A 1 Physician’s Perspective: The Impact. A 2 Clinician’s Perspective Bartolome R. Celli, MD...
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Transcript of A 1 Physician’s Perspective: The Impact. A 2 Clinician’s Perspective Bartolome R. Celli, MD...
A A 11
Physician’s Perspective:Physician’s Perspective:The Impact The Impact
A A 22
Clinician’s Clinician’s Perspective Perspective
Bartolome R. Celli, MDBartolome R. Celli, MD
Professor of MedicineProfessor of Medicine
Tufts UniversityTufts University
Boston, MABoston, MA
A A 33
COPD: Presentation OutlineCOPD: Presentation Outline
• COPD mortality and the clinicianCOPD mortality and the clinician
• Mortality can be modifiedMortality can be modified in COPDin COPD- Oxygen therapy- Oxygen therapy- Smoking cessation- Smoking cessation
- TORCH- TORCH
• Lessons from other fieldsLessons from other fields- Cardiovascular - Cardiovascular
• Useful clinical comparisonsUseful clinical comparisons
• SummarySummary
Lessons from yesterday
Lessons from today
A A 44
Age-adjusted Death RateAge-adjusted Death Rate
0
0.5
1
1.5
2
2.5
3
Proportion of 1970 rateProportion of 1970 rate
1970 2002
+103% COPD
-63% CHD-Stroke
-32% All Causes
Adapted from Jemal et al. JAMA. 2005;294:1255-1259.
A A 55
Lessons from Lessons from YesterdayYesterday
A A 661. NOTT Group. Ann Intern Med 19802. MRC Working Party. Lancet 1981
COPD Survival: Oxygen COPD Survival: Oxygen
0
20
40
60
80
100
0 12 18 24 30 36
Months
Su
rviv
al %
MRC no O2 (80)
NOTT O2 (80)
- 21%*- 21%*
* ARR
A A 771. NOTT Group. Ann Intern Med 19802. MRC Working Party. Lancet 1981
COPD Survival: Oxygen COPD Survival: Oxygen
0
20
40
60
80
100
0 12 18 24 30 36
Months
Su
rviv
al %
MRC no O2 (80)
NOTT O2 (80)
- 34%*- 34%*
* RRR
A A 88
Impact of smoking cessation Impact of smoking cessation intervention on all-cause intervention on all-cause
mortality: 14.5 year survival from mortality: 14.5 year survival from the Lung Health Study (LHS)the Lung Health Study (LHS)
Anthonisen et al. Ann Intern Med 2005
Special intervention group
Usual care group
A A 99
Impact of smoking cessation Impact of smoking cessation intervention on all-cause intervention on all-cause
mortality: 14.5 year survival from mortality: 14.5 year survival from the Lung Health Study (LHS)the Lung Health Study (LHS)
Anthonisen et al. Ann Intern Med 2005
1.00
0.95
0.90
0.85
0.80
Pro
po
rtio
n o
f p
atie
nts
wit
h n
o e
ven
t
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15Time since LHS baseline (years)
Special intervention group
Usual care group
15%*15%*
* RRR
A A 1010
New LessonsNew Lessons
TORCHTORCH
A A 1111
Primary Analysis: All-cause Primary Analysis: All-cause Mortality At 3 YearsMortality At 3 Years
Vertical bars are standard errors
0
2
4
6
8
10
12
14
16
18
0 12 24 36 48 60 72 84 96 108 120 132 144 156Time to death (weeks)
Probability of death (%)
Placebo Advair 500/50
-17.5%
NNT = 39
RR
Adapted from Calverley, et al. N Engl J Med 2007; 356: 775-789.
A A 1212
Rate of exacerbations Rate of exacerbations requiring systemic requiring systemic
corticosteroidscorticosteroids
*p < 0.001 vs placebo;†p < 0.001 vs SAL; ‡p = 0.017 vs FP
0.64*0.52*
Mean number of exacerbations/year
0.46*†‡
43% reduction0.80
0
0.2
0.4
0.6
0.8
1
1.2
Placebo SAL FP Advair 500/50
Treatment
Adapted from Calverley, et al. N Engl J Med 2007; 356: 775-789.
A A 1313
Post-bronchodilator FEVPost-bronchodilator FEV11
Adjusted mean change FEV1 (mL)
0 24 48 72 96 120 156Time (weeks)
–150
–100
–50
0
50
100
Placebo SAL FP
**
*†
Advair 500/50
1524152115341533
1248131713461375
Number ofsubjects
1128121812301281
1049112711571180
979105410781139
906101210061073
819934908975
*p < 0.001 vs placebo; †p < 0.001 vs SAL and FP Calverley, et al. N Engl J Med 2007; 356: 775-789.
A A 1414
SAL
Placebo
FP
Results - SGRQ Total ScoreResults - SGRQ Total Score
-5
-4
-3
-2
-1
0
1
2
3
0 24 48 72 96 120 156
1149114811551133
Numberof Subjects
854906942941
781844848873
726807807814
675723751773
635701686731
569634629681
Ad
just
ed
me
an C
han
ge
SG
RQ
To
tal S
core
(U
nits
)
Advair 500/50
Weeks
Vertical bars represent standard errors Calverley, et al. N Engl J Med 2007; 356: 775-789.
A A 1515
Candida & dysphoniaCandida & dysphonia
Eye EffectsEye Effects
Bone Effects Bone Effects
FEVFEV11
Quality of LifeQuality of Life
ExacerbationsExacerbations
SurvivalSurvival
Favorable Benefit / Risk Profile Favorable Benefit / Risk Profile for Advair 500/50 in COPDfor Advair 500/50 in COPD
RiskRisk Benefit Benefit
PneumoniaPneumonia
A A 1616
Lessons from Lessons from othersothers
Cardiovascular trialsCardiovascular trials
A A 1717
CHF: Beta blocker vs CHF: Beta blocker vs PlaceboPlacebo
80
90
100
0 1 2 3 4 5 6
Months
Su
rviv
al (
%)
Carvedilol
Placebo
4.6%*4.6%*
Packer et al NEJM 1996;334:1349
n = 1094n = 1094
* ARR
A A 1818
CHF: Beta blocker vs CHF: Beta blocker vs PlaceboPlacebo
80
90
100
0 1 2 3 4 5 6
Months
Su
rviv
al (
%)
Carvedilol
Placebo
65%*65%*
Packer et al NEJM 1996;334:1349
n = 1094n = 1094
* RR
A A 1919
Global Utilization of Streptokinase Global Utilization of Streptokinase and Tissue Plasminogen Activator and Tissue Plasminogen Activator for Occluded Coronary Artery trial: for Occluded Coronary Artery trial:
GUSTOGUSTO• MC, R, in 15 countriesMC, R, in 15 countries
• Four Thrombolytics in MIFour Thrombolytics in MI
• n = 41,021 n = 41,021
• F/U = 30 daysF/U = 30 days
• Deaths = 2870 (7.4%)Deaths = 2870 (7.4%)
The GUSTO Investigators. NEJM 1993
A A 2020
0
1
2
3
4
5
6
7
8
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
Days
Mo
rtal
ity
(%)
SK + H sc
SK + H iv
SK + tPA
tPA
1%*1%*
The GUSTO Investigators. NEJM 1993
* ARR
Thirty-day Mortality in the Thirty-day Mortality in the Four Treatment Groups: Four Treatment Groups:
GUSTO TrialGUSTO Trial
A A 2121
0
1
2
3
4
5
6
7
8
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
Days
Mo
rtal
ity
(%)
SK + H sc
SK + H iv
SK + tPA
tPA
10%*10%*
NNT = 100
The GUSTO Investigators. NEJM 1993
* RRR
Thirty-day Mortality in the Thirty-day Mortality in the Four Treatment Groups: Four Treatment Groups:
GUSTO TrialGUSTO Trial
A A 2222
Statins AnalysisStatins Analysis
• Studies = 5 (between 4 and 9 thousand)Studies = 5 (between 4 and 9 thousand)
• Number 30,602Number 30,602
• Mean follow up time of 5.4 yearsMean follow up time of 5.4 years
• Mean Relative Reduction in mortality by Mean Relative Reduction in mortality by 21% (0 to 31%)21% (0 to 31%)
• Mean Absolute RR = 1.6 (-0.1, 0.8, 0.9, 3.0, Mean Absolute RR = 1.6 (-0.1, 0.8, 0.9, 3.0, 3.3) 3.3)
La Rosa et al. JAMA 1999
A A 2323
Useful Clinical Useful Clinical ComparisonsComparisons
Number Needed to TreatNumber Needed to Treat
A A 2424
NNT to save 1 lifeNNT to save 1 life
tPA 100 once x 30 days
Statins 61 x 5 yrs
Advair 500/50 39 x 3 yrs
Smoking cessation 62 x 14 yrs
Beta-blocker 20 x 6 monthsBeta-blocker 20 x 6 months
Oxygen 5 x 36 monthsOxygen 5 x 36 months
0 25 50 75 100
A A 2525
Summary Summary
A A 2626
TORCHTORCH
FF
EE
VV
11
OO
LL
EE
XX
AA
CC
EE
RR
BB
AA
TT
II
OO
NN
St George’s St George’s is 3.1 better is 3.1 better
than than placebo and placebo and better than better than
baselinebaseline
92 ml 92 ml difference difference
from from placeboplacebo
25%25%reduction in reduction in
ExacerbationsExacerbations
Survival
A A 2727
The FutureThe Future
A A 2828
Age-adjusted Death RateAge-adjusted Death Rate
COPD
1970
Other causes
CHD-Stroke
2002 20202020
0
0.5
1
1.5
2
2.5
3
Proportion of1970 rate
