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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. Thrombolysis in Myocardial Ischemia III B In

Abstract：

:Although coronary thrombosis is thought to play a pivotal role in the pathogenesis of unstable angina and non-Q wave myocardial infarction and antithrombotic therapy is a mainstay in the early management of these 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 pain 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 full complement of anti-ischemic medication, aspirin, and continuous intravenous 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-directed heparin infusion. No differences in median aPTT values for the 72- to 96-hour study period were observed between groups (p=not significant). 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 heparin levels between patients with in-hospital clinical events (spontaneous 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 seconds, all heparin levels>0.2 U/ml), and those with aPTTs or heparin levels below these thresholds. Aggressive (high-intensity) anticoagulation with heparin to achieve aPTTs >2.0 times control does not appear to 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 advantage to routine aPTT monitoring. The occurrence of spontaneous ischemia, myocardial infarction, and death in spite of antischemic therapy and optimal anticoagulation (as it is currently defined) with heparin supports ongoing efforts to develop more effective antithrombotic agents.

journal_name

Am Heart J

journal_title

American heart journal

authors

Becker RC,Cannon CP,Tracy RP,Thompson B,Bovill EG,Desvigne-Nickens P,Randall AM,Knatternud G,Braunwald E

doi

10.1016/s0002-8703(96)90519-0

subject

Has Abstract

pub_date

1996-03-01 00:00:00

pages

421-33

issue

eissn

0002-8703

issn

1097-6744

pii

S0002-8703(96)90519-0

journal_volume

131

pub_type

临床试验,杂志文章,多中心研究,随机对照试验,评审

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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. Thrombolysis in Myocardial Ischemia III B In