Bivalirudin Decreases Bleeding Regardless of Heparin Anticoagulation Level

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Among patients undergoing percutaneous coronary intervention (PCI), use of bivalirudin during PCI was associated with lower bleeding rates compared with unfractionated heparin, with or without a glycoprotein IIb/IIIa inhibitor (GPI), according to a population-based study published online October 4, 2011, ahead of print in Circulation: Cardiovascular Interventions. This association was present regardless of the level of anticoagulation seen in the heparin group, with no increase in either in-hospital or 12-month ischemic outcomes, including stent thrombosis.

To assess the extent to which bivalirudin might affect bleeding rates, Sripal Bangalore, MD, MHA, of New York University School of Medicine (New York, NY), and colleagues analyzed data from the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) registry on 7,777 patients who underwent PCI between July 2004 and June 2007. The study population was split further into 3 groups:

• Heparin monotherapy (n = 1,767)
• Heparin plus GPI (n = 2,692)
• Bivalirudin (n = 3,318)

The heparin groups were then stratified into groups depending on the activating clotting time (ACT) achieved, with optimal ACT defined as 250-300 for heparin monotherapy and 200-250 when GPI was added.

Benefits Seen at All Clotting Times

In propensity-matched cohorts, bivalirudin therapy was associated with a 30% reduction in the primary endpoint of in-hospital composite bleeding compared with heparin monotherapy without a statistically significant increase in ischemic outcomes including stent thrombosis out to 1 year (table 1).

Table 1. Primary and Secondary Ischemic Outcomes

In addition, bivalirudin compared with heparin + GPI therapy was associated with a 57% reduction in the odds of composite bleeding, and no statistically significant increase in ischemic outcomes.

There were numerically lower bleeding rates at each level of achieved ACT compared with heparin monotherapy:

• Low: 2.5% vs. 4.7%; P = 0.21
• Medium: 1.9% vs 6.0%; P = 0.006
• High: 3.1% vs. 4.8%; P = 0.60

This was also true when comparing bivalirudin with heparin plus GPI:

• Low: 0.0% vs. 2.7%; P = 0.93
• Medium: 2.7% vs. 5.2%; P = 0.09
• High: 2.4% vs. 6.1%; P = 0.0003

Clinical Affirmation in Real-World Population

This study was designed to close the gaps in previous research on the ability of bivalirudin to lower bleeding risk compared to heparin, Bangalore told TCTMD in a telephone interview. He added that he expected positive results but was surprised at the benefits provided by bivalirudin across all arms.

“There have been increasing data to suggest that bivalirudin is helpful,” he said. “Based on these new data, I don’t think there is any doubt about the potency of bivalirudin at actually reducing the bleeding risk.”

Dr. Bangalore added that the study “reinforces the value of bivalirudin and at the same time reinforces the fact that there was no increase in ischemic events in a real-world population.”

In a telephone interview with TCTMD, Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), called the results a “welcome addition” to the bivalirudin vs. heparin conversation and said that the study, in conjunction with consistent past research, is clinically relevant.

“At least in the United States, there has been a movement toward increasing recognition of bleeding complications as being very important and I think physicians are recognizing over the years that bivalirudin is a good way to avoid bleeding complications,” he said. “So I think that clinically, this [study] should reaffirm that for many physicians.”

Further Anticoagulation Research

Although he generally agreed that the findings are clinically relevant, David F. Kong, MD, of Duke University Medical Center (Durham, NC), questioned the study’s measurement of ACT, in an e-mail communication with TCTMD.

“Overall, the paper reflects a reassuring trend that PCI is safe with lower-intensity anticoagulation,” he said. “[However], it is recognized that a numerically identical ACT on heparin and bivalirudin may actually reflect a different degree of anticoagulation, due to the differential effects of the drugs on clot-bound thrombin.”

Dr. Kirtane said that with physicians performing more and more transradial PCI, future research should focus on bivalirudin in that setting. Furthermore, he hypothesized that the bleeding reduction effects of the drug might not be as great when compared with transfemoral PCI. He said he would also like to see future studies assess the benefits of different anticoagulation regimens in patients treated with anti-platelet drugs like prasugrel and ticagrelor.

Source:

Bangalore S, Cohen DJ, Kleiman NS et al. Bleeding risk comparing targeted low-dose heparin with bivalirudin in patients undergoing percutaneous coronary intervention: Results from a propensity score-matched analysis of the Evaluation of Drug-Eluting Stent and Ischemic Events (EVENT) Registry. Circ Cardiovasc Interv. 2011;Epub ahead of print.

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