THROMBIN INHIBITION WITH INOGATRAN FOR UNSTABLE ANGINA-PECTORIS - EVIDENCE FOR REACTIVATED ISCHEMIA AFTER CESSATION OF SHORT-TERM TREATMENT

Background The acute coronary syndromes of unstable angina and non-Q-w ave infarction are initiated by coronary plaque rupture and subsequent thrombus formation, Thrombin is central to this response as it activa tes platelets and the coagulation system. In an open design study we a ssessed the tolerability and safety of the low molecular weight thromb in inhibitor, inogatran, for unstable angina or non-Q-wave infarction. Methods Thirty-seven patients, treated within 72 h of symptoms, were allocated consecutively to groups to receive a 4 h infusion with one o f three doses of inogatran. Thrombin generation and activity were meas ured with plasma markers at baseline, after the 4 h treatment period a nd 4 h later. Ischaemia was monitored using continuous vectorcardiogra phy during the 4 h of treatment and during the subsequent 4 h after in ogatran infusion had been stopped, to detect any increase in ischaemic events after the period of treatment, In addition, 12 patients receiv ed inogatran as an infusion for 72 h. Results Inogatran was tolerated well. There were no adverse haemodynamic effects or allergic reactions , Minor bleeding events were detected in 37% of the patients. The bioc hemical and vectorcardiographic findings indicated suppression of thro mbin generation after the 4 h treatment period compared with baseline, During the first 4 h after inogatran treatment, thrombin activity and episodes of ischaemia were increased compared with during the treatme nt period. Conclusion Inogatran was tolerated well and was safe, but i ts discontinuation was followed by a reactivation of thrombin activity and ischaemia. Whether this reactivation represented a rebound phenom enon, or merely resulted from the discontinuation of an effective ther apy, cannot be established from the present study.