Activated partial thromboplastin time and clinical outcome after thrombin inhibition in unstable coronary artery disease

Aims Direct thrombin inhibitors have failed to prove superiority over unfra ctionated heparin in several clinical trials of unstable coronary artery di sease. We have investigated the relationship between activated partial thro mboplastin time levels and adverse clinical events, i.e. death, myocardial (re-)infarction or refractory angina. Methods and Results One thousand two hundred and nine patients with unstable coronary artery disease were random ized to 72 h infusion with inogatran, a low molecular mass direct thrombin inhibitor, or unfractionated heparin. During 30 days follow-up there was no significant difference between inogatran and unfractionated heparin treatm ent as regards clinical outcome. 11.6% of the 464 inogatran treated patient s with activated partial thromboplastin time above the median at 6 h (44 s) had a clinical event in 7 days, and 6.6% of the 423 patients with activate d partial thromboplastin time below the median (P=0.01). After 30 days the event rate was still 41% higher in the inogatran patients with activated pa rtial thromboplastin time above the median P=0.06). Activated partial throm boplastin time in quartiles indicated a direct relationship between higher activated partial thromboplastin time and worse outcome. In contrast, durin g heparin infusion there was a trend for improved clinical outcome with act ivated partial thromboplastin time above the median, but this benefit was l ost after cessation of treatment. Conclusions Higher activated partial thro mboplastin time levels during inogatran treatment are related to increased risk of death, myocardial infarction or refractory angina. This might, at l east in part, be explained by differences in anticoagulant mechanisms betwe en direct thrombin inhibitors and heparin, and further emphasizes the poorl y defined optimal activated partial thromboplastin time range during treatm ent with direct thrombin inhibitors in unstable coronary artery disease. (C ) 1999 The European Society of Cardiology.