1. Criner et al. NEJM 2014: 370; 23 Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE) Presented by Ali Naqvi, MD

2. History

3.  “Use of Statins and Lung Function in Current or Former Smokers” – Keddissi, et al.  Retrospective Cohort study at Okalahoma City’s VA Hospital in 2005  Conducted chart reviews of 418 patients: Statin vs. Non-statin  Smokers or Former-smokers  Abnormal baseline PFT findings (2x’s 6 months apart), with either obstructive (n= 319) or restrictive disease (n = 99)  End points to evaluate decline in PFT’s & need for urgent care  Results: Statin group had lower decline in FEV 1 and FVC vs. non-statin group (p<0.001)& ↓ urgent care visits in obstructive patients (p<.02)  Conclusion: Statins can be an effective tx for lung disease

4. Quick Recap

5. STATCOPE Trial Methods  Multi-center randomized, parallel-group, placebo controlled trial (March 2010- Oct 2013)  Primary Exposure: 40mg Simvastatin vs. Placebo  Primary Outcome:  Exacerbation Rate (# of exacerbations per person-year)  Secondary Outcomes:  Time to First Exacerbation  Severity of Exacerbation (mild, moderate, severe, very severe)  Quality of Life (SGRQ & SF-36 questionnaires)  Spirometric Values

6. Methods Cont’d Inclusion CriteriaExclusion Criteria 40-80 years of ageActive Liver Disease or alcoholism Clinical Diagnosis of Moderate-to-Severe COPD based on GOLD criteria History of statin use or require statin based on ATP III guidelines FEV 1 /FVC < 70% post bronchodilator use FEV 1 < 80% post bronchodilator use Receiving medications contraindicated with statins 10+ pack year smoking history In the past year (need one of the following): -Use of oxygen -Use of steroids or antibiotic agents for respiratory issues -ED presentation or admission for COPD

7. Results

9. Results- Primary & Secondary Outcomes OutcomeSimvastatinPlaceboP-value FVC, % pred-0.83 (-7.19, 5.28) -0.93 (-7.16, 5.4) 0.6832 FEV1, % pred-0.86 (-11.04, 8.67) -1.81 (-10.62, 7.10).1461 FEV1/FVC-0.21 (-6.91, 5.47) -0.21 (-5.04, 5.98).3581

10. Results- Acute Exacerbations per per-yr

11. Results- Effect of Statin on time to first exacerbation

12. Results

13. Interim Analysis/Monitoring Plan  Data & Safety monitoring board conducted interim analysis every 6 months during the study  After 3 years, when all primary and secondary outcome measures were the same between the two groups, the data and safety monitoring board voted to stop the STATCOPE trial due to futility.

14. Conclusions  Simvastatin 40mg did not affect exacerbation rates for patients with moderate-to-severe COPD  Simvastatin also had no effect on lung function or disease- specific quality of life  Simvastatin has no role in the prevention of exacerbations in patients with moderate-to-severe COPD

15. Author reported limitations  Limitations  Terminated study after 3 years due to futility  Lack of use of an inflammatory marker (CRP or ESR) to screen patients for enrollment in the study  Limited to those only with moderate-to-severe COPD

16. Critical Appraisal (Strengths/Weaknesses)  Strengths  Study design  Excellent Follow-Up rates  Sample size  Weaknesses  No information provided regarding blinding of investigators (may introduce bias)  Self-reported exacerbation events and adherence by subjects

17. References  Criner GJ et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med. 2014 Jun 5;370(23):2201-10. doi: 10.1056/NEJMoa1403086. Epub 2014 May 18.  Jain, Mukesh K et al. Anti-Inflammatory Effects of Statins: Clinical Evidence and Basic Mechanisms. Nature Reviews Drug Discovery 4, 977-987 2005 December.  Keddissi JI, Younis WG, Chbeir EA, Daher NN, Dernaika TA, Kinasewitz GT. The use of statins and lung function in current and former smokers. Chest. 2007 Dec;132(6):1764-71. Epub 2007 Oct 1.