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

History

 “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

Quick Recap

STATCOPE Trial Methods  Multi-center randomized, parallel-group, placebo controlled trial (March 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

Methods Cont’d Inclusion CriteriaExclusion Criteria 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

Results

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

Results- Acute Exacerbations per per-yr

Results- Effect of Statin on time to first exacerbation

Results

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.

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

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

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

References  Criner GJ et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med Jun 5;370(23): doi: /NEJMoa Epub 2014 May 18.  Jain, Mukesh K et al. Anti-Inflammatory Effects of Statins: Clinical Evidence and Basic Mechanisms. Nature Reviews Drug Discovery 4, 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 Dec;132(6): Epub 2007 Oct 1.