Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias

Abstract

Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

The effect of heparin infusion intensity on outcomes for bridging hospitalized patients with atrial fibrillation

“…17 Prior studies in the low to moderate risk AF population show increased bleeding events and similar thromboembolic events in those who received perioperative bridging compared to those who did not. [3][4][5][6][7] In 2017, an expert consensus recommended the use of parenteral anticoagulation for bridging patients with AF only in patients with a CHA 2 DS 2 -VASc score ≥5…”

“…However, prior studies were also unable to detect differences in thromboembolic events given the inherent low rate of occurrence in bridging and large numbers needed to show such a small difference. [3][4][5][6][7] The results of this study demonstrate that use of a low intensity UFH regimen in hospitalized AF patients can decrease major morbidity by decreasing both any and major bleeding event rates without a signal of increasing systemic thromboemboli. Low intensity UFH should now be the preferred dosing strategy for this population of patients in clinical practice.…”

“…A recent study demonstrated the risk of excess bleeding with higher initial UFH infusion rates in patients who received UFH for bridging in AF . The Roswell et al study demonstrated that the median initial UFH rate was higher in those who experienced bleeding events compared to those without bleeding events (13.3 units/kg/h vs 11.4 units/kg/h, P = .012) .…”

“…Published rates of bleeding in bridged patients are widely variable owing to different patient populations and different bridging methods. Of the studies reviewed, Roswell et al bore the most similar design, evaluating bleeding incidence for inpatient UFH bridging. The sample size for our study was based on the bleed rates published in Roswell et al which showed a 34% rate for any bleed and 9% rate for major bleeds for patients bridged with UFH infusion.…”

“…Studies have also shown that perioperative bridging in AF is associated with a 4-fold risk of bleeding compared to non-bridging strategies (any bleed rates: 5%-34% and major bleed rates: 3%-9%) with undifferentiated thromboembolic events (0%-4%). [3][4][5][6][7] Current guidelines and expert consensus support perioperative bridging with subcutaneous low molecular weight heparin or intravenous unfractionated heparin (UFH) for patients taking oral vitamin K antagonists who are at high risk for thromboembolism, indicated by a CHA 2 DS 2 -VASc score greater than 5 to 6 or a prior thromboembolic event. [8][9][10][11][12][13][14] However, there is currently limited data and differing consensus within guidelines and literature regarding UFH dosing intensity for bridging in AF.…”