ACUITY PCI: Bivalirudin Monotherapy is Effective
Benefits of monotherapy are driven by a nearly 50% reduction in bleeding events in ACS.
Among patients with moderate- and high-risk acute coronary syndromes undergoing percutaneous intervention, replacing heparin and GPIIb/IIIa inhibitors with bivalirudin alone improved overall event-free survival in the ACUITY PCI trial.
Gregg W. Stone, MD, Chairman of the Cardiovascular Research Foundation and Professor of Medicine at Columbia University Medical Center, presented the trial results on Tuesday.
“There were markedly reduced hemorrhagic complications, thereby improving overall event free survival,” Stone said.
Measured at 30 days, the adverse event rate was 11.7% for patients receiving bivalirudin monotherapy (Angiomax, The Medicines Company), significantly less than the rates for patients who received a combination of bivalirudin and a GPIIb/IIIa inhibitor, or a combination of heparin and a GPIIb/IIIa inhibitor (Figure 1).
This outcome was driven by a nearly 50% reduction in major bleeding. Bivalirudin monotherapy was associated with significant reductions in access site hematoma and several other bleeding endpoints (Figure 2).
Researchers noted no difference in the composite ischemia outcome. At 30 days, the ischemia-related adverse event rate was 8.9% in the bivalirudin monotherapy arm, 9.4% in the combination bivalirudin/GPIIb/IIIa inhibitor group, and 8.4% in the combination heparin/GPIIb/IIIa group.
Increase in MI
In a comment period following the presentation, Eric J. Topol, MD, the Chief Academic Officer and Director of Translational Sciences at the Scripps Research Institute in San Diego, Calif., suggested that there would be a trade-off between a reduction in major bleeding and an increase in MI with bivalirudin monotherapy.
“There is a trade off in a slight risk of MI,” Topol said.
Topol also pointed out a risk of early stent thrombosis that occured in 1.3% to 1.6% of patients despite potent antithrombotics.
The absolute MI rate at 30 days was 6.5% in the bivalirudin monotherapy group and 5.6% in the combination heparin GPIIb/IIIa therapy, a nonsignificant difference. Subgroup analyses found no impact from baseline troponin or the presence of baseline thienopyridine.
Nonrandomized trial
Stone said that the ACUITY PCI trial was limited because it was “not technically a randomized trial. The study design was open-label and, as such, bias cannot be excluded,” he said. “The ACUITY PCI trial was also underpowered for substudy evaluation, and therefore any subgroup analysis should be hypothesis generating.”
ACUITY PCI researchers enrolled 13,819 patients at 450 sites. Patients were randomized to one of three arms: combination heparin/GPIIb/IIIa (n = 4,603), combination bivalirudin/GPIIb/IIIa (n = 4,604) or bivalirudin alone (n = 4,612).
Angiography was performed within 72 hours, and then patients were further divided into medical management, PCI or CABG based on best management strategy. More than half (56.4%) of the patients underwent PCI, 32.2% were medically managed, and 11.4% underwent CABG.
Mean age of the patients was about 62 years, 73% were male. About 30% had diabetes and 65% had hypertension.
Drug-eluting stents were used in about 60% of patients.