Diagnostic heterogeneity in clinical trials for congestive heart failure.

There are no uniform diagnostic criteria for congestive heart failure. To determine the pattern of diagnostic criteria used, reports of 51 randomized, double-blind, placebo-controlled, clinical drug trials published between 1977 and 1985 were reviewed. Only 23 (45%) of the trials specified objective diagnostic criteria beyond treatment history, clinical diagnosis, or functional class. Of these, there were two trials each for digoxin, hydralazine, amrinone, and metoprolol; for each pair, only one study showed therapy beneficial. Of the amrinone pair, the positive study required a lower ejection fraction (less than 30% compared with less than 45%) and selected patients with more clinical severity. Conversely, for metoprolol, the positive study specified a higher ejection fraction (less than 49% compared with less than 35%) and selected patients with clinically milder disease, suggesting that conflicting results may relate to differences in study population. Many studies of congestive heart failure are done without explicit diagnostic criteria. Criteria lack uniformity, and such discrepancies may explain conflicting results.