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Implantable cardioverter-defibrillators (ICDs) reduce mortality risk in primary prevention, although the evidence is somewhat mixed for nonischemic versus nonischemic cardiomyopathy, a meta-analysis suggested.

with ICD therapy than conventional care overall (21.37% versus 28.26%, HR 0.81, 95% CI 0.70-0.94), Eliano P. Navarese, MD, PhD, of Inova Heart and Vascular Institute in Falls Church, Va., and colleagues reported in the Annals of Internal Medicine.

Although the magnitude of reduction was similar in nonischemic (HR 0.81, 95% CI 0.72-0.91) and ischemic disease (HR 0.82, 95% CI 0.63-1.06), it wasn't statistically significant in the latter group.

For sudden death, ICDs held an overall advantage (4.39% versus 12.15%, HR 0.41, 95% CI 0.30-0.56) that was similar in magnitude for ischemic and nonischemic cases but, this time, only significant for ischemic disease (HR 0.39, 95% CI 0.23-0.68, and HR 0.44, 95% CI 0.17-1.12, respectively).

The researchers pointed to the controversy raised by the DANISH trial, which found no mortality advantage to primary prevention ICDs in nonischemic symptomatic heart failure with reduced ejection fraction, as the reason for their meta-analysis.

Navarese's group chalked up the lack of overall mortality significance for the ischemic group up to two early post–MI treatment trials (DINAMIT and IRIS) and the immediate post–coronary bypass surgery treatment trial (CABG Patch) showing no survival benefit with ICD therapy.

Competing causes of death likely diluted the effects of ICDs in these trials, the researchers suggested. "This interpretation is supported by the lower incidence of arrhythmic death than of other causes during the first 18 months after myocardial infarction, as indicated by the results of our subgroup and sensitivity analyses showing significant survival benefit with later but not earlier ICD placement," they wrote.

As to the lack of difference in sudden cardiac death -- the main rationale for ICD use -- in the nonischemic group, the researchers explained this by the dominance of DANISH in terms of numbers against a backdrop of relatively fewer trial participants than in the ischemic disease trials as well as the lower incidence of cardiac arrhythmic death and the relatively few sudden deaths in the group with nonischemic disease (90 in total).

The meta-analysis included study-level data from 11 trials with a total 8,716 patients, of which four trials were in nonischemic cardiomyopathy only, six looked only at ischemic cardiomyopathy, and one included both. Limitations included the heterogeneous timing of ICD placement, heterogeneous pharmacologic and resynchronization co-interventions, and different eras covered by the trials.

Ongoing trials that may help clear up controversy in this field, the researchers noted, include the I-70 trial of ICDs in patients older than 70 years and REVIVED-BCIS2 addressing percutaneous revascularization versus optimal medical therapy in ICD candidates for primary prevention of sudden cardiac death from ventricular arrhythmias.

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