A Discussion of Statin Drugs in
COPD and Associated Diseases to
Improve Outcomes 2014
Donald M. Pell MD, FCCP
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
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.
Proposed Pathophysiology of
COPD
Young, Euro Resp Rev, 2009
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 destroyed
Young, Euro Resp Rev, 2009
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
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.
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
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
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.
FEV1 decline defines this subset
• Increased incidence compared with
smokers with normal PFT’s
• Coronary artery disease
• Stroke
• Lung cancer
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.
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
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
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
Mortality Outcomes in COPD
Observational 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
Mortenson, continued
Mortenson, Euro Resp Jour, 2008,
vol 31, 611-17
Proposed Pathogenesis of Lung
Cancer
Young, Euro Resp Rev, 2009
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
Karp continued
Karp, Am J Med vol131, p1282-8
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
years
Karp Am J Med 2008, vol100,
p302-9
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
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.
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