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More data needed for the use of ICDs in patients with non-ischaemic heart failure

The European Society of Cardiology (ESC) Guidelines for the diagnosis and treatment of acute and chronic heart failure give the use of an implantable cardioverter defibrillator (ICD) in patients with a non-ischaemic heart failure a Class I, Level B recommendation. However, last year, the DANISH study (to assess the efficacy of ICDs in patients with non-ischaemic heart failure on mortality) cast doubt on this recommendation when it indicated that ICDs did not significantly reduce all-cause mortality in this group of patients.

Device Therapy
Implantable Cardioverter \ Defibrillator
Arrhythmias and Device Therapy
Heart Failure

DANISH investigators Professor Lars Køber (Department of Cardiology, Rigshospitalet, Copenhagen, Denmark) and others report in The New England Journal of Medicine that prior to their study, there was limited evidence for the use of ICDs in patients with non-ischaemic heart failure. They note that while the SCD-HeFT (Sudden cardiac death in heart failure) trial did show a benefit with ICDs in this patient population, this was “confined to patients in New York Heart Association (NYHA) class II” and, more importantly, “medical treatment for heart failure has changed since SCD-HeFT was conducted”.

Therefore, seeking to provide more evidence for this area, Køber et al randomised symptomatic patients (NYHA class II or III or class IV if cardiac resynchronisation therapy [CRT] was planned) with non-ischaemic heart failure and increased level of N-terminal pro-brain natriuretic (NT-proBNP) to undergo ICD implantation or usual care. The primary endpoint was death from any cause, with secondary outcomes being sudden cardiac death, cardiovascular death, resuscitated cardiac arrest or sustained ventricular tachycardia, and change from baseline in quality of life.

Of 1,116 patients enrolled into the DANISH study between February 2008 and June 2014, 556 were assigned to ICD implantation and 560 were assigned to usual care. Overall, 645 patients either had an indication for CRT or had a pre-existing CRT—with 322 being assigned to an ICD and 323 being assigned to the control group.

At the mean follow-up period of 67.6 months, death from any cause had occurred in 21.6% of patients in the ICD group and in 23.4% of patients in the control group; a non-significant difference (p=0.28). There was also no significant difference between groups in terms of cardiovascular death: 13.8% for the ICD group vs. 17% for the control group (p=0.10). However, Køber et al report: “Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (p=0.005).” They add that the effect of ICD implantation was independent of CRT status.

Noting that previous studies have showed a benefit of ICDs in patients with ischaemic heart failure, the authors comment: “Patients with non-ischaemic heart failure may be less prone to death from arrhythmia than patients with ischaemic heart failure, but better medical treatment and CRT also may have reduced the risk of death from arrhythmia for all patients with 
heart failure.”

Doctor Nikolaos Dagres (Department of Electrophysiology, University Leipzig - Heart Center, Leipzig, Germany), who is the European Heart Rhythm Association (EHRA) Scientific Initiatives Committee Chair, agrees with the idea that improved medical treatment and the effect of CRT—“since the percentage of patients with CRT was high in DANISH”—may explain the results. He told Congress News that the balance between sudden cardiac death and non-sudden cardiac death as causes of death in the study may be another factor.

“With a diminishing proportion of sudden cardiac death and consequent increase of non-sudden cardiac death as the cause of the death, the benefit from the reduction of sudden cardiac death for the improvement of survival will get smaller. Thus, the ICD reduced sudden cardiac death but this effect was—in absolute numbers—too small to translate to a reduction of overall mortality,” Dr. Dagres explained.

Although there was no overall benefit with ICDs in terms of all-cause death, subgroup analysis showed that ICDs were associated with a significant reduction in all-cause death in younger patients (younger than 68 years); p=0.01 for the comparison. Køber et al report: “The subgroup data that suggest a lower likelihood of benefit in older patients might be used as an argument for not implanting ICDs in elderly, frail patients. Also, the benefit of ICD implantation with respect to sudden cardiac death that was seen in our trial is convincing, and patients who are not expected to die from other causes may be good candidates for ICD implantation.”

For Dr. Dagres, the balance between the numbers of sudden cardiac deaths and non-sudden cardiac deaths in the study may again explain the differences in benefit of ICDs between younger and older patients.

He added: “We have to await more data from the analysis of DANISH to draw any further conclusions about that. Also, we must keep in mind that we cannot exclude the possibility of some recruitment bias with physicians being more reluctant to include younger patients in the study; however, that is speculative.”

When the DANISH study was presented at the ESC Congress last August, there was some discussion that that the current ESC recommendations should be amended. However, Prof. Køber told Congress News that challenging these recommendations would be difficult given the level B evidence status—which, by definition, indicates that limited populations have been studied and that there may be conflicting evidence for the benefit of an intervention. Similarly, Dr. Dagres said that “it would be too early to revise the guidelines” in lieu of more evidence. “However, we certainly need new evidence on which we will base the treatment of patients in the years to come,” he commented.

Prof. Køber agrees that more data are needed, stating that “prospective randomised trials that test other methods (aside from ICD) to determine who would benefit the most from ICDs to better markers of sudden cardiac death, and to challenge the guidelines for managing patients with ischaemic heart disease are needed.” According to Dr. Dagres, EHRA will be further exploring the role of ICD as primary prevention in patients with ischaemic cardiomyopathy with the RESET-SCD study.

Today, a debate session—“Indications for ICDs in 2017”—will further explore the issues raised by the DANISH study. Professor Jens Cosedis Nielsen (Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark) will propose that “After DANISH: primary prevention of SCD with the ICD in NICM is dead!” while Professor Michael R Gold (Division of Cardiology, Medical University of South Carolina, Charleston, USA) will provide the counter argument with his presentation “After DANISH: primary prevention of SCD with the ICD in NICM is still alive!”. Furthermore, Professor Petr Neuzil (Cardiology Department, Na Homolce Hospital, Prague, Czech Republic) will be giving the “pro” side of the proposition for “SC ICD for most patients without pacing indication” with Assistant Professor Thomas Mungler (Division of Cardiovascular Diseases, Mayo Clinic, Rochester, USA) giving the “contra” side.

Indications for ICDs in 2017

Sunday 18 June at 14:00, room SOKOLOV

View the programme