change (bpm)	0.1	− 0.1
Maximum change (bpm)	6.7	6.2
% with bradycardia events	0.8	1.2
% with tachycardia events	2.5	2.0
PR
Mean change (msec)	1.2	1.0
% outliers	0.2	0.9
QRS
Mean change (msec)	1.0	0.1
% outliers	1.2	0.6
QT
Mean change (msec)	0.4	–0.1
% New QT > 500 msec	0	0
QTc by Bazett
Mean change (msec)	1.0	–0.2
Maximum change (msec)	14.3	13.1
% New QTcB > 500 msec	0.8	0.3
% Change of 30–60 msec	21.3	22.2
% Change > 60 msec	2.7	1.5
QTc by Fridericia
Mean change (msec)	0.6	− 0.3
Maximum change (msec)	11.8	11.1
% New QTcB > 500 msec	0.2	0.3
% Change of 30–60 msec	14.7	15.2
% Change > 60 msec	1.4	0.3

*Varies according to ability to characterize each parameter.

Table 3.  ECG Monitoring in the 6‐Month Salmeterol and Placebo‐Controlled Trials

	Tiotropium	Salmeterol	Placebo
Patients (n)	346	338	315
Heart rate
Mean change (bpm)	2.6	1.3	1.7
% with bradycardia events	0.9	0.3	0
% with tachycardia events	1.4	1.2	1.6
PR
Mean change (msec)	1.6	− 0.3	0.8
% Outliers	0.6	0	0.3
QRS
Mean change (msec)	1.4	0.5	0.3
% Outliers	1.4	0.6	0.3
QT
Mean change (msec)	− 4.5	− 1.7	− 4.0
% New QT > 500 msec	0	0	0
QTc by Bazett
Mean change (msec)	2.0	2.1	0.4
% New QTcB > 500 msec	0	0	0
% Change of 30–60 msec	9.0	9.8	9.2
% Change > 60 msec	1.4	2.4	1.0
QTc by Fridericia
Mean change (msec)	− 0.3	0.8	− 1.2
% New QTcF > 500 msec	0	0	0
% Change of 30–60 msec	6.4	6.8	5.1
% Change > 60 msec	0.3	0.9	0.3

*Varies according to ability to characterize each parameter.

Table 4.  Changes in Heart Rate, Rhythm or Conduction Observed in the Multidose Dose‐Ranging Study.

	Tiotropium bromide				Placebo
	4.5 mcg	9 mcg	18 mcg	36 mcg
Total patients treated (n)	34	33	33	34	35
Total patients with changes (n)	24	22	23	16	20
Borderline PR interval	0	1	0	0	1
First degree A‐V block	1	0	1	0	1
Atrial fibrillation	0	1	0	0	0
Sinus arrhythmia	0	0	0	1	0
Sinus tachycardia	0	0	1	0	1
Consistent with ventricular tachycardia	1	0	0	0	0
Repetitive premature systoles	2	0	2	0	1
Multiform premature systoles	4	2	1	2	0
Premature systoles, ventricular	11	7	10	8	9
Premature systoles, atrial	10	10	10	6	10
Sinus arrest or sino‐atrial block	2	2	0	0	0
Ectopic atrial rhythm	0	2	1	0	2
Borderline QT interval	0	0	1	0	1

*The numbers indicate the number of patients who had the associated abnormality on any ECG while on treatment.

Table 5.  Holter Monitoring Summary for Heart Rate and Number of Patients with Supraventricular Tachycardia (SVT) and Ventricular Tachycardia (V Tach)

		Tiotropium AM (n = 37)		Tiotropium PM (n = 35)		Placebo (n = 31)
		Baseline	6 Weeks	Baseline	6 Weeks	Baseline	6 Weeks
Heart rate (beats/min)	Mean	76	78	73	74	77	78
	Min/max	61/108	61/109	57/106	58/104	62/111	60/110
SVT	# Patients	7	7	5	5	3	7
V tach	# Patients	1	2	1	2	2	1
	Longest run	20	6	12	6	6	5