1. EP Show – Dec 2003 ICDs – Primary prevention The EP Show: Guidelines and reimbursement at the crossroads: Primary prevention with ICDs Eric Prystowsky MD Director, Clinical Electrophysiology Laboratory St Vincent Hospital Indianapolis, IN Stephen Hammill MD Professor of Medicine Mayo Clinic College of Medicine Rochester, MN Jeremy Ruskin MD Director, Cardiac Arrhythmia Service Massachusetts General Hospital Boston, MA

2. EP Show – Dec 2003 ICDs – Primary prevention ICDs in Primary Prevention: MUSTT MADIT MADIT II CABG-Patch Topic

3. EP Show – Dec 2003 ICDs – Primary prevention MUSTT The Multicenter Unsustained Tachycardia Trial N Engl J Med 2002; 341:1882-90 CAD patients with EF <40% and nonsustained VT underwent EP testing If inducible, randomized to best medical therapy or antiarrhythmic treatment including an ICD Patients with sustained VT and an ICD had a marked reduction in mortality; those receiving drug therapy did not show a mortality benefit

4. EP Show – Dec 2003 ICDs – Primary prevention MADIT Multicenter Autonomic Defibrillator Implantation Trial N Engl J Med 1996; 335:1933-40 Patients with a history of MI, EF <35% nonsustained VT, sustained VT Randomized to best medical therapy (50% on amiodarone)or an ICD Approximately 50% reduction in mortality with the ICD

5. EP Show – Dec 2003 ICDs – Primary prevention CABG Patch 910 patients who underwent coronary artery bypass grafting, with EF <35%, randomized to an ICD or not Patients did not derive any benefit from the ICD during follow-up

6. EP Show – Dec 2003 ICDs – Primary prevention MADIT II Multicenter Autonomic Defibrillator Implantation Trial II N Engl J Med 2002; 346:877-83 1232 patients from 71 US centers and 5 European centers with a history of MI, EF <30%, randomized to an ICD or conventional medical therapy Patients with an ICD had a better survival outcome

7. EP Show – Dec 2003 ICDs – Primary prevention TrialICD group (%) Control group (%) RR (95% CI) MUSTT22450.49 (0.35-0.67) MADIT16390.41 (0.24-0.69) CABG Patch 23211.08 (0.84-1.39) MADIT II14200.71 (0.56-.92) Meta-analysis Ann Intern Med 2003; 138:445-52 All-cause mortality

8. EP Show – Dec 2003 ICDs – Primary prevention Definite answers MADIT, MUSTT Striking impact on mortality with ICD therapy No active patient recruitment; for patients meeting criteria we follow the guidelines from those two trials Only 15% to 20% of all ICD recipients Ruskin

9. EP Show – Dec 2003 ICDs – Primary prevention Reimbursement MADIT II Issues around reimbursement and patient selection Option of an ICD considered for MADIT- II patients meeting reimbursement criteria Ruskin

10. EP Show – Dec 2003 ICDs – Primary prevention Power of revascularization CABG Patch Speaks to the power of a complete revascularization procedure on risk for sudden death Inducibility at EP study allowed low-risk patients to get into the study Benefits of the ICD may have been diluted Ruskin

11. EP Show – Dec 2003 ICDs – Primary prevention Paradox Patients who never had VT or VF undergoing CABG have no additional benefit with ICD CABG alone is not enough in patients with sustained VT or cardiac arrest Prystowsky "A very good point." Ruskin

12. EP Show – Dec 2003 ICDs – Primary prevention Patient characteristics VT on the basis of scar or abnormal substrate around the scar: Revascularization alone does not eliminate VT, because it doesn't alter the substrate VF and well-preserved ventricular function: Revascularization is a very powerful intervention Ruskin

13. EP Show – Dec 2003 ICDs – Primary prevention Outcome predictors Three powerful independent predictors of favorable outcome in cardiac-arrest survivors: Ejection fraction ICD presence Revascularization

14. EP Show – Dec 2003 ICDs – Primary prevention Guidelines Why does MADIT I, with 196 patients, get a class 1 indication, whereas MADIT II, with over 1200 patients, only receives a class 2A indication? "I'm not sure that there's a clear reason." Perhaps today confirmatory trials are awaited "It seems that... people are setting the bar higher." Hammil

15. EP Show – Dec 2003 ICDs – Primary prevention Changing paradigms Why should we not go out looking for these patients? We have a way to save lives. Prystowsky A change in paradigm: "It took the American Heart a decade or longer to get people to thinking about 'what is your cholesterol level?' We are at that point with defibrillator treatment to prevent sudden death." Hammill

16. EP Show – Dec 2003 ICDs – Primary prevention Heart Rhythm Society Campaign: "Learn your EF" Part of the Heart Rhythm Foundation looking at several areas of rhythm disturbances, one of them sudden death, focusing on EF Stephen Hammill, incoming president, Heart Rhythm Society

17. EP Show – Dec 2003 ICDs – Primary prevention Patient eligibility Why are not many electrophysiologists literally beating the bushes for these patients? History of ICD therapy: a consistent but slow process of lowering resistance to implantation Concern at two levels: Not every patient meeting MADIT II- criteria fits the study population Huge cost Ruskin

18. EP Show – Dec 2003 ICDs – Primary prevention QRS Subgroup analysis: Wider QRS increased risk of an event improved benefit from the device QRS duration >120 ms QRS duration <120 ms Reduction in mortality with ICD (%) 5025

19. EP Show – Dec 2003 ICDs – Primary prevention Uncomfortable situation Studies are never powered to do these subgroup analyses with great confidence At our practice at the Mayo Clinic: Patient younger than 65 meeting MADIT- II criteria gets an ICD Patient 65 or older must have QRS >120 ms to get an ICD "It's an uncomfortable situation for the physician." Hammill

20. EP Show – Dec 2003 ICDs – Primary prevention Age discrimination "This is age discrimination. If somebody is 64 and 364 days, what's the difference to someone who is 65, except that one gets reimbursed and the other doesn't." Prystowsky "I agree, it's simply unacceptable." It puts physicians in an impossible situation. One has to work within reimbursement guidelines. Ruskin

21. EP Show – Dec 2003 ICDs – Primary prevention Subgroup analyses Subgroup analyses are hypotheses- generating exercises, not to be used as hard answers. Prystowsky "It doesn't seem scientifically reasonable for these subgroup analyses to be used in a pseudoscientific way to set reimbursement policies." Ruskin Excludes 70% of the Medicare population

22. EP Show – Dec 2003 ICDs – Primary prevention Rationing medical care Heart Database: Close to 78% of 1100 patients meeting MADIT-II criteria fell out once the QRS criterion was added "The worst of rationing medical care, because it is not rationing on anything other than age." Prystowsky

23. EP Show – Dec 2003 ICDs – Primary prevention Cardiomyopathy Patient: Nonsustained VT, EF 25% No guidelines that support placing a device Patients with dilated cardiomyopathy and nonsustained VT are not getting a device in our practice. Patients needing a biventricular pacemaker to treat HF who meet all necessary criteria will receive a biventricular ICD, based on the COMPANION trial. Hammill

24. EP Show – Dec 2003 ICDs – Primary prevention DEFINITE: Design DEFibrillators in Nonischemic Cardiomyopathy Treatment Evaluation 458 patients with LV dysfunction due to nonischemic dilated cardiomyopathy, EF <35%, and a history of spontaneous premature complexes or nonsustained VT Randomized to standard medical therapy plus ICD or medical therapy alone

25. EP Show – Dec 2003 ICDs – Primary prevention DEFINITE: Outcome p=0.06 AHA 2003

26. EP Show – Dec 2003 ICDs – Primary prevention DEFINITE: Comment Positive trial that was underpowered: more patients and longer follow-up needed 34% reduction in all-cause mortality More evidence that patients with nonischemic cardiomyopathy and severe LV dysfunction are at severe risk for sudden death and benefit from an ICD SCD-HeFT could provide more data

27. EP Show – Dec 2003 ICDs – Primary prevention Clinical practice I don't look for cardiomyopathy patients, but if they fall on my doorstep I do an EP study for induced sustained arrhythmia and implant a defibrillator. Prystowsky ICDs for Patients with familial cardiomyopathy Cardiomyopathy patients presenting with syncope Hammill

28. EP Show – Dec 2003 ICDs – Primary prevention ICDs in primary prevention: Wrap-up Review of all major trials in CAD put into perspective Applicability of trial results in clinical practice Reimbursement in conflict with true data in guidelines Moving in one other direction in the cardiomyopathy group "If SCD-HeFT comes out positive, it will push us very much in that direction." Prystowsky