Real World Effectiveness of Implantable Cardioverter Defibrillators in Medicare Patients

1. Real World Effectiveness of Implantable Cardioverter Defibrillators in Medicare Patients SokoSetoguchi, MD, DrPH Duke Clinical Research Institute, Durham, NC Project Contract Site Brigham and Women Hospital, Boston, MA 1

2. Disclosure • Conflicts of interest: None • Sources of funding: Contract No.HHSA290-2005-0016-I –TO8 from the AHRQ as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program and Contract 500-2010-00001I TO6 and Contract 500-2010-00001I TO2 from the CMS. • Dr. Setoguchi is supported by a mid-career development award grant K02-HS017731 from AHRQ. • The presenter is responsible for the content. Statements in the presentation should not be construed as endorsement by the AHRQ, CMS or the US Department of Health and Human Services. 2

3. Ongoing DEcIDE Task Order • Title: Analysis of Data Associated with CMS Coverage with Evidence Development Initiatives • Real World Effectiveness of Carotid Artery Stenting and Implantable Cardioverter Defibrillators in Medicare Patients • Fund: interagency contract between AHRQ and CMS • Contract site: Brigham and Women’s Hospital DEcIDE Center 3

4. Outline • Introduction and current status of our CMS ICD project • Presentation of results from a recently completed ICD study

5. Implantable Cardioverter Defibrillators (ICDs) 5

6. ICDs in Real World Real world patients receiving ICDs Median age: 74 yrs Non-cardiac comorbidities are common 36% Diabetes 22% Chronic lung disease Insurance Type 77% CMS American College of Cardiology National Cardiovascular Data Registry (ACC NCDR) Report Benefit of ICD is not established in: elderly patients those with comorbidities real world practice setting 6

7. ICD Study: Aims • Aim 1: To demonstrate differences in the incidence rate of death and cardiovascular hospitalizations between trial populations and Medicare patients undergoing ICD implantation. • Aim 2: To explore the incidence of death and cardiovascular hospitalizations in subgroups of patients undergoing ICD implantation by gender, age category, and comorbidities. • Aim 3: To identify subgroups of patients undergoing ICD implantation for whom 1) ICDs are not effective (expected survival < 18 months) and 2) ICDs are not cost-effective (expected survival < 5 years). • Aim 4: To estimate the incidence of various potential short and long-term adverse events following ICD implantation. • Aim 5: a) To directly compare ICD vs. medical management and b) to assess the impact of unmeasured confounding in a well-designed comparative effectiveness study. 7

8. Key Features of the DEcIDE CMS ICD Study 8

9. Bringing In Multiple Players 9

10. BWH DEcIDE Center Core Team Soko Setoguchi Iwata, MD DrPH (PI, BWH/Duke) John Seeger, PharmD, DrPH (Site PI) Natasha (Chih-Ying ) Chen, PhD (Research Fellow) Lauren Williams, BA (Research Assistant) Helen Mogun, MS and Jun Liu, MD MPH (Programmers) Clinical Experts Lynne Warner Stevenson, MD (Co-Investigator) Garrick Stewart, MD, MPH (Co-Investigator) Method Experts Sebastian Schneeweiss, MD ScD (BWH DEcIDE PI) Robert Glynn, PhD ScD (Co-investigator) Core Investigator Team 10 *Deceased

11. Contracting/Supporting Groups/Individuals • Outcome Sciences Inc. • Providing the national clinical registries for HF and myocardial infarction (MI) • Nancy Dreyer, PhD • ACC NCDR • Supplementing CMS ICD Registry with data from ACC NCDR ICD Registry • Center for Outcomes Research and Evaluation (CORE), Yale-New Haven Hospital • Bridging BWH DEcIDE Center and ACC NCDR • Collaborating on the ICD complication aim • Brown University • Melissa Clark, PhD, Brown University for the supplemental survey study • Univ. of British Columbia • Winson Cheung, MD MSc for the supplemental survey study 11

12. TEP members • Jeptha Curtis, MD (Yale School of Medicine & Yale-New Haven Hospital, New Haven, CT) • Sherri Dodd, MS (Medtronic Inc, Minneapolis, MN) • Kenneth Ellenbogen, MD (Virginia Commonwealth University Pauley Heart Center, Richmond, VA) • Marcel E. Salive, MD, MPH (National Institute on Aging at National Institutes of Health, Bethesda, MD) • Lynett Voshage Stahl (Boston Scientific Corporation, Arden Hills, MN)

13. Putting Multiple Data Sources Together 13

14. 2) A portion of the NCDR ICD registry including identifiers, reason for admission, prior heart failure hospitalization, QRS duration, Creatinine, B-type natriuretic peptide, and systolic blood pressure HF/MI registry Medicare Files Medicare Files Medicare Files Medicare Files HF/MI registry Linkage Information (STAGE 2) Linkage Information (STAGE 2) Outcome ID#CMS ID# ACC- NCDR registry ACC- NCDR registry CMS ICD registry CMS ICD registry Brigham DEcIDE Center 3) CMS ICD registry with identifiers 4) ACC-NCDR variables added to CMS ICD registry 5) CMS sends Medicare files (100% Denominator & MedPAR) to BWH DEcIDE Center 6) BWH DEcIDE Center receives Medicare Files (STAGE 1) 7) Partial linkage information: SSN 8) CMS receives partial linkage information (STAGE 2) 1) Dataset of entire study cohort (65+) and linkage information* 10) BWH DEcIDE Center receives Medicare Files (STAGE 2) Research Database 9) Extract Medicare Part A, B, and D files using partial linkage information *HF/MI Registry: Clinical Registry from Outcome DEcIDE Center for heart failure and myocardial infarction 11) Creation of Research Database using Medicare files and linkage information 14

15. Multiple Studies are Underway to Inform….. • Long-term outcomes (benefit and complications) after ICD implantation • Who benefit or don’t benefit from ICDs • Methodological challenges and potential solutions in assessing effectiveness of ICDs using large databases • Clinical effectiveness of ICDs and magnitude of potential bias in observational studies ……..in Medicare patients

16. Survival after ICD Implantation in Medicare Patients with Heavy Burden of Heart Failure Natasha Chen, Lynne Warner Stevenson, John D Seeger, Lauren Williams, Jessica J Jalbert, Andrew Rothman, Garrick C Stewart, Soko Setoguchi

17. Background and Purposes • Little is known about long-term survival after primary ICD implantation in Medicare patients • especially in those with heavy burden of HF and other comorbidities • To describe survival following primary ICD implantation and assess the impact of the burden of HF on survival

18. Data Sources • Centers for Medicare & Medicaid Services ICD registry • Medicare Provider Analysis and Review (MedPAR) • Years 2005 - 2008 • Linked by a previously described method using multiple non-unique identifiers • Date of birth, date of admission, gender, hospital ID

19. Study Design Recipients in CMS-ICD registry+ MedPAR files (Year 2005-2008) Recipients met indications for primary ICD -EF ≤ 35% -No cardiac arrest/sustained VT Recipients of prophylactic ICD - ≥ 1yr eligibility - Age ≥ 66 yrs Outcomes All-cause mortality Censoring ICD removal Loss of eligibility 12/31/2008 Index time 1st ICD implantation

20. HF Burden and Analysis • Chronic burden of HF • Number of HF hospitalizations in the previous year • Acute burden of HF • Days from admission to implant during HF/ICD hospitalization • Kaplan-Meier survival estimates for crude mortality • Cox proportional hazard regression models for adjusted hazard ratios (HRs).

21. Table 1 Main characteristic and outcomes among Medicare beneficiaries receiving prophylactic ICD implantations Characteristics for Medicare ICD patients (N=66,974)

22. Outcomes in Overall Medicare Primary ICD Patients (N=66,974)

23. Mortality after ICD Implant (N=66,974) 3 Year Mortality Medicare ICD Patients 31% SCD HeFT 16% MADIT II 22%

24. Characteristics by Number of Hospitalizations

25. Mortality by # of HF Hospitalizations in the Past Year

26. Risk of Mortality in Patients with >=1 HF Hospitalizations During 1 Year Prior to Implant vs. Those with No Prior Hospitalizations in the Past Year

27. Characteristics by Number of Days from Admission to Implantation

28. Mortality by # Days from Admission to Procedure

29. Risk of Mortality in Patients with >=1 Days Prior to Implant vs. Those with Implant on Admission Day

30. Conclusion • In 3 years, nearly one third of patients receiving a primary ICD implantation were died in this Medicare population • 3-year Mortality increased to 1/2 among patients with at least 2 HF hospitalizations or 7 days between admission and implantation

31. Implications • Indications and potential benefits should be carefully weighed when considering primary ICD implantation for Medicare patients with greater HF burden

32. Acknowledgement Agency for Healthcare Research and Quality • Elise Berliner, PhD Centers for Medicare and Medicaid • Rosemarie Hakim, PhD 32

34. 216,884 ICD implantations in those aged >= 65 yrs between 2005 and 2008 Excluded 26,106 (12%) records with incomplete information on linkage variables: admission dates, provider ID, date of birth, and gender 190,778 records with complete linkage variables Excluded 4,032 with missing EF 4,498 with EF > 35% 24,227 with repeated ICD 27,810 for secondary prevention 14,739 with prior cardiac arrest 17,158 with history of sustained VT 5,725 with < 1 yr continuous eligibility 5,248 with age < 66 years old 2,045 with no device type information 122,562 ICD records linked to MedPAR records 66,974 patients eligible

35. Implantable Cardioverter Defibrillator (ICD) Ventricular arrhythmia is common among heart failure (HF) patients 50-80% non-sustained ventricular tachycardia (VT) 5% sustained VT or ventricular fibrillation (VF) (fatal) Presence of HF increases the sudden death rate 5.5-fold in both men and women (Framingham heart study) 35

36. Implantable Cardioverter Defibrillator (ICD) ICDs have shown to be beneficial as a primary prevention of sudden cardiac death (SCD) among HF patients with systolic dysfunction in trials (primary prevention of SCD) National Coverage Decision (NCD) in Jan 2005 CMS expanded the coverage for ICD implantation for primary prevention 36

37. Important Covariates

38. Outcome Definitions

39. Characteristics by Number of Hospitalization.