Simulation of a putative susceptibility risk factor to explain the findings of the Heart and Estrogen/progestin Replacement Study (HERS)

In the HERS trial, hormone therapy did not reduce the risk of coronary events. In post hoc analyses, treatment was associated with early harm and late benefit. According to one hypothesis, a risk factor may well distinguish a susceptible subgroup with early events associated with hormone therapy from a nonsusceptible subgroup who benefit from hormone therapy. In simulation studies, it appeared that only a susceptibility factor with a low prevalence (3–5%) and a high risk ratio (13–25‐fold) can produce the pattern of risks seen in HERS. The number of candidate factors is likely to be small.