1. EP Show – Aug 2003 ICDs – Primary prevention The EP Show: Which ICD for which patient? Part 2: Primary prevention Eric Prystowsky MD Director, Clinical Electrophysiology Laboratory St Vincent Hospital Indianapolis, IN Helmut Klein MD Head of Division of Cardiology Otto-von-Guericke Universität Magdeburg Magdeburg, Germany Paul Dorian MD Professor of Medicine Division of cardiology St Michael's Hospital Toronto, ON

2. EP Show – Aug 2003 ICDs – Primary prevention Major trials Primary prevention patients MUSTT: CAD EF <40% MADIT I: CAD EF <35% MADIT II: CAD EF <30%

3. EP Show – Aug 2003 ICDs – Primary prevention Control ICD ICD benefit 0 10 20 30 40 MADIT II 2-year all-cause mortality (%) 31% MUSTT MADIT I 54% 51% Relative reduction

4. EP Show – Aug 2003 ICDs – Primary prevention EF <40% CAD Spontaneous nonsustained ventricular tachycardia (VT-NS) MUSTT ICDs (n=161) Drug therapy (n=153) p 24%55%<0.001 Buxton et al. N Engl J Med 1999;341(25):1882-90. Entry Criteria Total mortality (5 years)

5. EP Show – Aug 2003 ICDs – Primary prevention Control ICD ICD benefit 0 10 20 30 40 MADIT II 2-year all-cause mortality (%) 31% MUSTT MADIT 54% 51% Relative reduction

6. EP Show – Aug 2003 ICDs – Primary prevention Nonischemic

7. EP Show – Aug 2003 ICDs – Primary prevention Two questions Why has it not been possible to show a survival benefit with ICDs for nonischemic cardiomyopathy patients? Why haven't more ICDs been used in primary prevention in light of the positive data from trials? Prystowsky

8. EP Show – Aug 2003 ICDs – Primary prevention Nonischemic sudden death The mechanism for sudden death may not be the same in nonischemic patients; they are less likely to have a new ischemic event The intermediate term prognosis for nonischemic patients seems to be better Arrhythmia mechanisms may be different Beta blockers may be more effective ICDs may give less "bang for the buck" Dorian

9. EP Show – Aug 2003 ICDs – Primary prevention Jury is still out "We have to be very careful to remember that absence of proof is not the same as proof of absence." It is not yet proven that patients with dilated cardiomyopathy benefit from ICDs as primary prophylaxis, but [there is] also no proof ICDs are useless in this population Numerous upcoming trials may shed further light on the issue Dorian

10. EP Show – Aug 2003 ICDs – Primary prevention Primary prevention "Clearly we don't know everything we need to know about the magnitude of benefit from implanted defibrillators" Few doubt ICDs are effective The question is the likelihood of a patient actually suffering sudden death If small, the overall benefit is small If large, the overall benefit is large Dorian

11. EP Show – Aug 2003 ICDs – Primary prevention Insurance metaphor A wood house heated by coal or wood needs good fire insurance, while a brick house not heated often doesn't need fire insurance "How likely do we think it is that patients at potential risk for sudden death will actually have ventricular defibrillation or VT and be rescued by their defibrillator?" Dorian

12. EP Show – Aug 2003 ICDs – Primary prevention CMS decision CMS did a subgroup analysis of MADIT II to give only partial coverage of ICDs—similar to the house metaphor With limited resources one must pick the patients who clearly will get the most benefit "If defibrillators cost a buck a piece, we wouldn't have the argument." Prystowsky

13. EP Show – Aug 2003 ICDs – Primary prevention ICDs in Europe Why are there different approaches to ICDs in Germany and France? "It's more a philosophic issue than a medical issue." "It doesn't make sense that there is a difference between France and Germany and Italy; I cannot explain this." Klein

14. EP Show – Aug 2003 ICDs – Primary prevention Nonischemic cardiomyopathy The progress of nonischemic cardiomyopathy is very difficult to predict Patients with long-lasting nonsustained VT have a worse prognosis We tend to give long-lasting nonsustained VT patients ICDs, even when they are nonischemic A personal opinion Klein

15. EP Show – Aug 2003 ICDs – Primary prevention Need more parameters More parameters [are needed] to judge risk in nonischemic patients because they have a high risk of sudden death There is the parameter of nonsustained VT indicating higher risk Klein

16. EP Show – Aug 2003 ICDs – Primary prevention Primary prevention So far in Germany, any patient meeting the criteria have received an ICD, but this is changing toward a more careful husbanding of resources "We have had no problems so far, but it's getting worse and we will probably be forced to do so." Klein

17. EP Show – Aug 2003 ICDs – Primary prevention CMS coverage CMS decided to provide reimbursement for patients with MADIT II criteria but only those with a QRS duration of >120 ms "Frankly, having reviewed the data in the literature so far, that does seem to at least be the wood house. It doesn't mean we shouldn't be protecting the nonwooden houses." Prystowsky

18. EP Show – Aug 2003 ICDs – Primary prevention Optimal therapy "We believe strongly that patients should be considered for prophylactic ICD if and only if their other therapies have been absolutely optimized." In a practical sense, this means many patients recommended for ICDs are ruled out by this more stringent approach Dorian

19. EP Show – Aug 2003 ICDs – Primary prevention MIRACLE End pointControl group 95% CICRT group 95% CIp Quality-of-life score -11.0-16 to -7-17.5-21 to -140.02 NYHA class0-1 to 0-1 to –10.007 Change in 6- minute walk distance (m) 5343 to 755544 to 790.36 Young JB et al. JAMA 2003; 289:2685-2694.

20. EP Show – Aug 2003 ICDs – Primary prevention COMPANION MeasureCRT (%) CRT-ICD (%) Mortality and hospitalization 19 Mortality23.943.4 Relative reduction at 12 months: compared with control arm ACC 2003

21. EP Show – Aug 2003 ICDs – Primary prevention Biventricular ICD COMPANION showed that resynchronization improves quality of life and performance, but only the defibrillator improves the survival "You cannot prevent sudden death by just improving ventricular function.... And if I have to make the choice, I certainly would use the combined device in coronary artery disease patients." Klein

22. EP Show – Aug 2003 ICDs – Primary prevention Biventricular pacemakers "I have yet to implant a biventricular pacemaker [for this group of people]." The data showing an advantage in preventing sudden death with the ICD function are very clear "Am I just being too aggressive?" Prystowsky

23. EP Show – Aug 2003 ICDs – Primary prevention Changing approach "Our thinking has evolved in this topic." We started doing a number of pacemaker- only devices, but evidence is mounting that improving ventricular function has only modest effects in preventing arrhythmia The extra risks and costs of adding the ICD function are not dramatic, and we are implanting more biventricular ICDs Dorian

24. EP Show – Aug 2003 ICDs – Primary prevention Choosing patients Patients who clearly are in severe heart failure despite optimal medical treatment we tend to give biventricular ICDs Those who have QRS of 120 or so but no severe heart failure might not get the ICD function Klein

25. EP Show – Aug 2003 ICDs – Primary prevention The broader view "It's important to not just see the data as they are published but also to be able to put them in context with a world of experience." Prystowsky

26. EP Show – Aug 2003 ICDs – Primary prevention Secondary prevention Patients with documented cardiac arrest, sustained VT, syncope in the EP lab Randomized trials point toward ICDs as therapy for these patients DAVID trial suggests not pacing the ventricle, selecting which device is left to the physician Prystowsky

27. EP Show – Aug 2003 ICDs – Primary prevention Primary prevention Randomized trials show that in ischemic heart disease ICDs are the best choice for therapy For the nonischemic patients, the data are still not in and more data are needed Depending on your budget, how narrow your selection process is will vary Prystowsky

28. EP Show – Aug 2003 ICDs – Primary prevention Biventricular devices The biventricular ICD prolongs life, not just a biventricular pacemaker The selection for a given patient will depend on multiple factors There are still situations where a doctor or investigator may pick a biventricular pacemaker only Prystowsky

29. EP Show – Aug 2003 ICDs – Primary prevention The EP Show: Which ICD for which patient? Part 2: Primary prevention Eric Prystowsky MD Director, Clinical Electrophysiology Laboratory St Vincent Hospital Indianapolis, IN Helmut Klein MD Head of Division of Cardiology Otto-von-Guericke Universität Magdeburg Magdeburg, Germany Paul Dorian MD Professor of Medicine Division of cardiology St Michael's Hospital Toronto, ON