Patient Selection for Primary Prevention Implantable Cardioverter Defibrillators in the

Cardiovascular Research Network: A Comparison with a National Study

Robert Greenlee, PhD, MPHMarshfield Clinic Research Foundation

Univ. of Wisconsin Institute for Clinical and Translational Research Graduate Program in Clinical Investigation

Abstract Co-authors

• David Smith – KPNW• Jane Saczynski, Jerry Gurwitz – Meyers• Kristi Reynolds – KPSC• David Magid, Liza Reifler, Nat Jackson, Karen Glenn

– KPCO• Alan Go – KPNC• Andrea Cassidy-Bushrow – HFHS• Humberto Vidaillet – Marshfield • Frederick Masoudi – UC-Denver/KPCO

Presentation Overview

• Background– Implantable Cardioverter Defibrillators (ICDs)

– Translation/Effectiveness Issues

• CVRN Longitudinal Study of ICDs– Design, Data Sources

– Aim 1 Methods

– Preliminary Results

• Implications/Next Steps• Acknowledgments

Implantable Cardioverter Defibrillators (ICDs) to Prevent

Sudden Cardiac Death (SCD)

www.bostonscientific.com

Indications for ICDs

• Demonstrated Reductions in Risk of SCD by RCTs

– Secondary prevention for patients who have been successfully resuscitated from SCD or have unstable ventricular tachycardia (VT) not due to a reversible cause

– Primary Prevention for patients without a history of SCD/unstable VT but at high risk, including some patients with:

– Severe left ventricular systolic dysfunction (LVSD)

– Long QT syndrome, Arrhythmogenic RV dysplasia, Hypertrophic cardiomyopathy

• ICD implantation also has high costs, risk of complications, and potential negative influences on quality of life

From Trial-Based Efficacy to Effectiveness in Community Care

• What about patients at the margins of key clinical indication eligibility criteria from RCTs?– CMS mandated data collection (NCDR ICD Registry)

– Practice Guidelines: “Best to have ICDs offered to patients with clinical profiles as similar to those included in the trials as possible” [Epstein et al., Circ 2008;117:e350-3408]

• How well do devices work in patients that do not otherwise look like trial participants? – Age, gender, comorbidity differences in community care ICD

patients [Masoudi et al., Circ QCO 2012; in revision]

• Utilization/Disparities, e.g., Who should be getting a device but is not? Who is getting a device but perhaps should not be?

‘Non-Evidence-Based’ ICD Implantations• NCDR ICD registry based study [Al Khatib et al., JAMA

2011;305(1):43-49]

– 22.5% of primary prevention implants were ‘non-evidence-based’

• higher risk of in-hospital mortality/post-procedural complications

• substantial hospital variation (0-60%)

• Not reducing over time

• Provocative and controversial issue– Arguments: Data limitations, criteria interpretations,

clinical appropriateness, semantics, etc.

• Department of Justice audits [Steinberg and Mittal, JACC 2012;59:1270-1274]

CVRN Longitudinal Study of ICDs:Design

• Seven (7) participating CVRN sites– Kaiser Permanente (Colorado, Northern California, Southern

California, Northwest), Marshfield Clinic, Henry Ford, Meyers/Fallon

– 14 implanting facilities (range per site 1-5)

• Observational cohort (n=2639) – 3 years post implant follow-up for clinical/device therapy outcomes

• Subject Eligibility– First ICD implant 2006-2009

– Primary Prevention

– Systolic dysfunction: Ejection Fraction <50%

– Follow-up care in participating site health care systems

CVRN Longitudinal Study of ICDs:3 Data Sources

• NCDR ICD Registry

• CVRN - Virtual Data Warehouse

• Novel repository of treated arrhythmic episodes Treated episodes

(shocks, ATPs)

Analysis Methods• Aim 1: Identify the extent to which patients with LVSD

receiving ICDs for primary prevention of SCD meet guideline-recommended implantation criteria.

• Used criteria from national NCDR-based study*– Includes:

• First time primary prevention implants

• Cardiomyopathy of ischemic or non ischemic etiology

• Past MI with ejection fraction <=30%; or CHF with ejection fraction <=35%

• Adult

– Excludes:

• history of sustained ventricular tachyarrhythmia

• cardiac resynchronization therapy devices

*Al Khatib et al., JAMA 2011;305(1):43-49

Analysis Methods• Outcome as defined in same national study*:

– ‘Non-Evidence-based’; Any one of the following:

• MI within 40 days before ICD implantation

• CABG within 3 months before ICD implantation

• Advanced heart failure symptoms (NYHA IV)

• Newly diagnosed heart failure (within 3mos)– Described as a proxy: Practice Guidelines require low EF

despite optimal medical therapy; Al Khatib assumed this can not be established in recently diagnosed CHF cases.*

– Approximates CMS coverage eligibility exclusions

*Al Khatib et al., JAMA 2011;305(1):43-49

Aim 1 Preliminary ResultsOverall

• 1726 of 2639 subjects in cohort (65%) met the inclusion criteria for analysis.

• 301 of 1726 (17%) had one or more of the criteria defining non-eligible implants

Aim 1 Preliminary Results:Individual Criteria

• Previous MI– No 745 (43.2%)– Yes > 40 days 835 (48.4%)– Yes <= 40 days 145 ( 8.4%)

• CHF Duration– None 214 (12.4%)– Yes > 3 mos 1352 (78.3%)– Yes <=3 mos 160 ( 9.3%)

• NYHA Class– I 236 (13.7%)– II,III 1465 (84.9%)– IV 22 ( 1.3%)

Aim 1 Preliminary Results:Demographic Differences

Variable Value Implant Criteria Met

Implant Criteria Not Met

P-Value

Implant Age

Mean 65.4 67.2 0.0124

Std. dev. 11.8 11.1

Sex

Male 1091 (81%) 254 (19%) 0.0087

Female 328 (88%) 47 (12%)

Race

White 916 (83%) 190 (17%) 0.7462

Non-white 500 (82%) 110 (18%)

Summary of Preliminary Findings

• About 1 in 6 primary prevention ICD patients in the CVRN LSICD fall outside of ICD eligibility criteria using published definitions from a national NCDR study.– Driven more by recent MI/CHF diagnoses than severe

CHF symptoms or recent CABG (0.3% of total)– More common among men than among women– Non-eligible slightly older– No difference by race– Somewhat lower in the CVRN LSICD than in NCDR as a

whole

Implications• Caution in interpretation

– Outcome measure definitions based on one used in national data analysis; legitimate debate about what that represents; e.g.,

• Outside of eligibility criteria if MI within 40 days, but what if also one > than 40 days - 65/145 (45%) in our data

• Less evidence for excluding recent onset CHF patients

• Definitely some overutilization occurring• Can not evaluate underutilization - Only studying

implant recipients, not the full population of those at risk

• Further study encouraged

Next Steps for Aim 1 Analyses

• finalize ‘non-eligible’ outcome; incorporate current best thinking on meaning of the criteria

• descriptive analysis to look for additional non-demographic correlates of ‘non-eligible’ implants

• Use ‘non-eligible’ implant as cofactor/ stratification in future analyses of other outcomes

– Clinical (complications, hospitalization, mortality, cost)

– Rates of appropriate and inappropriate therapy

CVRN Longitudinal Study of ICDs: FundingThis project was funded under Contract No. 290-05-0033

from the Agency for Healthcare Research and Quality, US

Department of Health and Human Services as part of the

Developing Evidence to Inform Decisions about

Effectiveness (DEcIDE) program; and by the American

College of Cardiology Foundation; with support from the

National Heart, Lung, and Blood Institute. While the

sponsoring organizations have been involved in discussions

of this research as it has progressed and have provided

oversight and guidance, the authors of this report are solely

responsible for its content. Sponsorship may not be

construed as an endorsement of all statements in the report

by the Agency for Healthcare Research and Quality, the

National Heart, Lung, and Blood Institute, the US

Department of Health and Human Services, or the American

College of Cardiology Foundation. Acknowledgments: The

authors appreciate the efforts of study team members at all

participating sites, as well as the support from funder and

stakeholder organizations.

CVRN Longitudinal Study of ICDs: Investigative Team• KPCO: Frederick Masoudi MD (co-PI), David Magid MD, Karen Glenn BS,

Nathaniel Jackson MS, Laura Muhs, Heather Nuanes, Pamela Peterson MD, Liza Reifler MPH, Paul Varosy MD

• KPNC: Alan Go MD, Jason J. Dea, Dongjie Fan, MSPH, Michael Lauer, MD PhD, Liliana V. Metzger, Nina Sasso, Kiranjit Sidhu, Ashley Spooner, Sue Hee Sung, MPH

• KPNW: David Smith RPh, PhD, Jill Mesa, Amanda Petrik, Carmel Wax• KPSC: Kristi Reynolds PhD MPH, Britta Amundsen, MA, Jonathan Doris MD, Nigel

Gupta, MD, Teresa Harrison MS, Jacqueline Porcel, MPH, Tony Yiu, MS• Marshfield Clinic Research Foundation/ Marshfield Clinic: Robert Greenlee

PhD, MPH (co-PI), Marilyn Bruger, Jay Fuehrer, Romel Garcia-Montilla MD, John Hayes, MD, Aaron Miller PhD, Deborah Multerer, Param Sharma MD, Mary Suits RN, Jeff Van Wormer PhD, Humberto Vidaillet MD

• Meyers Fallon: Jerry Gurwitz, MD, Robert J. Goldberg, PhD, Jane S. Saczynski, PhD, Jackie Fuller, Mark Mooradian, Christopher Malone, Joann (Baril) Wagner

• Henry Ford Health System: Andrea Cassidy-Bushrow PhD, Claudio Schuger MD, Dayna Johnson, MPH, Richard Krajenta, BS, Michelle Brown, RN, Debra Veryser, BA, RHIT, Judith Lehman RN, Claire Hooker, Heather Dakki MPH

• Mayo Clinic: Stephen Hammill, MD• Touro College: Alan Kadish, MD

CVRN Longitudinal Study of ICDs

• Additional Acknowledgments– ACC and NCDR Staff– Harvard Pilgrim DEcIDE staff

• Disclosures of Authors– Dr. Masoudi has a contract with the American College of Cardiology

Foundation.– Dr. Vidaillet’s contribution was supported in part by grant

1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health.