January 1, 2008Circulation Journal2 citationsOpen Access

The Time Has Come for New, More Precise Guidelines in the Treatment of High-Risk Acute Coronary Syndromes With Heparin

ZMZuzana Moťovská PWPetr Widimský RPRobért Petr

Structured PICO

Does a weight-adjusted unfractionated heparin dosing regimen achieve optimal therapeutic aPTT levels in patients with high-risk NSTE ACS?

Population

267 consecutive patients with high-risk non-ST-segment elevation acute coronary syndrome (NSTE ACS) managed with an early (≤48h) invasive strategy. Mean age 70 years, 40% women. All patients were on dual antiplatelet therapy consisting of aspirin (100mg daily) and clopidogrel (initial loading dose 300mg and maintenance dose 75mg daily).

Intervention

Unfractionated heparin (UFH) administered via a weight-adjusted nomogram (bolus of 70 U/kg up to a maximum of 5,000 U, and an initial infusion of 12-15 U/kg/h up to a maximum of 1,000 U/h). Subsequent doses were adjusted after measurement of activated partial thromboplastin time (aPTT).

Outcome

Proportion of patients with a therapeutic initial aPTT value (1.5-2.5-fold of the control value) at 6 hours after starting therapy.surrogate

Weight-adjusted dosing of unfractionated heparin in high-risk NSTE ACS achieves early therapeutic aPTT in less than one-third of patients, highlighting the need for age- and sex-adjusted dosing guidelines.

Limitations

The study was not designed to evaluate clinical outcomes.

Abstract

BACKGROUND: The aim of this analysis was to define the risk factors associated with the problematic dose titration of unfractionated heparin (UFH) in high-risk non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients. METHODS AND RESULTS: The study group comprised 267 patients with high-risk NSTE ACS managed with an early invasive strategy and treated with the recommended dose of UFH. The subsequent dose was adjusted after measurement of activated partial thromboplastin time (aPTT), using the nomogram. The goal for aPTT was 1.5-2.5-fold of the control value. At 6 h after starting therapy 29% of patients had a therapeutic initial aPTT value; half of them were over-anticoagulated, and 22% were undertreated. By continuing therapy, the proportion of optimally treated patients increased; after 12 h of treatment 40% of patients reached the therapeutic dose, and 58% after 24 h. Undertreatment was a problem in < or = 65-year-old men. Women and older patients have a higher risk of overdose. The patients with a therapeutic dose of UFH had the lowest occurrence of major ischemic adverse events. CONCLUSIONS: Expert consensus on more precise dose guidelines for UFH is needed. The dose needs to be not only weight, but also age and sex, adjusted.

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