Higher Maximum Doses and Infusion Rates Compared with Standard Unfractionated Heparin Therapy Are Associated with Adequate Anticoagulation without Increased Bleeding in Both Obese and Nonobese Patients with Cardiovascular Indications.

Abstract

To evaluate the time to achieve therapeutic activated partial thromboplastin time (aPTT) values and occurrence of bleeding based on standard unfractionated heparin (UFH) weight-based dosing recommendations compared with an aggressive weight-based UFH dosing strategy using higher maximum doses and infusion rates in both obese and nonobese patients who presented with non-ST-segment elevation myocardial infarction or unstable angina (NSTEMI/UA) or atrial fibrillation. Retrospective cohort study. Academic medical center. A total of 197 adults were included who were admitted for NSTEMI/UA, atrial fibrillation, or other cardiac indications and received at least 6 hours of a continuous UFH infusion. Of those patients, 71 were treated with standard UFH dosing (60-unit/kg bolus [or maximum 4000 units] followed by an infusion of 12 units/kg/hour [or maximum 1000 units/hr]) between September 2013 and February 2014, and 126 patients received an aggressive UFH dosing strategy (60-unit/kg bolus [or maximum 10,000 units] followed by an infusion of 12 units/kg/hr [or maximum 2250 units/hr]) between October 2014 and March 2015. Patients in the standard dosing and aggressive strategy cohorts were further classified by body mass index status (normal, overweight, obese, and morbidly obese) and weight status. A time-to-event analysis for achievement of therapeutic aPTT range (60-80 sec) was assessed. A significantly higher proportion of patients treated with the aggressive strategy achieved a therapeutic aPTT within 6 hours (23% vs 11%, p=0.043). The delay or failure to achieve therapeutic anticoagulation was particularly evident in obese patients in the standard dosing group. The mean ± SD initial infusion rate was 10.8 ± 1.4 units/kg/hour in the standard dosing group versus 12 ± 0.02 units/kg/hour in the aggressive strategy group (p=<0.0005). The occurrence of supratherapeutic aPTT values and the highest aPTT achieved were similar between the two dosing groups (p=0.817 and p=0.348, respectively). No bleeding events were reported in either group. Patients who had higher UFH maximum bolus doses and infusion rates achieved therapeutic anticoagulation more rapidly, without increased bleeding, and these doses can be adjusted for obese as well as nonobese patients. However, despite use of the higher doses, only 23% of patients achieved therapeutic aPTT values within 6 hours, suggesting that an even higher bolus dose and infusion rate may still be warranted.