K. Andersen et al., THROMBIN INHIBITION WITH INOGATRAN FOR UNSTABLE ANGINA-PECTORIS - EVIDENCE FOR REACTIVATED ISCHEMIA AFTER CESSATION OF SHORT-TERM TREATMENT, Coronary artery disease, 7(9), 1996, pp. 673-681
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.