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
EP show – June 2004
EP show
Risk stratification for sudden death
EP show – June 2004
EP show
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
EP show
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
EP show – June 2004
EP show
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
EP show
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
EP show – June 2004
EP show
Reviewing CAST
"This set the stage for moving from antiarrhythmic agents to device therapy."
Moss
EP show – June 2004
EP show
Reviewing CAST
•Could these results be related to the drugs selected?
•Subsequent trials confirmed that this was not the case
Prystowsky
EP show – June 2004
EP show
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
EP show – June 2004
EP show
MADIT I findings
GroupTotal deaths
Cardiac deaths
Defibrillator 15 11
Conventional therapy 39 27*Average 27-month follow-up
EP show – June 2004
EP show
MADIT I
• In high-risk patients with prior MI, prophylactic therapy with an ICD leads to improved survival compared with conventional medical therapy
EP show – June 2004
EP show
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
EP show – June 2004
EP show
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
EP show – June 2004
EP show
MUSTT
•Therapy with implantable defibrillators, but not with antiarrhythmic drugs, reduces the risk of sudden death in high-risk patients with coronary disease
EP show – June 2004
EP show
Unsustained VT
"I think it's a relatively weak risk stratifier. And as you point out, it was both frustrating and cumbersome."
Gold
EP show – June 2004
EP show
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
EP show – June 2004
EP show
MADIT mortality rates
19.8
14.2
0
2
4
6
8
10
12
14
16
18
20
Mortality
Conventional therapy
Defibrillator
EP show – June 2004
EP show
MADIT II
"This really introduced a simplified stratification approach."
Moss
EP show – June 2004
EP show
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
EP show – June 2004
EP show
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
EP show – June 2004
EP show
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
EP show – June 2004
EP show
SCD-HeFT all-cause mortality
0
5
10
15
20
25
30
35
3 year(% )
5 year(% )
ICDAmiodaronePlacebo
EP show – June 2004
EP show
SCD-HeFT
• ICD cuts all-cause mortality by 23% in NYHA class 2 to 3 heart failure
EP show – June 2004
EP show
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
EP show – June 2004
EP show
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
EP show – June 2004
EP show
The future
•Many have become cynical as noninvasive test after noninvasive test failed to live up to its expectations
•But I remain optimistic
Gold
EP show – June 2004
EP show
Question
Are there patients in MADIT II who are:
• "Too healthy" to benefit from an ICD?
• "Too sick" for one?
Prystowsky
EP show – June 2004
EP show
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
EP show – June 2004
EP show
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
EP show – June 2004
EP show
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