Defining clinically relevant risk threshold for predicting sudden cardiac death

Defining clinically relevant risk threshold for predicting sudden cardiac death. Defining clinically relevant risk threshold for predicting sudden cardiac death Article Open access Published: 31 October 2026 Cite this article You have full access to this open access article Download PDF View saved research Defining clinically relevant risk threshold for predicting sudden cardiac death Download PDF Abstract 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.

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