1. Implantable Cardioverter Defibrillators to Prevent Sudden Cardiac Death: Background Frederick A. Masoudi, MD, MSPH Associate Professor of Medicine (Cardiology) University of Colorado Denver & Colorado Cardiovascular Outcomes Research Group (C-COR) AHRQ Annual Meeting, Bethesda, MD Wednesday, September 21, 2011

2. Disclosures Frederick A Masoudi, MD, MSPH: Implantable Cardioverter Defibrillators for Primary Prevention Research Grants: AHRQ, NHLBI Contracts: American College of Cardiology Foundation (Senior Medical Officer, National Cardiovascular Data Registries); Oklahoma Foundation for Medical Quality

3. Defibrillation Treats Malignant Cardiac Arrhythmias

4. Implantable Cardioverter Defibrillators (ICDs) : Preventing Sudden Cardiac Death (SCD)

5. The ICD: Revolution in Preventing Sudden Cardiac Death First ICD implantation: Johns Hopkins Hospital 2/4/1980 Implantation criteria: –>=2 cardiac arrests –Not associated with myocardial infarction –Documented ventricular fibrillation Cannom DS and Prystowsky E. PACE 2004;27:419-431. The Johns Hopkins Hospital

6. ICDs for Secondary SCD Prevention AVID Investigators. N Engl J Med 1997;337: 1576-83.

7. ICDs for Primary Prevention: Dual Evolution 1996 2010 Eligible Population for 1 o Prevention ICD

8. ICDs: Rapidly Evolving Technology http://commons.wikimedia.org/wiki/File:Edison_and_phonograph_edit2.jpg http://commons.wikimedia.org/wiki/File:Ipod-icon.svg

9. MADIT I: ICDs Prevent Death in Ischemic LVSD Moss AJ et al. N Engl J Med 1996;335:1933-40. Enrollment criteria: NYHA functional class I-III Prior myocardial infarction LVEF <0.35 Documented asymptomatic non-sustained VT Inducible, non-suppressible ventricular tachyarrhythmia on EP study (on procainamide) Results: 54% relative reduction (23% absolute reduction) in the risk of death from all causes.

10. More Studies, More Success STUDYYEARPOPULATIONOUTCOMERR/ARR MUSTT (EPS vs. no AAR) 1999 CAD LVEF <0.40 NSVT Inducible VT Death (arrhythmic) Cardiac arrest 0.24 (0.13-0.45)* ARR 19.5% MADIT-II2002 Prior MI LVEF <0.30 NYHA I-III No EPS required Death (any) 0.69 (0.51-0.93) ARR: 5.4% SCD- HeFT 2005 NYHA II-III HF LVEF <0.35 Includes non-ischemic Death (any) 0.77 (0.62-0.96) ARR: 7.2% Buxton AE et al. NEJM 1999;341:1882-1890. Moss AJ et al. NEJM 2002;346:877-83. Bardy GH et a. NEJM 2005;352:225-37.

11. Primary Prevention ICDs: Cost-Effective Sanders GD et al. NEJM 2005;353:1471-80. ICD-Associated Reduction in Death Risk (%) ICER for ICD ($ per QALY) MADIT I MUSTT MADIT IISCD-HeFT

12. ACC/AHA Guideline Recommendations for Primary Prevention ICD Therapy Jessup M et al. J Am Coll Cardiol 2009;53 Epstein AE et al. Circulation. 2008;117

13. Current Indications for ICDs “Secondary prevention” for patients who have been successfully resuscitated from SCD “Primary Prevention” for patients without a history of SCD but at high risk, including some patients with: –Severe left ventricular dysfunction (LVSD) –Long QT syndrome –Arrhythmogenic RV dysplasia –Hypertrophic cardiomyopathy

14. CMS Coverage for ICDs Expands in Response to RCTs YearCovered Indication 1999Documented familial or inherited high-risk conditions (HCM or LQTS) 2003 Prior MI >40 days prior to implantation LVEF <0.35 Inducible sustained VT/VF at EPS If LVEF 120 ms, then EPS not needed 2005 Ischemic CM, NYHA II-III, LVEF <0.35 Non-ischemic CM >9 months, NYHA II-III, LVEF <0.35 Meeting CRT criteria and NYHA IV http://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=20.4&ncd_version= 3&basket =ncd%3A20%2E4%3A3%3AImplantable+Automatic+Defibrillators

15. Theory and Practice “In theory there is no difference between theory and practice. In practice there is.” --Yogi Berra

16. Clinical Trials to the Real World Big “Voltage Loss” Older Hospitalized Patients with HF n=20,388 Subjects meeting SOLVD enrollment criteria n= 3,579 (18%) Preserved EF n=10,943 (54%) Exclusionary condition n= 523 (3%) Contraindication n=3,566 (17%) Age > 80 n= 1,777 (9%) Masoudi FA et al. Am Heart J 2003;146:250–7.

17. Theory and Practice Collide Al-Khatib SM et al. JAMA 2011;305:43-49.

18. Where are We Now? http://commons.wikimedia.org/wiki/File:Demeter_Pio-Clementino_Inv254.jpg http://commons.wikimedia.org/wiki/File:Maes_Old_Woman_Dozing.jpg

19. Expanding Knowledge of ICDs in the Real World Assessing ICD shocks: Cardiovascular Research Network (CVRN) Longitudinal Study of ICDs Comparative effectiveness in the elderly: Outcomes of ICDs in Medicare population Outcomes in Clinical Subgroups: Bayesian statistical methods with patient- level data from clinical trials