Determinants of the Response to Coumarin Anticoagulants in Patients With Acute Myocardial Infarction

Determinants of the response to coumarin anticoagulant, warfarin, have been analysed in a series of 19 patients with acute myocardial infarction. Cardiac failure developing in the acute phase of the disease seemed to be without any great influence on the plasma half‐life of warfarin, with the exception of patients in whom serious circulatory catastrophes occurred. In patients who had received other drugs regularly before the hospital admission the plasma half‐life of warfarin showed a significant prolongation within 3 weeks—a phenomenon apparently caused by a decreasing induction of microsomal drug‐metabolizing enzymes in the liver. The plasma half‐life of warfarin was found to explain 44% of the variance in the daily requirement of warfarin during maintenance treatment. The steady state “therapeutic” plasma warfarin level showed a wide range of individual variation—from 0.8 to 4.1 mg/l, with a median value of 1.5 mg/l. The results indicate that in addition to the rate of coumarin anticoagulant metabolism other factors have a marked influence on the response to coumarin drugs in patients with myocardial infarction.