Time as a factor in thrombolytic therapy

Animal studies first demonstrated the importance of early reperfusion in limiting the size of eventual infarction. This has been confirmed by human studies in which the early patency of the infarct-related artery is correlated with prognosis. Large randomised clinical trials suggested a graded effect, with a particularly great benefit if therapy was administered during the first hour after the onset of symptoms, and a progressive diminution in the effect thereafter, up to 12 h, and perhaps beyond. These studies did not, however, randomise patients to earlier or later treatment so the comparisons of different time intervals were not entirely valid. Five mortality trials have now randomised patients to early or later treatment and have demonstrated a significant benefit if more than 1 h is gained thereby. These trials were individually not large enough to establish the degree of gain from earlier treatment, but pooling their results suggests that gaining about 1 h will reduce mortality by about 17%.