RELATION BETWEEN SYSTEMIC ANTICOAGULATION AS DETERMINED BY ACTIVATED PARTIAL THROMBOPLASTIN TIME AND HEPARIN MEASUREMENTS AND IN-HOSPITAL CLINICAL EVENTS IN UNSTABLE ANGINA AND NON-Q-WAVE MYOCARDIAL-INFARCTION

Although coronary thrombosis is thought to play a pivotal role in the pathogenesis of unstable angina and non-Q wave myocardial infarction a nd antithrombotic therapy is a mainstay in the early management of the se patients, the relation between measures of systemic anticoagulation and clinical events has not been defined clearly. In the Thrombolysis in Myocardial Ischemia III trial, 1473 patients with ischemic chest p ain at rest evaluated within 24 hours of symptom onset were randomized to (1) tissue plasminogen activator (TPA) or placebo and (2) an early invasive or an early conservative strategy. All patients received a f ull complement of antiischemic medication, aspirin, and continuous int ravenous heparin titrated to an activated partial thromboplastin time (aPTT) of 1.5 to 2.0 times control for 72 to 96 hours. The median aPTT in all study groups exceeded the minimum threshold (45 seconds) by 24 hours and remained within the designated range during the protocol-di rected heparin infusion. No differences in median aPTT values for the 72- to 96-hour study period were observed between groups (p = not sign ificant). Median 12-hour heparin concentrations were >0.2 U/ml in all groups; however, values <0.2 U/ml were common thereafter, particularly in TPA-treated patients. Time-dependent covariate analyses failed to identify statistically significant differences in either aPTT or hepar in levels between patients with in-hospital clinical events (spontaneo us ischemia, myocardial infarction, or death) and those without events (p = 0.27). Furthermore, early clinical events occurred in a similar percentage of patients with optimal anticoagulation (all aPTTs >60 sec onds, all heparin levels >0.2 U/ml), and those with aPTTs or heparin l evels below these thresholds. Aggressive (high-intensity) anticoagulat ion with heparin to achieve aPTTs >2.0 times control does not appear t o offer additional clinical benefit to lower levels (1.5 to 2.0 times control) among patients with unstable angina and non-Q wave myocardial infarction receiving intravenous heparin and oral aspirin. Therefore, the optimal level of anticoagulation in this common clinical setting is between 45 and 60 seconds when heparin is included in the treatment strategy. Direct plasma heparin measurement does not offer an advanta ge to routine aPTT monitoring. The occurrence of spontaneous ischemia, myocardial infarction, and death in spite of antiischemic therapy and optimal anticoagulation (as it is currently defined) with heparin sup ports ongoing efforts to develop more effective antithrombotic agents.