April 2, 2009 (Orlando, Florida) — Patents who receive an implantable cardioverter defibrillator (ICD) within a month of acute MI, following testing that shows them to be at increased arrhythmic risk, have a reduced likelihood of sudden cardiac death (SCD) over the next several years but are more apt to die from other causes, suggests a randomized study reported at the American College of Cardiology 2009 Scientific Sessions , in which ICDs added to optimal medical therapy (OMT) in that early post-MI period had no effect on all-cause mortality over three years.
In some ways the findings support current proscriptions against implanting ICDs in that early post-MI period, which entered the guidelines based largely on the 2004 DINAMIT study , but in other ways they venture into new realms that complicate its relevance to current patient-eligibility criteria for primary-prevention device therapy.
The Immediate Risk Stratification Improves Survival (IRIS) trial entered about 900 patients within a month of an MI who had an LVEF <40% with a high heart rate, nonsustained ventricular tachycardia (NSVT) regardless of LVEF, or both sets of features. With low LVEF not mandated for getting into the study, many participants had systolic function greater than the primary-prevention ICD-eligibility threshold in the guidelines, observed Dr Gerhard Steinbeck (Ludwig Maximilians University, Munich, Germany) when presenting the study.
Even so, Steinbeck observed, the early risk stratification identified a post-MI population with an only "moderately reduced" ejection fraction who had substantial three-year risks of all-cause mortality and sudden cardiac death for whom an ICD made no survival difference.
As a panelist speaking after Steinbeck's presentation, Dr Richard L Page (University of Washington, Seattle) pointed out that a substantial number of patients in IRIS had an LVEF above 40%, but "we don't have trials to suggest that patients with preserved ejection fractions should receive an ICD as primary prevention."
Also, he said, "Sudden death appeared to be reduced, but nonsudden death was increased, and I have trouble understanding that. I'm not saying this is the reason, but I wonder whether defibrillation threshold testing [DFT] might have contributed," a reference to concerns that such testing in the early post-MI period might somehow compromise the myocardium and worsen outcomes.
Steinhart replied that there were no complications associated with DFT, and "we are quite sure that no excess mortality occurred when the ICD was implanted."
He offered his interpretation of the counterbalancing mortality end points: the patients whose ICDs prevented SCD went on to die of other causes--pump failure, for example. "There are other possible explanations. We have to look at the role of appropriate and inappropriate shocks and concomitant therapy," he said. "But I think the simple explanation is probably that VT/VF in the very early postinfarction period is not a determinant or cause of sudden cardiac death, it's just an indicator that picks out those patients who will die anyway, whatever you do."
The DINAMIT investigators speculated in 2004 in much the same way about their findings, which were similar to those in IRIS. Their study randomized 674 patients (LVEF <35) within 40 days after an acute MI to best medical therapy with or without an ICD. As reported at the time by heartwire, there was no difference in all-cause mortality between the two groups over an average of 2.5 years; the ICD group's significant reduction in SCD risk (p=0.009) was offset by its increased rate of nonarrhythmic death (p=0.02).
"The most likely explanation is that the patients 'saved' from an arrhythmia-related death by ICD therapy are also at high risk of death from other cardiac causes," they wrote. "ICDs might, by shocking ventricular fibrillation, merely transform sudden death to eventual death from pump failure, without significantly prolonging life."
IRIS enrolled patients within five to 31 days of their MI having screened them for the entry criteria for increased arrhythmic risk--that is, both an LVEF <40% and heart rate >90 bpm and/or NSVT at >150 bpm during Holter monitoring.
Randomization to therapy with an ICD on top of OMT made no significant overall impact on survival at 12, 24, or 36 months, yet it was associated with a significant drop in SCD (p=0.049) and a significant increase in non-SCD death (p=0.001) compared with the OMT-only group.
All-Cause Mortality at 36 Months by Treatment Group and Risk-Stratification Criteria in IRIS
|Risk-criteria group||ICD+OMT (%)||OMT only (%)||p|
|All patients (mean LVEF 35%), n=898||22.0||22.9||0.76|
|LVEF <40% and HR >90 bpm (mean LVEF 32%), n=602||24.6||25.0||0.91|
|NSVT >150 bpm (mean LVEF 41%), n=296||17.2||18.7||0.71|
"This trial did not test the same population of patients that receive defibrillators in the US and Europe," Dr Claudio D Schuger (Henry Ford Hospital, Detroit, MI) told heartwire . "This was a trial of implantation of a defibrillator immediately after myocardial infarction in patients of whom some have preserved left ventricular function." Schuger was moderator for the session in which the IRIS trial was presented.
"The speculation of the investigators is that [the ICD patients] exchanged one mode of death for another. What I personally fail to understand is, Why does that [effect] persist beyond the immediate primary event?" he said. "That goes against larger trials that have clearly demonstrated the benefit of the device in preventing sudden cardiac death in stable, not actively ischemic populations." He said further analyses of IRIS should look at what modes of non-SCD deaths were able to counter the ICD benefit against SCD.
IRIS was sponsored by AstraZeneca and the Medtronic Bakken Research Center. Steinbeck reports receiving lecture fees from AstraZeneca and Medtronic and being on a Medtronic advisory board. Page reports speaker's and consulting fees from Sanofi Aventis, Astellas Pharma, and Pfizer. Schuger reports consulting fees or honoraria from St Jude Medical, Boston Scientific, and Biosense Webster and research grants from Biosense Webster, St Jude Medical, and Medtronic.
Steinbeck G. A randomized study of the effects of defibrillator implantation early after myocardial infarction in high-risk patients on optimal medical therapy. American College of Cardiology 2009 Scientific Sessions; March 31, 2009; Orlando, FL. Late Breaking Clinical Trial IV: Arrhythmias/CHF.
Heartwire from Medscape © 2009 Medscape, LLC
Cite this: ACC 2009: IRIS Renews Focus on ICD Use Early Post-MI, Also Finds No Survival Benefit - Medscape - Apr 02, 2009.