Bleeding Risk Comparing Targeted Low-Dose Heparin With Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention

Abstract

Background— Prior randomized trials have shown reduced bleeding with bivalirudin compared with unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI). However, it is not known if this benefit is also present when UFH doses are more tightly controlled (as measured by activated clotting time, ACT). Methods and Results— Patients enrolled in the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) registry, were divided into 3 groups, based on the antithrombotic drug used during PCI (UFH monotherapy, UFH+glycoprotein IIb-IIIa receptor inhibitor [GPI], or bivalirudin alone). Propensity score matching was used to adjust for measured covariates (89 variables) and to compare bivalirudin versus UFH monotherapy and bivalirudin versus UFH+GPI groups. The UFH groups were stratified based on ACT achieved (optimal ACT defined as 250–300 for UFH monotherapy and 200–250 when GPI was also used). The primary bleeding outcome was in-hospital composite bleeding, defined as events of access site bleeding, Thrombolysis In Myocardial Infarction major/minor bleeding, or transfusion. Primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/MI/unplanned repeat revascularization at 12 months) were also evaluated. Propensity score matching yielded 3022 patients for the UFH monotherapy versus bivalirudin comparison and 3520 patients for the UFH+GPI versus bivalirudin comparison. Bivalirudin use was associated with numerically lower bleeding rates at all categories of achieved ACT when compared with UFH (low, optimal, high ACT: 2.5% versus 4.7%, 1.9% versus 6.0%, 3.1% versus 4.8%, respectively) or heparin+GPI groups (low, optimal, high ACT: 0.0% versus 2.7%, 2.7% versus 5.2%, 2.4% versus 6.1%, respectively) and was not associated with any statistically significant increase in either primary or secondary ischemic outcomes. Conclusions— Among unselected patients undergoing PCI, bivalirudin use during PCI was associated with a lower risk of bleeding at all comparator ACT levels without an increase in ischemic outcomes.

Heparin Monotherapy or Bivalirudin During Percutaneous Coronary Intervention in Patients With Non–ST-Segment–Elevation Acute Coronary Syndromes or Stable Ischemic Heart Disease

“…In our previous study from EVENT, we have shown that use of bivalirudin use during PCI was associated with a lower risk of bleeding at all comparator-activated clotting time levels without an increase in ischemic outcomes demonstrating the efficacy of bivalirudin at reducing bleeding even when compared with low dose of UFH. 18 Taken together with the current study, there are thus consistent data suggesting reduced bleeding with bivalirudin in patients with STEMI, NSTEACSs, or SIHD and when compared with UFH+GPI or UFH monotherapy and across various comparator activated clotting time levels. The association between bivalirudin and ischemic outcomes, however, needed to be explored in larger trials.…”

Comparison of Bivalirudin and Radial Access Across a Spectrum of Preprocedural Risk of Bleeding in Percutaneous Coronary Intervention

“…The impact of bivalirudin on the incidence of periprocedural bleeding has been also evaluated in clinical trials (6, 18–23) and registries (3, 24–25), consistently demonstrating lower bleeding risk in all studied clinical scenarios. Adding vascular closure devices to bivalirudin in the setting femoral access is associated with even better safety.…”

A Historical Perspective on the Reversal of Anticoagulants

“…It has a lower risk of MBE compared with heparin-based regimens. 129 130 There is no specific reversal agent approved for bivalirudin. Idarucizumab is ineffective for bivalirudin reversal.…”