Update 2014:
COPD
Kenneth R. Chapman
Professor of Medicine
University of Toronto
Disclosures
Consultations
Almirall, Baxter,
CSL Behring,
Forest Labs,
GlaxoSmithKline,
Merck Frosst,
Novartis,
Nycomed, Pfizer,
Roche, Schering
Plough, Grifols
Research
Grants/Contracts
Amgen, AstraZeneca,
CSL Behring, Forest
Labs, Genentech,
GlaxoSmithKline,
Novartis, Nycomed,
Parangenix, Roche,
Schering, Grifols
Lectures
AstraZeneca,
BoehringerIngelheim, Grifols,
GlaxoSmithKline,
Merck Frosst,
Novartis,
Nycomed, Pfizer,
Grifols
Objectives of the
Presentation
•
•
Review the changing epidemiology of COPD
in Canada.
Review the challenge of COPD diagnosis.
Objectives (cont’d)
•
Review critically the treatments available for
COPD and ask:
•
•
•
•
•
Are long acting beta2 agonists safe in
COPD?
Are anticholinergic bronchodilators preferred
in COPD?
Are anticholinergic bronchodilators safe in
COPD?
Have we overused ICS in COPD?
Are self-management plans helpful or
harmful in COPD?
The Evolving
Epidemiology of
COPD
The effect on mortality of decreased
tobacco consumption
Proportion of 1965 rate
3.0
2.5
2.0
Coronary
heart
disease
Stroke
Other
CVD
COPD
All other
causes
–59%
–64%
–35%
+163%
–7%
1.5
1.0
0.5
0
Percentage change in age-adjusted death rates in USA, from 1965 to 1998
CVD = cerebrovascular disease
www.copdgold.com
COPD Mortality in Canada: 1950 to 2010
More Canadian women will
die this year as the result of
COPD than will die as the
result of breast cancer.
Number of Patients
COPD: The Leading Cause of
Hospital Admissions Today
18,000
Single Hospitalization
1 Repeat Hospitalization
2 or More Repeat Hospitalizations
16,000
14,000
12,000
10,000
8,000
6,000
4,000
2,000
0
COPD
Angina
Asthma Heart Failure Diabetes
Epilepsy
Ambulatory Care Sensitive Condition*
*An ambulatory care sensitive condition is a condition that is normally manageable on an outpatient basis
Data are for the Canadian population, excluding QuebecCIHI. Health Indicators 2008.
COPD is Underdiagnosed:
Screening Spirometry in Primary Practice
•
Patients >40 yrs + 20 pack-year history of smoking
visiting a primary care physician for any reason.
Spirometry
results
Normal
70.3%
Criteria
for COPD
20.7%
Previously
Diagnosed
33%
Previously
Undiagnosed
67%
Hill K, et al. CMAJ 2010182:673-678
COPD is Over-Diagnosed
Misclassification in Primary Care
Percentage of Patients Diagnosed with COPD
Who Do Not Meet Spirometric Criteria for COPD
The Cost of Misdiagnosis
Per Month
Per Year
Advair Diskus 250/50
$ 124.96
$ 1499.52
Advair Diskus 500/50
$ 171.10
$ 2053.20
Ventolin MDI 100 ug
$ 19.84
$ 238.08
Triple Therapy
$ 279.92
$ 3359.40
Spirometry (Pre/Post Bronchodilator)
Spiriva 18 ug
$ 89.01
$ 1068.12
$ 24.16
COPD and CHF in Tertiary Care:
Eight Year Record of Diagnostic Testing
COPD
CHF
29% of COPD patients did not have
obstruction on spirometry
Damarla M et al. 2006. Respir Care
Real Doctors Don’t Use Spirometry
Treatment Plans
Optimal Pharmacotherapy in COPD
Increasing Disability and Lung Function Impairment
Mild
Moderate
SABA prn
persistent
disability
LAAC + SABA prn
or
LABA + SABA prn
Severe
Infrequent AECOPD
Frequent AECOPD
(< 1/year)
(> 1/year)
LAAC or LABA+ SABA prn
LAAC + ICS/LABA +
SABA prn
persistent
disability
LAAC + LABA + SABA
prn persistent
disability
LAAC + ICS/LABA* +
SABA prn
persistent
disability
LAAC + ICS/LABA +
SABA prn +/- Theophylline
* Inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) combination with the lower ICS
dose i.e. SALM/FP 50/250 µg twice daily
O’Donnell DE, et al. Can Respir J 2007
Optimal Pharmacotherapy in COPD
Increasing Disability and Lung Function Impairment
Mild
Moderate
SABA prn
persistent
disability
LAAC + SABA prn
or
LABA + SABA prn
Severe
Infrequent AECOPD
Frequent AECOPD
(< 1/year)
(> 1/year)
LAAC or LABA+ SABA prn
LAAC + ICS/LABA +
SABA prn
persistent
disability
LAAC + LABA + SABA
prn persistent
disability
LAAC + ICS/LABA* +
SABA prn
persistent
disability
LAAC + ICS/LABA +
SABA prn +/- Theophylline
* Inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) combination with the lower ICS
dose i.e. SALM/FP 50/250 µg twice daily
O’Donnell DE, et al. Can Respir J 2007
Optimal Pharmacotherapy in COPD
Increasing Disability and Lung Function Impairment
Moderate
Severe
Infrequent AECOPD
Frequent AECOPD
(< 1/year)
(> 1/year)
LAAC or LABA
LAAC + ICS/LABA
LAAC + ICS/LABA
LAAC + ICS/LABA
+/- Theophylline
O’Donnell DE, et al. Can Respir J 2007
Tio
Tio + ICS/LABA
ICS/LABA
ICS/LABA + Tio
Evaluating COPD
severity
Treatable. Preventable.
A Comprehensive
Approach to COPD
Management
Surgery
Surgery
Oxygen
Inhaled
Inhaled corticosteroids
corticosteroids/LABA
Pulmonary rehabilitation
Long
Long-acting bronchodilator(s)
PRN
PRNRapid
short-acting bronchodilators
Smoking
Smokingcessation/exercise/self
cessation/exercise/self-management/education
Lung function
impairment
Mild
Very Severe
MRC Dyspnea
II
V
Early Diagnosis
(Spirometry) +
Prevention
Prevent/Rx AECOPD
Follow-up
O’Donnell DE, et al. Can Resp J 2007; 14:5B-32B
End of Life
Care
Lung Function and Symptoms:
Both Are Tied to Outcomes
Survival by
Level of Dyspnea
100
Stage I (n=42)
Stage II (n=59)
80
60
Stage III (n=82)
40
20
p = 0.08
0
0
10
20
30 40
50
Months of Follow-Up
Nishimura K, et al.: Chest 2002; 121(5):1434-40.
60
70
Cumulative Percent Survival (%)
Cumulative Percent Survival (%)
Survival by ATS Stage
(based on FEV1)
100
Grade II (n=67)
80
Grade III (n=87)
60
40
Grade IV (n=26)
20
p < 0.001
Grade V (n=3)
0
0
10
20
30 40
50
Months of Follow-Up
60
70
(C)
(D)
>2
(A)
(B)
1
3
2
1
0
mMRC 0-1
CAT < 10
mMRC > 2
CAT > 10
Symptoms
(mMRC or CAT score))
(Exacerbation history)
4
Risk
(GOLD Classification of Airflow Limitation)
Risk
Combined Assessment of COPD
Treatment Options
for Mild, Moderate
COPD
Long-acting
Antimuscarinics
(LAMA’s)
Tiotropium vs Ipratropium: 3 month
FEV1 Response
Day 1
Day 8
FEV1 (L)
Day 92
Tiotropium (n=182)
Ipratropium (n=93)
-60
-5
30
60
120
180
240
300
360
Time after Administration (minutes)
Van Noord JA et al. Thorax
2000
Probability of No Hospitalization
Tiotropium: Delayed Onset of First
Hospitalization Due to COPD
Exacerbation (vs Placebo)
Tiotropium (n=550)
Placebo (n=371)
Time to first hospitalization: p=0.007*
Days on Treatment
*Log Rank Test
Twice daily
long-acting beta2 agonists
(LABA’s)
Salmeterol versus ipratropium versus placebo
in COPD: Spirometric impact Salmeterol
Change from baseline in FEV1(L)
0.5
Day 84
Ipratropium
Placebo
0.4
0.3
0.2
0.1
0.0
1
-0.1
2
3
4
5
6
7
8
9
10 11 12 13
Time (hours)
Mahler et al, 1999
Salmeterol versus ipratropium versus placebo
in COPD: Exacerbations
1.00
0.95
0.90
Probability
0.85
0.80
0.75
0.70
Salmeterol
Ipratropium
Placebo
0.65
0.60
0.55
0.50
0
1
2
3
4
5
6
7
Weeks of treatment
8
9
10
11
12
Mahler et al, 1999
Once-Daily
LABA’s
Mean Change in FEV1 on Day 1 of
Indacaterol Treatment
5 mins
post-dose
Data are unadjusted means.
Adapted from:
Novartis Pharmaceuticals Inc. Onbrez* Breezhaler* Product Monograph. Date of Revision: October 24, 2012.
Novartis Pharmaceuticals Inc. Data on file (Study B2355).
Studies Evaluating Indacaterol 75 µg:
Trough FEV1 at Week 12
Indacaterol 75 µg o.d.
*
1.55
1.49
FEV1 (L)
1.50
1.45
1.40
*
140 mL
1.38
1.35
1.35
120 mL
1.30
1.25
1.20
Placebo
1.26
n=149
n=148
Study 1
Data are least squares means ± standard errors; *p<0.001 vs. placebo
Adapted from the product monograph and data on file (studies B2354 and B2355)
n=145 n=150
Study 2
Sustained Bronchodilation Over 24
Hours: Indacaterol vs. Placebo
Improvement in FEV1 vs. placebo at every
time point, measured by 24-hour spirometry
Rapid onset within
5 minutes
Adapted from the product monograph and data on file (B2355)
Are beta2 agonists a safe choice
for a patient with COPD?
Survival (95% CI), %
Survival: LAMA versus LABA
100
95
90
85
80
75
70
65
60
55
50
45
Long-acting
β2 agonist (LABA)
Long-acting muscarinic
antagonist (LAMA)
Log-rank P < 0.001
0
1
2
Time from index date, y
3
4
5
At risk, n
LAMA
15,532
13,603
11,891
8,401
5,311
2,114
LABA
15,532
13,780
12,245
8,731
5,577
2,095
Gershon A, et al.: Ann Intern Med 2011; 154(9):583-92.
Is There a Concern About the
Cardiovascular Safety of
Inhaled Anticholinergics?
Tiotropium SMI Associated with a 52%
Increase in Mortality
Singh et al. BMJ 2011.
Tiotropium SMI 10 ug Associated
with a Doubling of Mortality
Singh et al. BMJ 2011.
Tiotropium SMI 5 ug
Number Needed to Harm
124
Singh et al. BMJ 2011.
TIOSPOR
Wise et al. Resp Res 2013
TIOSPOR – Mortality: Handihaler
vs. Respimat
Wise et al. NEJM 2013
TIOSPOR – Mortality: Handihaler
vs. Respimat
Wise et al. NEJM 2013
TIOSPOR – Exacerbation:
Handihaler vs. Respimat
Wise et al. NEJM 2013
UPLIFT - Mortality
Tiotropium
Control
n (%)
n (%)
On-Treatment
381 (12.8)
411 (13.7)
Vital Status (day 1440)
430 (14.4)
Vital Status (day 1470)
∆Rates
Hazard Ratio
Tiotropium vs. Control
HR
95% CI
P-value
0.9%
0.84
0.73, 0.97
0.016
491 (16.3)
1.9%
0.87
0.76, 0.99
0.034
446 (14.9) 495 (16.5)
1.6%
0.89
0.79, 1.02
0.086
Tashkin et al. NEJM 2008.
A Newer Once-Daily
Anticholinergic
Glycopyrronium bromide
vs. Tiotropium
M3:M2 Receptor Selectivity
Therapeutic index: similar inhibition of bronchoconstriction,
lower cardiovascular effects between glycopyrronium and
tiotropium
20 μg
•
In a rabbit model1,2
•
•
NVA237 20 μg and
tiotropium 3 μg both
inhibited methacholineinduced
bronchoconstriction
NVA237 20 μg had no
effect on the cardiovascular
response to methacholine,
in contrast to tiotropium
1. Cooper et al. Eur Resp J 2006; 2. Cooper et al. ATS 2006
Therapeutic index: similar inhibition of bronchoconstriction,
lower cardiovascular effects between glycopyrronium and
tiotropium
20 μg
•
In a rabbit model1,2
•
•
NVA237 20 μg and
tiotropium 3 μg both
inhibited methacholineinduced
bronchoconstriction
NVA237 20 μg had no
effect on the cardiovascular
response to methacholine,
in contrast to tiotropium
1. Cooper et al. Eur Resp J 2006; 2. Cooper et al. ATS 2006
Therapeutic index: similar inhibition of bronchoconstriction,
lower cardiovascular effects between glycopyrronium and
tiotropium
20 μg
•
In a rabbit model1,2
•
•
NVA237 20 μg and
tiotropium 3 μg both
inhibited methacholineinduced
bronchoconstriction
NVA237 20 μg had no
effect on the cardiovascular
response to methacholine,
in contrast to tiotropium
1. Cooper et al. Eur Resp J 2006; 2. Cooper et al. ATS 2006
Glycopyrronium bromide
vs. Tiotropium
More Rapid Onset
GLOW2: Significant improvement in FEV1 versus placebo
over 24 hours after dosing
 Improvements in FEV1 with glycopyrronium bromide were statistically superior
(compared to placebo) and clinically meaningful on Day 1* (Figure), Week 12 **
and Week 52***
Glycopyrronium bromide (n=144)
1.70
Placebo (n=79)
Tiotropium (n=76)
FEV1 (L)
1.60
1.50
1.40
1.30
1.20
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Time post dose (hours)
*All time points statistically significant (p<0.001) except 16h and 22h
**All time points statistically significant (p<0.001) except 16h, 23h15 min and 23h45 min
***All time points statistically significant (p<0.001)
Kerwin et al. ERJ 2012
Most COPD patients indicate morning as the time
when their symptoms are most severe1
Time when COPD symptoms are worse than usual
All COPD patients (N=803)
Severe COPD patients (n=289)
100
Patients (%)
60
50
40
46†
37*
34
27
30
28
25
21
20
17
16
11
10
9
9
4
7
0
Morning
•
Midday
Afternoon
Evening
Night
No particular Difficult to
time of day
say
Improvement in morning activities is a major treatment
expectation of patients2
*p<0.001 versus ‘midday’, ‘afternoon’, ‘evening’, ‘night’ and ‘difficult to say’ groups;
p=0.006 versus ‘no particular time of day’ (all COPD patients); †p<0.001 versus ‘midday’
1Partridge
1Kuychu
et al. CMRO 2009
et al. Tüberküloz ve Toraks Dergisi 2011
GLOW2: FEV1 from 5 minutes
to 4 hours post-dose on Day 1
1.8
1.7
***
1.5
1.4
†††
***
FEV1 AUC5 min–4 h
1.6
FEV1 (L)
1.6
Glycopyrronium bromide
Placebo
Tiotropium
1.5
1.4
1.3
1.2
0
1
4
2
3
Time post-dose (h)
At all time points: p<0.001 glycopyrronium bromide
vs placebo and tiotropium vs placebo
1.3
Placebo
Tiotropium
Glycopyrronium
NVA237
bromide
***p<0.001 versus placebo, †††p<0.001 versus tiotropium;
data are LSMs±SE. AUC = area under curve
Novartis, data on file
Glycopyrronium bromide 50 µg q.d.
Tiotropium 18 µg q.d.
**
Week 12
***
*
***
Week 26
*
***
IMPROVEMENT
Improvement in SGRQ total score
versus placebo (mL)
GLOW2: Improvement in SGRQ total score over placebo at
Weeks 12 (key secondary endpoint), 26 and 52
Week 52
(Glycopyrronium bromide vs placebo, key secondary endpoint)
*p<0.05, **p<0.01, ***p<0.001 versus placebo; Data are LSMs ± 95% CI
Kerwin et al. ERJ 2012
GLOW2: Exacerbation summary
Glycopyrronium bromide o.d. (N=525)
Open-label tiotropium 18 μg o.d. (N=267)
100
Patients exacerbation free (%)
Placebo (N=268)
90
80
70
60
50
40
0
4
8
12
16
20
24
28
32
36
40
44
48
52
Time to first exacerbation (weeks)
*p≤0.05; **p≤0.01; ***p=0.001
CI = confidence interval; HR = hazard ration; o.d. = once-daily; OR = odds ratio; RR = rate ratio
Kerwin et al. Eur Respir J. 2012
Aclidinium
S
O
O
HO
S
N
O
Br
 Potent M3 antagonist1 with long residence at M3 receptor1
 Long duration of action in vivo1
 Rapid hydrolysis in human plasma to two inactive metabolites2
 Low systemic exposure1
1Gavaldà
et al, J Pharmacol Exp Ther 2009; 2Sentellas et al, Eur J Pharm Sci 2010
Aclidinium is rapidly hydrolysed in human plasma
in vitro into two inactive metabolites
Remaining 120
compound
(%)
100
80
60
Aclidinium t½
2.4 minutes
40
20
0
0
12
24
36
Time (minutes)
Two major acid and alcohol metabolites are inactive
In vitro stability of aclidinium, ipratropium and tiotropium assessed in human plasma
Aclidinium
Ipratropium
Tiotropium
48
60
Gavaldà et al. ERS 2008
LAS39: Change from baseline FEV1 by timepoint
over 24 hours at Day 1
Aclidinium 400 ug
(FEV1, L)
Placebo
0.25
Tiotropium
0.2
0.15
**
0.1
**
0.05
*
0
-0.05
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
-0.1
-0.15
Evening administration
-0.2
Time after intake (h)
9:00am
Both active drugs were statistically superior to placebo
*p <0.05 aclidinium vs tiotropium
Beier et al. COPD 2013
When do we use ICS
therapy for COPD
patients?
Modest benefit for ICS in
preventing COPD exacerbations
 Use of ICS is associated with an 18% reduction in
occurrence of exacerbations
Study 1: 1.00
Study 2: 1.00
Study 3: 0.63
Rate ratio
Study 4: 0.75
Study 5: 0.66
Study 6: 0.93
Study 7: 0.66
Study 8: 0.51
Study 9: 0.82
Study 10: 1.11
Study 11: 0.91
Fixed: 0.84
Random: 0.82
0.5
ICS
1
Placebo
2
 Benefits seen primarily in patients with severe
COPD (FEV1 <50%)
Agarwal et al. Chest 2010
Is there any reason not
to use ICS therapy?
Bone Density vs. Dose and Duration of ICS
Therapy
Lumbar Spine
2.0
Ward’s Triangle
2.0
r=-0.53
p=0.01
r=-0.58
p=0.005
Z score
Z score
2.0
Femoral Neck
-2.5
-2.5
0
Dose x Duration/BMI
0
4
Dose x Duration/BMI
4
r=-0.33
p=0.08
Z score
-2.5
0
Dose x Duration/BMI
4
Hanania et al. JACI 1995.
Inhaled Corticosteroids and the Risk
of Cataracts - Dose Response
p < 0.001
Cumming et al. NEJM 1997.
Increased Risk of Pneumonia with
ICS vs. Placebo in COPD: Metaanalysis
Subgroup
# of events / # of patients
Odds Ratio
95% CI
ICS
No ICS
ICS vs. placebo
285 / 3881
180 / 3633
1.51
1.08 – 2.10
ICS + LABA vs. LABA
356 / 4754
217 / 4728
1.72
1.28 – 2.30
Total
641 / 8635
397 / 8361
1.60
1.33 – 1.92
Singh S, et al. Arch Intern Med 2009; 169(3):219-29.
Increased Risk of New-onset Diabetes
with Increasing ICS Dose
Suissa S, et al. Am J Med 2010; 123(11):1001-6.
Increased Risk of TB with ICS
Use in COPD
Hazard
Ratio
Kim et al. Chest 2013.
Increased Risk of TB with ICS
Use in COPD – North America
RR
n = 427,648 over 15 years
Brassard et al. AJRCCM 2011.
Combining
Bronchodilators in Mild
to Moderate COPD
Dual bronchodilation: proof of concept with formoterol +
tiotropium
Trough FEV1
200
*
n=108
n=118
*
Formoterol (12 µg b.i.d.)
+ tiotropium (18 µg o.d.)
n=106
*
n=121
150
n=127
n=121
n=121
100
n=129
50
0
Week 4
Week 8
Week 12
*p<0.01; †p<0.001 vs tiotropium.
Last visit
Mean change in symptom score
Change from baseline
in trough FEV1 (mL)
250
†
Total COPD Symptom Score
Tiotropium (18 µg o.d.)
0
AM
PM
AM/PM
average
-0.2
-0.4
-0.6
-0.8
-1.0
-1.2
-1.4
-1.6
*
*
*
*p<0.05 vs tiotropium.
Tashkin et al. COPD 2009
LABA/LAMA provide better improvements in lung
function at 6 weeks than LABA/ICS
Tiotropium 18 μg o.d. +
formoterol 12 μg b.i.d.
1.8
*
*
FEV1 (L)
1.7
*
*
Salmeterol 50 μg b.i.d. + fluticasone
propionate 500 μg b.i.d.
*
*
1.6
*
*
*
1.5
1.4
1.3
0
1
2
3
4
5
6
7
8
9
Time after drug administration (hours)
10
11
12
*p<0.05 between
groups
Rabe et al. Chest 2008
Once daily
combination
bronchodilators
SPARK study design
64-week, multicenter, randomized, double-blind, parallel-group and active
controlled study
Pre-randomization Period
Double-blind Treatment Period*
Variable Double-blind Treatment
Period*
QVA149 110/50μg qd via Breezhaler®
Prescreening
Screening/
Run-in
period
Glycopyrronium 50μg qd via Breezhaler®
Open-label tiotropium 18μg qd via Handihaler®
Day -21 to
Day -15
Visit 1
Day -14 to
Day -1
Visit 2
Day 1 to Week 64
Randomization Visit 3
Week 64 to
Week 76
Visit 16
Visit 18
*QVA149 and glycopyrronium both were double-blind treatments, while tiotropium was open-label; The double-blind treatment
period could be extended to a total of 76 weeks; this extension period was designed to increase the number of exacerbation
events to ensure the study achieved the exacerbation rate prespecified for analysis; Handihaler is a registered device of
Boehringer Ingelheim to deliver tiotropium
Pre-dose trough FEV1 was significantly higher with
QVA149 vs glycopyrronium and tiotropium at all
assessments
Trough FEV1(L)
1.10
Glycopyrronium
Tiotropium
1.00
0.90
0.80
0
0
4
12
26
38
52
64
Weeks
Differences between QVA149 and glycopyrronium and tiotropium were statistically significant (p<0.0001) at each assessment
during the treatment period. Data are least squares means ±SE
Pre-dose trough FEV1 was significantly higher with
QVA149 vs glycopyrronium and tiotropium at all
assessments
Trough FEV1(L)
1.10
QVA149
Glycopyrronium
Tiotropium
1.00
0.90
0.80
0
0
4
12
26
38
52
64
Weeks
Differences between QVA149 and glycopyrronium and tiotropium were statistically significant (p<0.0001) at each assessment
during the treatment period. Data are least squares means ±SE
Rate reduction of COPD exacerbations
QVA149
COPD Exacerbations (annualized rate)
5
4.5
4
3.5
Glycopyrronium
Tiotropium
0.84*
(0.75, 0.95)
0.86**
(0.78, 0.94)
0.85††
(0.77, 0.94)
0.85†
(0.75, 0.96)
3
0.90‡
(0.79, 1.02
2.5
2
0.88§
(0.77, 0.99)
1.5
1.16¶
(0.84, 1.61)
0.81||
(0.60, 1.10)
1
0.5
0
Mild exacerbations
Moderate/severe
exacerbations
Severe exacerbations
All exacerbations
Values are rate reduction (95% CI); n numbers per treatment group: QVA149 n=729; glycopyrronium n=739; tiotropium n=737.
*p=0.0052,†p=0.0072,‡p=0.096,§p=0.038,¶p=0.36,||p=0.18,**p=0.0017,††p=0.0012.
Self Management in COPD
The Health Care Utilization Impact of Education
and Self-Management in Severe COPD
Bourbeau J, et al.: Arch Intern Med 2003; 163(5):585-91.
Sample Plan
of Action
Is there a Risk to Self-Management?
Futility Analysis
for COPD
Hospitalization
p = 0.0002
Probability of
Mortality
HR: 2.68
(adjusted)
Hospital admissions and deaths due to chronic obstructive pulmonary disease, intervention
versus control group.
Bucknall C E et al. BMJ 2012;344:bmj.e1060
©2012 by British Medical Journal Publishing Group
Hospital admissions and deaths due to chronic obstructive pulmonary disease, successful vs
unsuccessful self-managers
49%
HR 0.44, p = 0.003
27%
Bucknall C E et al. BMJ 2012;344:bmj.e1060
©2012 by British Medical Journal Publishing Group
Summary
• COPD prevalence is increasing in Canada but
underdiagnosis and overdiagnosis are common
• Are anticholinergic bronchodilators preferred? No.
LABA’s probably do the job as well. But the point is
moot as we move to combination bronchodilators.
• Are anticholinergics safe in COPD? Yes, reasonably.
And they may become safer as they become more
selective.
• Are ICS overused in COPD? Yes.
Summary (cont’d)
• Are self-management plans safe or hazardous
in COPD? Both. We need to do more
homework to make sure that patients are
taught correct strategies and taught
effectively by trained educators.