Time to rethink ICD indications in non-ishaemic cardiomyopathy? Evidence from a meta-analysis across therapeutic eras.

Implantable cardioverter-defibrillators (ICDs) reduce sudden cardiac death (SCD) in non-ischaemic cardiomyopathy (NICM), but most evidence predates comprehensive guideline-directed medical therapy (GDMT). We quantified the relative and absolute survival benefit of primary-prevention ICDs in NICM across therapeutic eras and explored how contemporary GDMT modifies absolute benefit. We searched MEDLINE, Embase, and CENTRAL through March 2025 and included randomized controlled trials comparing prophylactic ICD implantation vs control in NICM with left ventricular ejection fraction ≤35%. Three trials (DEFINITE, SCD-HeFT NICM subgroup, and DANISH) contributed to the quantitative synthesis. ICD therapy reduced all-cause mortality (pooled hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.66-0.95) and SCD (HR 0.44, 95% CI 0.28-0.70). Five-year absolute risk reduction (ARR) was 5.9% (NNT 17) in SCD-HeFT NICM and 4.4% (NNT 23) in DANISH. Under a full-GDMT scenario parameterized from pharmacological randomized controlled trials, projected baseline risk was ∼11%, yielding ARR 2.31% (NNT 43). All contemporary 'GDMT-era' absolute benefit estimates are scenario-based modelling outputs. No randomized trial has evaluated ICDs on top of full modern GDMT in NICM; therefore, these results represent illustrative ranges rather than empirical estimates.