Key Points:

• Trials measured bivalirudin vs. heparin-plus-protamine, bivalirudin vs. unfractionated heparin.

By TCT Daily Staff

Results from two European studies presented on Wednesday indicate that bivalirudin reduced bleeding rates compared with heparin, even in elective PCI.

One trial, ARNO, compared the efficacy of bivalirudin vs. heparin-plus-protamine in a setting that did not include routine use of abciximab. The other trial, NAPLES, examined the efficacy of bivalirudin vs. unfractionated heparin in patients
with diabetes.

ARNO trial

In the ARNO trial, patients undergoing elective PCI were assigned to one of two arms: 425 to bivalirudin alone and 425 to heparin plus the heparin-neutralizer protamine postprocedure.

All patients were pretreated with aspirin plus clopidogrel; abciximab was used on a provisional basis, more often in the heparin arm (27.6% vs. 14.6%, respectively; P=.0001).

Those who were assigned bivalirudin therapy had significantly lower in-hospital major bleeding rates (the primary endpoint) and a better net clinical outcome (death, MI, TVR, or major bleeding) at one month than those assigned unfractionated heparin-plus-protamine therapy, said David Antoniucci, MD, of the Careggi Hospital, in Florence, Italy.

 Major bleeding at one month also was significantly lower in the bivalirudin group, while minor bleeding was not different between the groups (see Figure 1).

The combined outcome of death, MI and TVR was significantly reduced in the bivalirudin group vs. the heparin group (2.8% vs. 6.4%, respectively; P=.014), although this was mainly driven by a reduction in overall death (0.2% vs. 1.4%, respectively; P=.057).

Net clinical outcome at 30 days demonstrated a highly significant difference between the groups, again favoring bivalirudin (3.3% vs. 8.0%, respectively; P=.004).

ISAR-REACT reversal

There was one acute and one subacute stent thrombosis in the bivalirudin group. No patients in the heparin arm developed acute stent thrombosis and there was one case of subacute stent thrombosis.

C. Michael Gibson, MD, of Brigham and Women’s Hospital in Boston, said that the results contrasted with the ISAR-REACT 3 study of 4,500 patients, which showed no significant difference between bivalirudin and heparin in either the triple endpoint of death, MI or urgent TVR, or net clinical outcome. Excess bleeding was reduced in the bivalirudin group in ISAR-REACT.

He also noted that the rate of bailout abciximab was higher than in other studies, which for bivalirudin "is usually around 7% compared to the 14% reported in the ARNO trial."

NAPLES trial

In the NAPLES trial, biomarker-negative patients with diabetes were randomized to two arms prior to elective PCI: 167 patients to bivalirudin alone and 168 to unfractionated heparin (UFH) plus tirofiban.

Carlo Briguori, MD, PhD, of the Clinica Mediterranea in Naples, Italy, reported bivalirudin monotherapy was found safe and feasible in that population. Bivalirudin resulted in a significant decrease of the composite endpoint of 30-day death, urgent revascularization, MI and bleeding. Monotherapy also was associated with a significant reduction in overall bleeding at 30 days (see Figure 2).

David F. Kong, MD, of Duke University Medical Center, in Durham, N.C., said that even though patients in NAPLES had diabetes, they were at low risk for ischemic events. "They had elective PCI, were biomarker negative, had 87% single-vessel intervention, and they uniformly received clopidogrel pre-treatment.

This is an exact mirror of the patient population that would have the least incremental benefit from GP IIb/IIIa blockade," he said.

"The principal benefit of GP IIb/IIIa inhibition is in high-risk populations. GP IIb/IIIa blockade increases the risk for major bleeding, so strategies to reduce bleeding complications are appropriate because the expected incidence of ischemic complications is low," Kong said.

Disclosures:

（source：www.tctmd.com）