ESC: No Mortality Benefit With ICD in Nonischemic HF

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ROME -- Implanting cardiac defibrillators (ICDs) in patients with systolic heart failure not due to coronary artery disease did not reduce all-cause mortality compared with usual, a finding that could change clinical practice.

In a head-to-head trial of patients with left ventricular ejection fractions (EF) of 35% or less comparing ICD (n=556) with usual care (n=560), 120 patients in the ICD arm died during more than 5 years of follow-up versus 131 deaths in the usual care arm (P=0.28).

In both groups 58% of patients received a biventricular pacemaker.

Lars Køber, MD, DMSc, of Rigshospitalet, University Hospital, in Copenhagen reported results from the DANISH study in the first Hot Line session at the European Society of Cardiology (ESC) annual meeting.

During a press conference where the findings were discussed, Køber said there was a clear interaction with age: patients younger than 68 had a significantly lower all cause mortality (HR 0.64 (95% CI 0.46-0.91) P=0.011), while older patients had a higher mortality rate (HR 1.2(0.81-1.72) P=0.38. The P value for interaction with age was 0.009.

The explanation, he said, was simple: "If you are older and you are likely to have more comorbidities and therefore the risk of dying from any cause is greater."

Mariell L. Jessup, MD, medical director of the Penn Heart and Vascular Center, said the findings confirm "what we knew: ICDs prevent sudden cardiac death."

But Jessup, who co-chaired the press conference and is a member of the writing committees for both U.S. and European heart failure guidelines said the DANISH findings were unlikely to change current guidelines.

The results were simultaneously published online in the New England Journal of Medicine.

"Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio 0.50, 95% CI 0.31 to 0.82; P =0.005)," Køber and colleagues wrote. "Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29)."

During a press conference Saturday -- before the results were announced -- Steen Dalby Kristensen, MD, research professor at Aarhus University in Denmark, said "the DANISH study is big. If it is negative, I think it will be debated again -- together with results from smaller trials -- whether we really should continue to treat patients with nonischemic heart failure with ICDs. This is a trial that could really change practice."

Kristensen chairs the ESC press committee.

But Clyde Yancy, MD, chief of cardiology at Northwestern University Feinberg School of Medicine in Chicago, cautioned against overinterpreting the results. "In a prospective study where coronary artery disease was not the cause of heart failure, we saw a lessor benefit in all-cause mortality, but there was still more than a 50% reduction in sudden cardiac deaths."

Yancy, who was not involved in the study, said he agreed with the headline of an accompanying editorial by John J.V. McMurray, MD, of the University of Glasgow: "ICDs in Heart Failure -- Time for a Rethink?"

Click here for MedPage Today's ESC 2016 video page, which includes comments from authors of the Hot Lines trials, and leading cardiologists from around the world providing daily commentary.

In his editorial, McMurray wrote that the "absolute benefit of ICDs in a typical and well-treated population with heart failure might be small. ICDs are expensive and not without adverse effects. It is, therefore, desirable to avoid their use in patients who are unlikely to obtain a worthwhile benefit."

Yancy told MedPage Today there were several reasons for his caution, but chief among those reasons was the unique nature of the study population, which was drawn from the Danish population and thus more homogenous, generically and economically, than a North American population. He also pointed out that the study "took a long time to enroll -- close to 6 years ... and enrollment was continued in order to maintain the power of the study." Such extensions are always "problematic," he said.

But perhaps the biggest red flag, according to Yancy, was the use of cardiac resynchronization therapy alone in 58% of the population, something that is extremely rare in the U.S.

The real take home, Yancy said, is that "the only marker we have for ICD use is EF, and that is such a crude measure with so much plasticity." Now is the time to redouble efforts to find better markers, and enhanced MRI may be the answer, he added.