Determinants of Long-Term Persistence with Tiotropium Bromide for Chronic Obstructive Pulmonary Disease

Figures & data

Table 1.  Characteristics of the study groups

	Tiotropium bromide			P
	Prescribed (n = 255)		Not prescribed (n = 389)
Men	224 (88)		339 (87)	ns
Age, y	72 ± 8		67 ± 10	<0.05
Body mass index, kg/m^2	22.7 ± 3.4		23.5 ± 3.4	<0.05
Smoking history
Current smoker,	96 (38)		127 (33)	ns
Pack-year	67 ± 44		54 ± 32	<0.05
Respiratory disease manifestations
Sputum production	114 (45)		137 (35)	<0.05
Cough	111 (44)		156 (40)	ns
Modified Medical Research Council dyspnea scale	1.7 ± 1.0		0.9 ± 0.9	<0.05
Pulmonary function
Vital capacity,% predicted	94 ± 18		99±19	<0.05
Forced expiratory volume in 1 sec
% predicted	58 ± 20		72 ± 18	<0.05
^3 80%	33 (13)		143 (37)
50–79%	123 (48)		206 (53)
30–49%	62 (24)		33 (8)
<30%	37 (15)		7 (2)
Forced expiratory volume in 1 sec / forced vital  capacity,%	49±13		60 ± 9	<0.05
Carbon monoxide diffusing capacity/alveolar volume,%  predicted	59 ± 22 (n = 129)		75 ± 23 (n = 111)	<0.05
Emphysema score, 0–24	9.9 ± 5.9 (n = 228)		5.2 ± 4.7 (n = 277)	<0.05
Long-term oxygen therapy	38 (15)		11 (3)	<0.05

Values are numbers (%) of observations or means ± standard deviations; ns = not significant.

Figure 1. Flow of patients from initial screening to the final study group assignments.

Table 2.   Single variable logistic regression analysis of the factors correlated with continuation of tiotropium bromide beyond 1 year after its introduction

	Tiotropium bromide			OR (95% CI)	P
	Continued (n = 190)		Discontinued (n = 48)
Men	168 (88)		42 (88)	0.92 (0.35–2.40)	ns
Age, y	73 ± 8		69 ± 9	0.94 (0.90–0.98)	0.001
Body mass index, kg/m^2	22.7 ± 3.3		22.8 ± 3.7	1.01 (0.92–1.11)	ns
Smoking history Current smoker  Pack-year	62 (33) 68±45		28 (58) 64 ± 44	0.35 (0.18–0.66) 1.00 (0.99–1.01)	0.001 ns
Respiratory disease manifestations Sputum production  Cough
	88 (46)		19 (40)	1.32 (0.69–2.51)	ns
	88 (46)		17 (35)	1.58 (0.82–3.03)	ns
Modified Medical Research Council dyspnea scale	1.7±1.0		1.6 ± 1.0	1.05 (0.80–1.37)	ns
Adverse effects	3 (1.6)		13 (27.1)	0.04 (0.01–0.16)	<0.001
Disease exacerbation
In year preceding treatment,	44 (23)		9 (19)	1.31 (0.59–2.90)	ns
Within 1 year after initiation of treatment	40 (21)		3 (6)	4.00 (1.18–13.5)	0.03
Pulmonary function tests
Vital capacity,% predicted	95 ± 19		93 ± 15	0.99 (0.98–1.01)	ns
Forced expiratory volume in 1 sec,% predicted	56 ± 21		62 ± 16	1.02 (0.99–1.03)	ns
Forced expiratory volume in 1 sec  <50% of predicted	83 (44)		9 (19)	3.36 (1.54–7.33)	0.002
Forced expiratory volume in 1 sec / forced vital  capacity,%	47 ± 13		54 ± 10	1.05 (1.02–1.08)	0.001
Carbon monoxide diffusing capacity / alveolar volume,%  predicted	58 ± 22 (n = 109)		65 ± 22 (n = 17)	1.01 (0.99–1.04)	ns
Emphysema score	10.5 ± 5.7 (n = 173)		7.9 ± 5.9 (n = 55)	0.92 (0.86–0.98)	0.01 0.002
None/Mild, 0–2	18 (10)		11 (20)
Moderate, 3–6	32 (18)		16 (29)
Severe, 7–12	59 (34)		13 (24)
Very severe, 13–24	64 (37)		15 (27)
Prior drug therapy
Long-acting  b2 adrenergic agonist	51 (27)		10 (21)	1.18 (0.59–2.34)	ns
Inhaled corticosteroid	37 (19)		10 (21)	1.13 (0.53–2.39)	ns
Respiratory symptom alleviation in response to tiotropium bromide	84 (44)		9 (19)	3.43 (1.58–7.49)	0.002
Long-term oxygen therapy	31 (16)		4 (8)	2.15 (0.72–6.40)	ns

Values are numbers (%) of observations or means ± standard deviations; CI = confidence interval, ns = not significant.

Table 3.   Multiple variable logistic regression analysis of the factors correlated with continuation of treatment with tiotropium bromide beyond 1 year after its introduction

	Odds ratio (95% CI)	P
Current smoking	0.28 (0.13–0.60)	0.001
Forced expiratory volume in 1 sec <50% of predicted	2.54 (1.08–5.97)	0.033
Respiratory symptom alleviation in response to tiotropium bromide	2.28 (0.99–5.29)	0.054
Adverse effects	0.04 (0.01–0.18)	<0.001
Disease exacerbation during 1st year of treatment	3.18 (0.84—12.0)	0.089

CI = confidence interval.

Figure 2. Kaplan–Meier estimates of cumulative probability of discontinuation of tiotropium bromide in 255 patients.

Figure 3. Kaplan–Meier estimates of cumulative probability of discontinuation of tiotropium bromide according to a) former versus current smoker status, b) ≥50% versus <50% FEV₁, c) alleviation versus no alleviation of symptoms, and d) exacerbation versus no exacerbation of COPD during first year of treatment with tiotropium bromide. The p-values were calculated by log-rank test.

Table 4.   Cox proportional hazards regression analysis of factors correlated with continuation of treatment with tiotropium bromide beyond 1 year

	Hazard ratio (95% CI)	p
Current smoking	0.52 (0.31–0.87)	0.013
Forced expiratory volume in 1 sec < 50% of predicted	1.35 (1.00–1.82)	0.052
Adverse effects	0.11 (0.06–0.21)	<0.001
Disease exacerbation during 1st year of treatment	3.37 (1.05–10.9)	0.042

CI = confidence interval.