EP show – June 2004

EP show

The EP show:Risk stratification for sudden death

Eric Prystowsky MDDirector, Clinical Electrophysiology Laboratory

St Vincent Hospital Indianapolis, IN

Arthur Moss MDProfessor of Medicine and CardiologyUniversity of RochesterRochester, NY

Michael Gold MDChief, Division of CardiologyMedical University South CarolinaCharleston, SC

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Risk stratification for sudden death

EP show – June 2004

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Historical look at early markers

•Began during the mid-1980s with a prospective study of about 1000 postinfarction patients

•Measured 24-hour Holter recordings for ventricular premature beat frequency

•Determined ejection fraction

•Ascertained several other routine clinical parameters

Moss

EP show – June 2004

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Historical look at early markers

•Found inverse relationship between the ejection fraction and total mortality as well as sudden death

•Cut point between 30% and 40%

•Recent studies, including MADIT I and II, grew out of this early

work

Moss

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Serial electrophysiology testing

•Mechanistically driven

•Sudden death in postinfarction patients predominately due to ventricular tachycardia

• If you could induce ventricular tachycardia and introduce a

drug that suppresses this ability, you could monitor efficacy

Gold

EP show – June 2004

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Reviewing CAST

•Cardiac Arrhythmia Suppression Trial (CAST)

•Large randomized trial that looked at whether suppressing ventricular ectopy after MI reduces sudden death

•Trial stopped because antiarrhythmic agents associated with increased mortality

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Reviewing CAST

"This set the stage for moving from antiarrhythmic agents to device therapy."

Moss

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Reviewing CAST

•Could these results be related to the drugs selected?

•Subsequent trials confirmed that this was not the case

Prystowsky

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MADIT I•Would an ICD or conventional therapy improve

survival in this high-risk population?

•Randomly assigned 196 patients with prior MI and:

• NYHA functional class 1, 2, or 3

• A left ventricular ejection fraction <35%

• An episode of asymptomatic unsustained ventricular tachycardia

• Inducible, nonsuppressible ventricular tachyarrhythmia on electrophysiologic study

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MADIT I findings

GroupTotal deaths

Cardiac deaths

Defibrillator 15 11

Conventional therapy 39 27*Average 27-month follow-up

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MADIT I

• In high-risk patients with prior MI, prophylactic therapy with an ICD leads to improved survival compared with conventional medical therapy

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MUSTT

•Multicenter Unsustained Tachycardia Trial (MUSTT), a randomized controlled trial

•Can electrophysiologically guided antiarrhythmic therapy reduce the risk of sudden death?

•Looked at coronary artery disease patients with a left ventricular ejection fraction <40% and asymptomatic unsustained ventricular tachycardia

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MUSTT

End point Cardiac arrest or arrhythmia death

EP-guided therapy (%)

25

No antiarrhythmic therapy (%)

32

Relative risk 0.73

95% CI 0.53-0.99

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MUSTT

•Therapy with implantable defibrillators, but not with antiarrhythmic drugs, reduces the risk of sudden death in high-risk patients with coronary disease

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Unsustained VT

"I think it's a relatively weak risk stratifier. And as you point out, it was both frustrating and cumbersome."

Gold

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MADIT II

•Randomized trial evaluating the effect of an implantable defibrillator on survival

•1232 patients with prior MI and a left ventricular ejection fraction of <30%

•Patients randomly assigned in a 3:2 ratio to receive ICD or conventional medical therapy

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MADIT mortality rates

19.8

14.2

0

2

4

6

8

10

12

14

16

18

20

Mortality

Conventional therapy

Defibrillator

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MADIT II

"This really introduced a simplified stratification approach."

Moss

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MADIT II and CMS

"They took a conservative position and said that they were going to reimburse only for MADIT II patients who had a QRS duration >120 milliseconds and that they would revisit this when SCD-HeFT data were presented."

Moss

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SCD-HeFT

•Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)

•Largest of the trials involving ICD therapy with a longer patient follow-up than previous studies

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SCD-HeFT

•Compared all-cause mortality in >2500 patients

•With NYHA class 2 to 3 HF

•LVEF <35%

•Patients randomized to receive ICD, amiodarone, or placebo on top of standard medical therapy

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SCD-HeFT all-cause mortality

0

5

10

15

20

25

30

35

3 year(% )

5 year(% )

ICDAmiodaronePlacebo

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SCD-HeFT

• ICD cuts all-cause mortality by 23% in NYHA class 2 to 3 heart failure

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What's a payer to do?

"The trials were designed specifically to answer the major question of defibrillators and their role to reduce total mortality. I think the trials, as you point out, are concordant in that regard, and I think that it would be reasonable that that would be an indicationfor paying."

Gold

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What's a payer to do?

"Getting into subsets when it's not really prespecified that's what you're looking for is potentially very treacherous and can be misleading."

Moss

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The future

•Many have become cynical as noninvasive test after noninvasive test failed to live up to its expectations

•But I remain optimistic

Gold

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Question

Are there patients in MADIT II who are:

• "Too healthy" to benefit from an ICD?

• "Too sick" for one?

Prystowsky

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Latest look at MADIT II

•The benefit from ICD was entirely in the patients who carried one or more risk factors

•The 20% of the population that carried no risk factors achieved no benefit whatsoever

Moss

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Summary

•Several decades of research have put risk stratifiers to the test

•Ejection fraction remains supreme as a noninvasive test

•We've identified the benefactors of ICD therapy

•And realized that antiarrhythmic drugs to prevent sudden death are not as important as once thought

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In conclusion

•Despite so many noninvasive tests failing to live up to expectations, many still show promise

•Hot off the press! New soon-to-be-published data will show that combinations of risk stratifiers may help pinpoint patients who will

derive the most and least benefit from an ICD

Prystowsky