Firefighter Statin Trial: Reducing Atherosclerotic Disease and Risk Factors (EMW-2009-FP-00343)

1. Firefighter Statin Trial:Reducing Atherosclerotic Disease and Risk Factors (EMW-2009-FP-00343) Presenter Jeff Burgess, MD, MS, MPH University of Arizona AFG R&D Meeting Denver, CO August 23, 2013

2. Study partners • Phoenix Fire Department Dr. Timothy England, Sharon Bollinger RN, Dr. Howard Wernick, Dr. John Dominguez, Dr. Steven Reinhart, Patrick Kelley PAC, Forrest Gorter PAC, Joseph Houk PAC, Dave Larson PAC • Jennifer Devine, BSN, RN, RVT • Sally Littau, MT (ASCP) • Dr. Matthew Allison, UCSD • Dr. Richard Gerkin, Banner Health

3. Background • Increasing IMT is associated with a higher risk of cardiac events • Firefighters with LDL-C >100 mg/dl have increased IMT (Burgess et al., 2012)* • Statin therapy has been shown to reduce IMT progression and future cardiac events • Firefighters with LDL-C <160 mg/dl rarely receive statin therapy *Burgess JL, Kurzius-Spencer M, Gerkin R, Fleming J, Peate W, Alison M. Risk factors for subclinical atherosclerosis in firefighters. JOEM 2012;54:328-335.

4. Study aims • Evaluate if rosuvastatin over a 24 month period prevents progression of carotid intima-media thickness (IMT) • Measure the effect of rosuvastatin on TC, LDL-C, HDL-C, triglycerides and other biomarkers of cardiovascular risk • Determine if changes in lipids and other biomarkers of cardiovascular risk are associated with change in carotid IMT

5. Methods • Firefighters (n = 124) with fasting LDL-C 100-159 mg/dl and not currently taking statins randomly assigned to rosuvastatin 10 mg daily or control group. • Baseline, 12 and 24 month IMT measurements of the CCA, carotid bifurcation and ICA as well as lipids and other cardiovascular biomarkers.

6. Preliminary 24 month results • Enrollment 10/15/2010 - 6/17/2011 • 120/124 firefighters completed two years • 42 (68%) of 62 statin subjects remained in the treatment group • 37 took the medication daily • 3 took it 5-6 days a week • 1 took it 4-5 days a week • 1 did not answer the question • 75/120 CIMT yr 2 scans analyzed to date

7. Assignment group changes • Statin group changes (20) • Skeletal muscle effects (9) • Nausea, pain in upper stomach (2) • Joint pain (3) • Tiredness, Weakness (1) • Memory Loss, Altered mental status (2) • Noncompliance (2) and left fire service (1) • Control subject changes (6) • Left fire service or unable to schedule (3) • Started on statin therapy (3)

8. FDA notice 2/2012 • Reversible memory loss and confusion, uncommon and generally in individuals >50 years of age • 2 individuals stopped statin therapy • Increased glucose levels / diabetes risk • 1 participant stopped statin therapy (glucose levels were normal)

9. -40.0 mg/dl p<0.01 -49.0 mg/dl p<0.01

10. -38.0 mg/dl p<0.01 -48.0 mg/dl p<0.01

11. 2.0 mg/dl P=0.20 5.0 mg/dl p<0.01

12. -25.0 mg/dl p<0.01 -25.7 mg/dl p<0.01

14. -0.022 mm p=0.25 -0.005 mm p=0.77

15. -0.011 mm p=0.61 -0.032 mm p=0.11

16. Other • Ultrasound incidental findings • 8 thyroid cysts or nodules (5 control / 3 statin) • 1 identified during enrollment ultrasound • 5 new thyroid findings identified at 12 month • 2 new thyroid findings identified at 24 month • 1 thyroid nodule (statin) - removed • 1 lymph node mass (control) – removed

17. Preliminary summary • Beneficial incidental CIMT findings • Statin treatment drop-out rate (32%) greater than anticipated • Statin treatment resulted in marked decreases in TC and LDL-C • Fasting glucose not significantly increased • 2nd year CIMT and additional biomarker analysis in progress • Cost effectiveness? (>$1,825 annually/FF)

18. Questions?

19. Entry criteria • Inclusion • LDL-C = 100-159 mg/dl • Active duty, no plans to leave/retire for 2 yr • Not currently on or a candidate for statin Rx • Exclusion • Female firefighter of child bearing age • Use of certain prescribed drugs • Use of niacin/red yeast rice • Known liver disease or abnormal LFTs • Renal insufficiency/hypothyroidism