The effect of aspirin on the circadian pattern of myocardial infarction is also uncertain. In the TIMI Phase II and the International Study of Infarct Survival (ISIS) 2 patient populations, a history of aspirin use or nonuse at the time of infarction did not affect the morning increase in infarction incidence (27,35). In contrast, the Physician's Health Study followed 22,071 healthy middle-aged men randomized to aspirin or placebo over 5 yr (169). The aspirin group had a 44.8% reduction in the incidence of nonfatal infarction, with an additional 25.2% reduction between 4 am and 10 am (Fig. 15). One other study of consecutive myocardial infarction admissions reported a beneficial effect of aspirin similar to that in the Physician's Health Study (69). The Myocardial Infarction Onset Study also found that regular users of aspirin had a reduction in the relative risk of myocardial infarction induced by episodes of anger (103).
The efficacy of thrombolytic agents also appears to have a circadian variation. In one study of 692 patients undergoing coronary arteriography 90 min after receiving intravenous tissue-type plasminogen activator, complete patency was observed in 42% of patients given the drug between noon and midnight, compared to 29% of patients given the drug between midnight and noon (p < 0.001) (170). Two smaller studies demonstrated similar effects (171,172).
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