DINAMIT published: Wait a while after MI before considering ICD

December 08, 2004

Frankfurt, Germany - Results of the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT)the first randomized controlled study to assess the impact of ICD therapy very early after MIhave been published in the December 9, 2004 issue of the New England Journal of Medicine.[1] The findings suggest that patients should wait until everything is stabilized following an MIa period of perhaps four to six weeksbefore prophylactic implantation of an ICD is considered.

First reported at the American College of Cardiology meeting in New Orleans in March, the DINAMIT results are similar to other trials of ICD therapy in that they show a 50% reduction in the rate of death from arrhythmia in patients who receive ICDs. But in contrast to most previous studies, the overall mortality between the ICD and control group was not different, report Dr Stefan Hohnloser (JW Goethe-University College, Frankfurt, Germany) and colleagues in their paper.

Two editorials accompany the DINAMIT paper. In the first, Dr Anne M Gillis (Libin Cardiovascular Institute, Calgary, AB) says, "This important clinical trial identifies a group of patients with risk factors for sudden death from cardiac causes in whom ICD therapy may not provide a survival benefit."[2]

In the second, Drs Sandeep Jauhar and David J Slotwiner (Long Island Jewish Medical Center, New Hyde Park, NY) discuss how big a role economics should play in deciding who gets a defibrillator [see sidebar].[3]

Transforming sudden death into eventual death?

As reported by heart wire , DINAMIT randomized 674 patients within 40 days of an acute MI to best medical therapy with or without an ICD and followed them for a mean of 2.5 years. There was no difference in overall mortality between the two groups; of the 120 who died, 62 were in the ICD group and 58 in the control group (hazard ratio for death in the ICD group 1.08; p=0.66).

There were 12 deaths due to arrhythmia in the ICD group, compared with 29 among controls (HR for ICD group 0.42; p=0.009). In contrast, there were 50 deaths from nonarrhythmic causes in the ICD group but only 29 in the controls (HR for ICD group 1.75; p=0.02).

"The reason for the unexpected and unprecedented increase in mortality from causes other than arrhythmia in patients assigned to receive an ICD is not clear," say Hohnloser et al. "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."

"It has been speculated that ICDs might, by shocking ventricular fibrillation, merely transform sudden death to eventual death from pump failure, without significantly prolonging life, especially when ventricular fibrillation is occurring in a patient with end-stage heart failure or a large acute myocardial infarction," they add.

In fact, a subsequent analysis by the DINAMIT investigators reported last month at the American Heart Association (AHA) meeting showed that the excess in nonsudden deaths in the ICD group were primarily confined to those who also received shocks from their defibrillator. So in those receiving ICDs soon after MI, arrhythmias that are aborted by the ICD could point to patients who are destined to die soon of other cardiac causes, they suggest.

Survival for a given time post-MI could identify who will benefit from ICDs

This indicates that those identified as potentially needing a defibrillator in the first six weeks after a heart attack will not benefit from the device, one of the DINAMIT researchers, Dr Paul Dorian (St Michael's Hospital, Toronto, ON), told heart wire at the AHA meeting. But survival long enough after an infarction could select out patients who will show an all-cause mortality decrease if they then receive an ICD, as demonstrated in primary-prevention defibrillator trials of patients with more remote histories of MI.

Gillis agrees in her editorial"the temporal proximity to the index MI influenced the outcomes in DINAMIT"and points to a retrospective analysis of the MADIT II trial that showed that those with an MI that had occurred at least 18 months previously benefited greatly from the ICD, whereas those with a more recent MI (less than 18 months) did not.

Heart-failure expert Dr William T Abraham (Ohio State University, Columbus, OH) told heart wire : "I think we must adopt a fully evidenced-based approach to the selection of ICD candidates. MADIT II, DEFINITE, and SCD-HeFT clearly support the use of ICDs as primary prevention in patients with a remote MI and left ventricular systolic dysfunction [LVSD](MADIT II and SCD-HeFT) and in patients with established chronic LVSD of either ischemic or nonischemic etiology (DEFINITE, SCD-HeFT)."

 
If the MI has occurred within 30 days, they should not [receive an ICD].
 

But, Abraham continues, "On the other hand, DINAMIT suggests that patients with a recent MI and acute-onset LVSD do not benefit from ICDs. I think the cutoff should be that used prospectively in the inclusion of patients in these trials. That was 30 days. So, patients whose MI is older than 30 days or have chronic LVSD with an EF <30% to 35% should receive an ICD. If the MI has occurred within 30 days, they should not (for primary prevention)."

Gillis elaborates on the subject of patient selection in her editorial. She notes that all of the patients included in DINAMIT had an indicator of autonomic dysfunctionabnormal heart rate variability, an elevated heart rate at rest, or both. "The measures of autonomic dysfunction used by the DINAMIT investigators are inexpensive and available by means of current Holter technology. Thus, these tools can be readily used in clinical practice to identify patients who are unlikely to benefit from prophylactic implantation of an ICD."

"The more difficult challenge confronting us will be to develop better risk-stratification techniquestechniques that will enable us to identify the patients at high risk for sudden death who are most likely to benefit from prophylactic use of an ICD. Such an approach will make the use of ICD therapy more cost-effective," she concludes.



Dollars and sense: Can ICDs be justified economically?

In their editorial, Jauhar and Slotwiner say the findings of Hohnloser et al "will further complicate the matter" of how government will pay for ICDs. They observe that in 2003, 150 000 defibrillators were implanted in the US and that the recent new CMS reimbursement guidelines "will dramatically increase the number of patients for whom prophylactic implantation of an ICD would be covered by Medicare."

Economic analysis must be performed over the lifespan of a defibrillator to assess cost effectiveness properly, they note. "Short-term analyses are biased against medical devices, which carry enormous up-front costs." They suggest that a national registry could prove useful in this regard, as it would allow for longer patient follow-up and better real-world estimates of costs and benefits. "The CMS is awaiting recommendations from the Heart Rhythm Society on the development of such a registry," they note.

A cost-effectiveness analysis of SCD-HeFT, presented last month at the AHA meeting, showed a cost of about $33 000 per life-year saved for ICDs. "Not cheap, to be sure, but still justifiable from the standpoint of cost effectiveness." As a comparison, renal dialysis has set a sort of standard for cost-effective medical therapy at roughly $50 000 per life-year saved, they explain.

Abraham told heart wire , "The cost efficacy of ICDs is acceptable when compared with other life-sustaining therapies in cardiovascular disease patients."

Nevertheless, Jauhar and Slotwiner warn that "even though reimbursement guidelines for prophylactic use of ICDs are expanding . . . with further cost-effectiveness studies, longer trials, and better ways of identifying the patients who will benefit most, physicians must remain vigilant about justifying device therapy or risk having this therapy taken away from their patients."


The DINAMIT study was supported by a grant from St Jude Medical. Hohnloser, Kuck, Dorian, and Connolly are consultants to and have received lecture fees from St Jude Medical. Gillis has served on a physician advisory board for Medtronic and has received lecture fees from Medtronic and Guidant. Abraham has received research grants and/or speaker honoraria from Medtronic, Guidant, and St Jude.

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