Exposing patients with chronic, stable, exertional angina to placebo periods in drug trials.
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.
Glasser
S P
SP
University of South Florida, College of Medicine, Tampa 33612.
Clark
P I
PI
Lipicky
R J
RJ
Hubbard
J M
JM
Yusuf
S
S
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000787:Angina Pectoris / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications; D002908:Chronic Disease; D004311:Double-Blind Method; D015507:Drugs, Investigational / Q000627:therapeutic use; D004992:Ethics, Medical; D006801:Humans; D005082:Physical Exertion; D010919:Placebos; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D015507:Drugs, Investigational; D010919:Placebos