Exposing patients with chronic, stable, exertional angina to placebo periods in drug trials
S. P. Glasser, P. I. Clark, R. J. Lipicky, J. M. Hubbard and S. Yusuf
University of South Florida, College of Medicine, Tampa 33612.
Because the safety of withholding standard therapy and enrolling patients
with stable angina in placebo-controlled trials is not known, we identified
all events leading to dropout from trials of 12 antianginal drugs submitted
in support of new drug applications to the US Food and Drug Administration.
Persons who dropped out of the trials were classified as cause due to
adverse cardiovascular events or other causes without knowledge of drug
assignment. There were 3161 subjects who entered any randomized,
double-blind phase of placebo-controlled protocols; 197 (6.2%) withdrew
because of cardiovascular events. There was no difference in risk of
adverse events between drug and placebo groups. A prospectively defined
subgroup analysis showed that groups who received calcium antagonists were
at an increased risk of dropout compared with placebo groups (P = .04),
primarily because of a disproportionate number of adverse events in studies
of one drug. In conclusion, there were few adverse experiences associated
with short-term placebo use. Withholding active treatment does not increase
the risk of serious cardiac events.
