WASHINGTON — The direct thrombin inhibitor bivalirudin seems to be more effective than heparin in reducing major bleeding episodes in patients undergoing percutaneous coronary intervention, according to a study presented at a symposium sponsored by the Cardiovascular Research Foundation.
The study, ACUITY-PCI, is a substudy of the Acute Catheterization and Urgent Intervention Triage Strategy trial. ACUITY was presented at the American College of Cardiology meeting in March; the ACUITY-PCI results were presented at a symposium sponsored by the Cardiovascular Research Foundation (CRF).
In ACUITY-PCI, 7,789 patients who underwent catheterization were randomized to one of three arms: unfractionated heparin or enoxaparin (Lovenox), depending on local hospital practice, combined with a glycoprotein IIb/IIIa inhibitor; bivalirudin (Angiomax) with a glycoprotein IIb/IIIa inhibitor; or bivalirudin alone. These were high-risk patients: 65% in each arm—about 1,690 patients in each group—had elevated troponin levels at baseline. Patients underwent PCI within 20 hours of admission. There was a mean of 1.5 lesions attempted per patient.
The majority of patients in each arm had a stent implanted, with 60% getting a drug-eluting stent, said Dr. Gregg Stone, CRF vice-chairman and a professor of medicine at Columbia University, New York.
The study measured three primary end points at 30 days postcatheterization: a composite net clinical benefit, an ischemic composite, and major bleeding. Major bleeding was defined as noncoronary artery bypass-related bleeding, intracranial hemorrhage, intraocular bleeding, retroperitoneal bleeding, reoperation for bleeding, and major transfusion.
Overall, bivalirudin alone reduced major bleeding by 48%. There was a 50% reduction in the need for transfusions, said Dr. Stone.
At 30 days, 7% of patients in the heparin plus glycoprotein IIb/IIIa inhibitor, 8% of patients receiving bivalirudin plus a glycoprotein IIb/IIIa inhibitor, and 4% of patients receiving bivalirudin alone had major non- coronary artery bypass graft bleeding.
There was no difference among the three arms in the components of the composite end point of ischemia: death, myocardial infraction, or unplanned revascularization for ischemia, said Dr. Stone.
In addition, there was no difference among the arms in patients who had elevated troponin levels in net clinical outcomes, ischemic composite, or major bleeding.
The study authors also examined patients who had exposure to a thienopyridine—usually clopidogrel (Plavix). Again, there was a major reduction in bleeding with bivalirudin alone, whether patients had taken a thienopyridine or not, said Dr. Harvey White, of Green Lane Hospital in Auckland, New Zealand, who briefed reporters on the results.
The study authors concluded that in patients with moderate and high-risk acute coronary syndrome undergoing contemporary PCI, replacing the standard of heparin and a glycoprotein IIb/IIIa inhibitor with bivalirudin alone results in similar rates of ischemia and a 50% reduction in bleeding, said Dr. White.
The study also helped assuage concerns about using bivalirudin in troponin-positive patients.
And, he added, the findings are consistent with the results seen in Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2), in which there was a 41% reduction in major bleeding with bivalirudin alone.
Dr. Stone noted that ACUITY-PCI did have some limitations, including that it is not technically a randomized trial and that it was underpowered for noninferiority testing and subgroup analysis. It should be considered a hypothesis-generating study, he said.
In discussing the ACUITY-PCI, Dr. Eric Topol, chairman of the department of cardiovascular medicine at Case Western Reserve University, Cleveland, said that the subgroups were still interesting to examine, especially the impressive results in patients with troponin elevations.
One interesting note—despite large amounts of antiplatelet therapy, there was still a stent thrombosis rate of about 1.4% at 30 days, said Dr. Topol.
Overall, “There is a trade-off with a slight increase in MI, which is small, but it's compared with a significant, greater than 50% reduction in bleeding,” said Dr. Topol.
He also agreed that the replication of the REPLACE-2 results give “key validation” to bivalirudin's utility.
Dr. Topol had no conflicts to report. Dr. White served briefly as a consultant to the Medicines Company, which makes bivalirudin. Dr. Stone is on the speaker's bureau for the Medicines Company and also receives significant research support.
Bivalirudin alone reduced major bleeding by 48% and cut the need for transfusions by 50%. DR. STONE