Key result
Implantable cardioverter-defibrillator therapy reduced overall mortality by 18% (HR 0.82, 95% CI 0.77-0.90) in pooled RCTs, requiring a >=3% annual sudden cardiac death risk to achieve an NNT <=20.
Why the study?
There is no consensus on a sudden cardiac death (SCD) risk threshold for designing and evaluating prediction models and guiding implantable cardioverter-defibrillator (ICD) therapy decisions.
Does implantable cardioverter-defibrillator (ICD) therapy achieve a clinically relevant reduction in overall mortality (NNT <= 20) at a definable minimum annual sudden cardiac death risk threshold when accounting for competing non-sudden mortality?
Meta-Analysis (n=12,321)
Yes
Does implantable cardioverter-defibrillator (ICD) therapy achieve a clinically relevant reduction in overall mortality (NNT <= 20) at a definable minimum annual sudden cardiac death risk threshold when accounting for competing non-sudden mortality?
Establishes a pragmatic population-level benchmark of >=3% annual sudden cardiac death risk (or >=1.3% over 10 years in low competing-risk populations) required for primary-prevention ICD therapy to yield a clinically meaningful mortality benefit (NNT <= 20).
Supports ICD use at >=3% annual SCD risk for NNT<=20; extends prior RCTs by quantifying competing-mortality thresholds for meaningful benefit.
There is no consensus on a risk threshold for sudden cardiac death (SCD) that could be used in practical design and evaluation of prediction models and decisions regarding implantable cardioverter-defibrillator (ICD) therapy. Baseline assumptions for a simulation framework were derived from previous randomized controlled trials ( n = 18) to identify minimal average SCD risk threshold that would translate to mortality benefit by ICD therapy also considering the effect of competing non-sudden mortality. ICD efficacy to prevent SCDs and other data for simulations were estimated using inverse-variance weighted meta-analysis of included trials. Number needed to treat (NNT) was evaluated over a 5- and 10-year horizons (≤ 20 defined as clinically relevant). Correlation analysis confirmed average annual SCD incidence in trial populations as the key factor associating with ICD therapy effectiveness to reduce mortality (Pearson’s r = 0.653, p < 0.01). In a simulation assuming 5% annual non-sudden mortality (pooled estimate of included RCTs) and a 56% (48–62%) efficacy for ICDs to reduce SCDs or similar events, 3% average annual SCD risk (≈ 12% over 5 years) emerged as the lowest practical threshold even after controlling for excess (overlapping) mortality among those saved successfully from SCD by ICD therapy. In populations with very low incidence of non-sudden mortality (1%), the lowest practical threshold over a longer 10-year time horizon was 1.3% (assuming no overlapping mortality). Even under substantial competing risk, populations with an average 3% (or higher) annual SCD incidence most likely would benefit from ICD therapy. Lower threshold may be considered only in populations with very low non-sudden mortality.
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Hernesniemi et al. (2026) conducted a meta-analysis in Sudden cardiac death risk (primary and secondary prevention populations) (n=12,321). Implantable cardioverter-defibrillator (ICD) therapy vs. Control populations not initially randomized to ICD therapy was evaluated on Overall mortality reduction by ICD therapy (meta-analysis) and minimum annual SCD risk threshold to achieve NNT <= 20 over 5 years (simulation) (HR 0.82, 95% CI 0.77-0.90, p=<1x10^-5). Implantable cardioverter-defibrillator therapy reduced overall mortality by 18% (HR 0.82, 95% CI 0.77-0.90) in pooled RCTs, requiring a >=3% annual sudden cardiac death risk to achieve an NNT <=20.
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