We attempted to replicate the approach of the WHI
investigators where possible, carrying out prespecified
analyses looking for interactions between
pre-specified subgroups based on use (no use v any
use) and dose (0, 1–499, 500–999, ≥1000 mg/day) of
personal calcium supplements at randomisation for
cardiovascular events. We pre-specified assessment
of four cardiovascular end points and their combinations:
myocardial infarction, coronary revascularisation
(coronary artery bypass grafting or percutaneous
coronary intervention), death from coronary heart disease,
and stroke. Serial electrocardiograms were carried
out in the WHI CaD Study, allowing detection
of silent myocardial infarctions. Because silent myocardial
infarctions were not determined in any of the
trials in our meta-analysis, we analysed data separately
for clinical myocardial infarctions and total myocardial
infarctions (including clinical and silent myocardial
infarction).We have reported four different composite
end points: total deaths from myocardial infarction or
coronary heart disease (the major outcome reported in
theWHICaD Study); clinical myocardial infarction or
coronary revascularisation (representing clinical coronary
heart disease events); clinical myocardial infarction
or stroke (the composite end point most similar to
that used in our meta-analysis of calcium monotherapy
trials); and total myocardial infarction, coronary revascularisation,
and death from coronary heart disease
(representing all coronary heart disease events).