Implantable Cardioverter Defibrillators to Prevent Sudden Cardiac Death:

Background

Frederick A. Masoudi, MD, MSPHAssociate Professor of Medicine (Cardiology)

University of Colorado Denver & Colorado Cardiovascular Outcomes Research Group (C-COR)

AHRQ Annual Meeting, Bethesda, MDWednesday, September 21, 2011

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

Defibrillation Treats Malignant Cardiac Arrhythmias

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

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

fibrillationCannom DS and Prystowsky E. PACE 2004;27:419-431.

The Johns Hopkins Hospital

ICDs for Secondary SCD Prevention

AVID Investigators. N Engl J Med 1997;337: 1576-83.

ICDs for Primary Prevention: Dual Evolution

1996 2010

Eligible Population for 1o Prevention ICD

ICDs: Rapidly Evolving Technology

http://commons.wikimedia.org/wiki/File:Edison_and_phonograph_edit2.jpghttp://commons.wikimedia.org/wiki/File:Ipod-icon.svg

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.

More Studies, More Success

STUDY YEAR POPULATION OUTCOME RR/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-II 2002

•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.

Primary Prevention ICDs:Cost-Effective

Sanders GD et al. NEJM 2005;353:1471-80.

ICD-Associated Reduction in Death Risk (%)

ICER

for

ICD

($ p

er

QA

LY)

MADIT IMUSTT

MADIT IISCD-HeFT

ACC/AHA Guideline Recommendations for Primary Prevention ICD Therapy

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Jessup M et al. J Am Coll Cardiol 2009;53Epstein AE et al. Circulation. 2008;117

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

CMS Coverage for ICDs Expands in Response to RCTs

Year Covered Indication

1999 Documented 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 <0.30 and QRS>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

Theory and Practice

“In theory there is no difference between theory and practice. In practice there is.”

--Yogi Berra

Clinical Trials to the Real WorldBig “Voltage Loss”

Older HospitalizedPatients with HF

n=20,388

Subjects meeting SOLVD enrollment criteria

n= 3,579 (18%)

Preserved EFn=10,943 (54%)

Exclusionary condition

n= 523 (3%)

Contraindicationn=3,566 (17%)

Age > 80n= 1,777 (9%)

Masoudi FA et al. Am Heart J 2003;146:250–7.

Theory and Practice Collide

Al-Khatib SM et al. JAMA 2011;305:43-49.

Where are We Now?

http://commons.wikimedia.org/wiki/File:Demeter_Pio-Clementino_Inv254.jpghttp://commons.wikimedia.org/wiki/File:Maes_Old_Woman_Dozing.jpg

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