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A Discussion of Statin Drugs in COPD and Associated Diseases to Improve Outcomes 2014

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 3 rd 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

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A Discussion of Statin Drugs in COPD and Associated Diseases to Improve Outcomes 2014

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  1. A Discussion of Statin Drugs in COPD and Associated Diseases to Improve Outcomes 2014 Donald M. Pell MD, FCCP

  2. 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

  3. 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.

  4. Proposed Pathophysiology of COPD Young, Euro Resp Rev, 2009

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. FEV1 decline defines this subset • Increased incidence compared with smokers with normal PFT’s • Coronary artery disease • Stroke • Lung cancer

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. Mortenson, continued Mortenson, Euro Resp Jour, 2008, vol 31, 611-17

  18. Proposed Pathogenesis of Lung Cancer Young, Euro Resp Rev, 2009

  19. 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

  20. Karp continued Karp, Am J Med vol131, p1282-8

  21. 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

  22. 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

  23. 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.

  24. 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

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