Weight-based unfractionated heparin dosing in STEMI patients resulted in only 33.8% achieving therapeutic initial aPTT, with markedly high aPTTs increasing bleeding risk (OR 2.11; P=0.004).
RCT (n=6,055)
randomized
Yes
What are the predictors and clinical consequences of nontherapeutic anticoagulation with weight-based unfractionated heparin in STEMI patients?
Despite using a standard weight-based nomogram, nontherapeutic anticoagulation with unfractionated heparin is frequent in STEMI patients, particularly in older, female, lower weight, and renal dysfunction patients, leading to increased bleeding or reinfarction risks.
BACKGROUND: Although weight-based nomograms have improved the efficacy and safety of dosing unfractionated heparin in ST-segment elevation myocardial infarction, achieving therapeutic anticoagulation in practice remains challenging. METHODS AND RESULTS: In the Enoxaparin and Thrombolysis in Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, 20 506 patients with ST-segment elevation myocardial infarction were randomized to enoxaparin or unfractionated heparin, the latter dosed according to the American College of Cardiology/American Heart Association weight-based nomogram with centrally monitored activated partial thromboplastin times (aPTTs). A total of 6055 patients received study unfractionated heparin and a fibrin-specific lytic and had an initial aPTT drawn within 4 to 8 hours of starting therapy. Despite close adherence to recommended dosing, only 33.8% of initial aPTTs were therapeutic (1.50 to 2.00 times control); 13.2% were markedly low ( or =2.75 times). Markedly high aPTTs were more likely in patients who were older (adjusted risk ratio RR(adj), 1.14 per decade; P=0.001), were female (RR(adj), 1.46; P<0.001), were of lower weight (RR(adj), 1.19 per 10-kg decrease; P<0.001) or had renal dysfunction (RR(adj), 1.08 per 0.2-mg/dL increase in serum creatinine; P=0.006). Markedly high aPTTs were associated with increased risk of TIMI major or minor bleeding by 48 hours (odds ratio, 2.11; P=0.004); markedly low aPTTs tended to be associated with increased risk of fatal or nonfatal reinfarction by 48 hours (odds ratio, 2.19; P=0.057). CONCLUSIONS: Despite the use of a standard weight-based unfractionated heparin nomogram in ST-segment elevation myocardial infarction, nontherapeutic anticoagulation is frequent and more likely among certain vulnerable patient groups, with excess anticoagulation associated with increased bleeding and inadequate anticoagulation associated with reinfarction. These findings should be considered when dosing unfractionated heparin in support of fibrinolytic therapy.
Cheng et al. (Tue,) conducted a rct in ST-segment elevation myocardial infarction (n=6,055). Unfractionated heparin vs. Enoxaparin was evaluated on Therapeutic initial aPTT (1.50 to 2.00 times control). Weight-based unfractionated heparin dosing in STEMI patients resulted in only 33.8% achieving therapeutic initial aPTT, with markedly high aPTTs increasing bleeding risk (OR 2.11; P=0.004).