Practical implications of circadian variations in thrombolytic and antithrombotic activities

It recently has been demonstrated that thrombolytic therapy has circadian pattern of efficacy, as assessed by the ability to rapidly provide coronary patency. A study of 692 patients receiving intravenous tPA and undergoing acute coronary arteriography demonstrated a substantial diurnal pattern in patency with a peak at 8:00 pm. The heightened tendency for a coronary artery to be opened in the evening correlates well with the substantial tendency demonstrated in the same study and in multiple other studies for coronary arteries to thrombose and cause myocardial infarction in the morning hours. Circadian variations have been defined for a number of hemostatic and physiologic factors that would predispose toward clotting in the late morning, and converse circadian patterns have been described for a number of factors associated with thrombolysis that would predispose towards enhanced fibrinolysis in the evening hours. Methods by which efficacy of lytic therapy potentially could be enhanced include development of tPA variants or adjunctive agents that eliminate the circadian nadirs of efficacy, modification of dosage or choice of lytic agent as a function of time of treatment, and selection between pharmacologic lysis and direct angioplasty as a function of time of day.