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 destroyedYoung, 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 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
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 yearsKarp 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