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 FEV1 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 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

Methods Cont’d

Inclusion Criteria Exclusion Criteria

40-80 years of age Active 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

FEV1/FVC < 70% post bronchodilator use

FEV1 < 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

Results- Primary & Secondary Outcomes

Outcome Simvastatin

Placebo P-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

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. 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.