EXPEDITED REVIEW
Reduction of Morbidity and Mortality by Statins, Angiotensin-Converting Enzyme Inhibitors, and Angiotensin Receptor Blockers in Patients With Chronic Obstructive Pulmonary Disease
G.B. John Mancini, MD, FRCP(C), FACC*,*,
Mahyar Etminan, PharmD, MSc ,
Bin Zhang, MSc ,
Linda E. Levesque, BScPhm, MSc,
J. Mark FitzGerald, MD, FRCP(C) and
James M. Brophy, MD, PhD, FRCP(C), FACC
* Division of Cardiology, Vancouver Hospital, Jack Bell Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
Division of Respiratory Medicine, Vancouver Hospital, Jack Bell Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
Centre for Clinical Epidemiology and Evaluation, Vancouver Hospital, Jack Bell Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
Departments of Medicine, Epidemiology, and Biostatistics, McGill University Health Centre, McGill University, Montreal, Quebec, Canada
Manuscript received August 15, 2005;
revised manuscript received March 21, 2006,
accepted April 4, 2006.
* Reprint requests and correspondence: Dr. G. B. John Mancini, Vancouver Hospital, 3300-950 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E3. (Email: mancini{at}interchange.ubc.ca).
OBJECTIVES: The purpose of this study was to determine if statins (hydroxymethylglutaryl CoA reductase inhibitors [HMG-CoA]), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) reduce cardiovascular (CV) events and pulmonary morbidity in chronic obstructive pulmonary disease (COPD) patients.
BACKGROUND: Few current COPD therapies alter prognosis. Although statins, ACE inhibitors, and ARBs improve outcomes in CV populations, their benefits in COPD patients both with and without concomitant heart disease has not previously been studied.
METHODS: A time-matched nested case-control study of two population-based retrospective cohorts was undertaken: 1) COPD patients having undergone coronary revascularization (high CV risk cohort); and 2) COPD patients without previous myocardial infarction (MI) and newly treated with nonsteroidal anti-inflammatory drugs (low CV risk cohort). Prespecified outcomes were COPD hospitalization, MI, and total mortality.
RESULTS: These drugs reduced both CV and pulmonary outcomes, with the largest benefits occurring with the combination of statins and either ACE inhibitors or ARBs. This combination was associated with a reduction in COPD hospitalization (risk ratio [RR] 0.66, 95% confidence interval [CI] 0.51 to 0.85) and total mortality (RR 0.42, 95% CI 0.33 to 0.52) not only in the high CV risk cohort but also in the low CV risk cohort (RR 0.77, 95% CI 0.67 to 0.87, and RR 0.36, 95% CI 0.28 to 0.45, respectively). The combination also reduced MI in the high CV risk cohort (RR 0.39, 95% CI 0.31 to 0.49). Benefits were similar when steroid users were included.
CONCLUSIONS: These agents may have dual cardiopulmonary protective properties, thereby substantially altering prognosis of patients with COPD. These findings need confirmation in randomized clinical trials.
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Abbreviations and Acronyms
| | ACE = angiotensin-converting enzyme | | ARB = angiotensin receptor blocker | | CI = confidence interval | | COPD = chronic obstructive pulmonary disease | | CV = cardiovascular | | HMG-CoA = hydroxymethylglutaryl CoA reductase inhibitors | | MI = myocardial infarction | | NSAID = nonsteroidal anti-inflammatory drug | | RR = risk ratio |
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|
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|
|
|
|
|
|
|
A K Johnston, D M Mannino, G W Hagan, K J Davis, and V A Kiri
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63(7):
599 - 605.
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|
|
|
|
|
|
|
P. Albert and P. M. A. Calverley
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31(5):
1114 - 1124.
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|
|
|
|
|
|
|
W. MacNee
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Am. J. Respir. Crit. Care Med.,
April 15, 2008;
177(8):
820 - 829.
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|
|
|
|
|
|
|
M T Dransfield, S M Rowe, J E Johnson, W C Bailey, and L B Gerald
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63(4):
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|
|
|
|
|
|
|
A. Churg, M. Cosio, and J. L. Wright
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294(4):
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
M. K. Han, V. V. McLaughlin, G. J. Criner, and F. J. Martinez
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116(25):
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|
|
|
|
|
|
|
J. I. Keddissi, W. G. Younis, E. A. Chbeir, N. N. Daher, T. A. Dernaika, and G. T. Kinasewitz
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December 1, 2007;
132(6):
1764 - 1771.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Young, R. Hopkins, and T. E. Eaton
Forced expiratory volume in one second: not just a lung function test but a marker of premature death from all causes
Eur. Respir. J.,
October 1, 2007;
30(4):
616 - 622.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Agusti
Systemic Effects of Chronic Obstructive Pulmonary Disease: What We Know and What We Don't Know (but Should)
Proceedings of the ATS,
October 1, 2007;
4(7):
522 - 525.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Tino, L. B. Ware, and M. Moss
Clinical Year in Review IV: Chronic Obstructive Pulmonary Disease, Nonpulmonary Critical Care, Diagnostic Imaging, and Mycobacterial Disease
Proceedings of the ATS,
September 15, 2007;
4(6):
494 - 498.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. B. J. Mancini
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Chest,
April 1, 2007;
131(4):
950 - 951.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. J. Frost, H. Petersen, K. Tollestrup, and B. Skipper
Influenza and COPD Mortality Protection as Pleiotropic, Dose-Dependent Effects of Statins
Chest,
April 1, 2007;
131(4):
1006 - 1012.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Soyseth, P. H. Brekke, P. Smith, and T. Omland
Statin use is associated with reduced mortality in COPD
Eur. Respir. J.,
February 1, 2007;
29(2):
279 - 283.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. H. Le Jemtel, M. Padeletti, and S. Jelic
Diagnostic and Therapeutic Challenges in Patients With Coexistent Chronic Obstructive Pulmonary Disease and Chronic Heart Failure
J. Am. Coll. Cardiol.,
January 16, 2007;
49(2):
171 - 180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Ceconi and R. Ferrari
One heart, two lungs together forever.
Am. J. Respir. Crit. Care Med.,
November 1, 2006;
174(9):
962 - 963.
[Full Text]
[PDF]
|
|
|
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