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

Study partners Phoenix Fire Department Jennifer Devine, BSN, RN, RVT 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

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.

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

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.

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

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)

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)

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

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

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

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

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

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

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

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)

Questions?

Entry criteria Inclusion Exclusion 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