A Discussion of Statin Drugs in COPD and Associated Diseases to Improve Outcomes 2014
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A Discussion of Statin Drugs in COPD and Associated
Diseases to Improve Outcomes 2014
Donald M. Pell MD, FCCP
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Incidence• CDC data 7/2012• COPD is now 3rd leading cause of
death• 2008 141,075• 46.4 men@100,000• 34.2 women@100,000
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Incidence• Male mortality is down from
49@100,000• Female mortality unchanged from
2007• 75% of patients with COPD are
between 40 and 65• There are an estimated 24,000,000
US patients.• More women die annually.
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Proposed Pathophysiology of COPD
Young, Euro Resp Rev, 2009
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Pathophysiology of COPD• Cigarette smoking, inhaled aerosols,
genetic predisposition• Inflammatory process in bronchial
lumen release IL-8, sequester polys• Macrophages plus IL-8 cause poly
elastace release• Elastin is destroyed, tissue protective
protease destroyedYoung, Euro Resp Rev, 2009
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Pathophysiology of COPD• CD-8 and T lymphocytes migrate• Oxidative load crosses back into
vascular endothelium• Combines with circulating cytokines• Systemic vascular damage and
endothelial dysfunction occurs
Young, Euro Resp Rev, 2009
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Pathophysiology of COPD• Nicotine releases fibronectin causing
increased focal airway fibrosis and collagen release damaging injury repair.
• Cellular apoptosis is diminished prolonging cell life of polys and macros leading to further cell mediated injury.
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Pathophysiology• Reactive Oxidative species “spill
over” into circulation and cause systemic effects
• Muscle wasting, weakness, anemia, weight loss, osteoporosis, and premature aging of the lungs
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Relationship between COPD and Lung Cancer• 60-90% of lung cancers develop in
patients w/COPD• May share common inflammatory
pathways• Increased levels of guanine
triphosphate, growth factor and epithelial mesenchymal transition may lead to DNA changes and Cancer
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Epidemiology of COPD• Only 20-30% of people develop COPD
despite same exposure.• Genetic predisposition heavily affects
the results.• After 40 pack years, FEV1/FVC ratio
will be 70% or less and will progressively decline in this susceptible population.
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FEV1 decline defines this subset• Increased incidence compared with
smokers with normal PFT’s • Coronary artery disease• Stroke• Lung cancer
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FEV1 decline and all cause CV mortality is related • Increased levels IL6• Increased levels CRP• Increased levels TNF• Once FEV1 and FEV1/FCC decline
disease is progressive and no current approved treatment alters this course.
• Studies now focused on suppressing inflammation.
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Decreased Lung Function and the effects of statins• Normal lung aging starting at age 25
is loss 0f 18 cc FEV1/year• Burrows (NEJM 1969) showed COPD
patients loss 80 cc FEV1/year• Exacerbations increase loss 2-7cc
more/year• Progression so far not preventable
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Lung function decline and the Effect of Statins• Alexeff 803 elderly men w/o COPD
23.9 v 10.9• Keddissi in 210 w COPD 85 cc v 5 cc• Mannino in non statin users higher
decline higher mortality 171 v 62 cc loss
• Johnson 200 double lung or heart lung transplants
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Johnson Continued• One half on statins• FEV1’s at 87%=/-2 predicted v. 70%
+/-1• Slower decline over time• Episodes of grade 3 or 4 rejections
reduced from 13% to4%• Severe rejections 8% v.2%• 6 year survival 91% v. 54%
Johnson Amer Res Crit Care 2003 vol167,p1271
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Mortality Outcomes in COPDObservational Studies• Soyseth severe COPD 1.9 year study
43% less deaths in statin group• Frost 77,322 patients over 11 years
38% death reduction in all doses, 81% reduction in moderate dose.
• Mortenson 46% risk of death reduction following pneumonia hospitalization
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Mortenson, continued
Mortenson, Euro Resp Jour, 2008, vol 31, 611-17
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Proposed Pathogenesis of Lung Cancer
Young, Euro Resp Rev, 2009
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Statins Effects on Lung Cancers /All Cancers• Khurana 488,733 VAH over 6 years
found 7280 lung cancers only 1/3 on statins
• Farwell cancer risk reduction of 55% if on statins for 6 months, same as above
• Karp 30,076 7 years post MI for lung cancer admission 30% red risk on statins
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Karp continued
Karp, Am J Med vol131, p1282-8
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Karp continued• Difference in lipophilic (FLAS) group
did not induce angiogenesis• Hydrophilic (PR) group did• Did this affect earlier study
outcomes?• Death from any cancer reduced in all
3 of his groups 13.9 in high dose, 17 in low dose v. 26 in control group/100 patient yearsKarp Am J Med 2008, vol100,
p302-9
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Statins in Community Acquired Pneumonia• All showed decreased ICU transfer,
decreased death and improved outcomes
• Some studies showed COPD patients some did not
• Statins must be maintained during hospitalization
• Improved outcomes occurred also if statins were started on admission
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Conclusion• Role of inflammation is increasingly
recognized in many disease states.• Statins effects on COPD
exacerbations, outcomes in infections, and on companion diseases of Cancer, CAD and Strokes were discussed.
• While pathophysiology is further studied, better outcomes are available now.
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Pell’s Pearl• If I can just get you to think, gosh
darn it, you might amount to something. Emphasis on if, gosh darn it and might.
John B. Hickam MD Indianapolis 1968