To the Editor: We commend Dr Hulley and
colleagues1 on a well-designed, first-ever randomized trial
to evaluate continuous estrogen-progestin hormone replacement therapy
(HRT) for the secondary prevention of coronary heart disease (CHD).
Surprisingly and disturbingly, the results do not support the
beneficial effects of HRT found in observational studies.
Despite the appropriate randomization, blinding, and intention-to-treat
analysis, we are concerned that, during the trial, subjects in the
control and HRT groups were differently exposed to agents that could
affect the primary study outcomes. For example, the authors noted that
more women in the control group began treatment with lipid-lowering
agents (primarily statins) during the trial, and they astutely adjusted
for low-density lipoprotein levels during their analysis. However,
since statin use over an average of 5 years decreases coronary events
and coronary deaths in patients with CHD who have high and normal
cholesterol levels,2- 4 this differential utilization could
still bias the results toward not showing a difference between the 2
groups.