WASHINGTON – The antithrombotic agent bivalirudin has a safety profile similar to that of unfractionated heparin for prevention of thrombotic events during percutaneous coronary intervention for an acute coronary syndrome, according to a small, prospective, multicenter trial.
SWITCH III (Switching From Fondaparinux to Bivalirudin or Unfractionated Heparin in ACS Patients Undergoing PCI) is the third in a series of trials looking at anticoagulation combinations in PCI patients.
Dr. Ron Waksman
Treatment of ACS patients with fondaparinux followed by early angiography, then appropriate medical, PCI, or coronary artery bypass graft management is safe and effective, according to lead investigator Dr. Ron Waksman. He cited the OASIS 5 study, which showed the superiority of fondaparinux, a factor Xa inhibitor, over the low-molecular-weight heparin enoxaparin for patients presenting with acute coronary syndrome (N. Engl. J. Med. 2006;354:1464-76).
However, the increase in thrombus within the catheter among patients undergoing PCI suggested that additional anticoagulation during PCI was needed for patients on fondaparinux, he added.
The main objective of the trial was to evaluate the safety of switching from fondaparinux (Arixtra) to either unfractionated heparin or bivalirudin (Angiomax) for patients with acute coronary syndrome undergoing percutaneous coronary angioplasty, said Dr. Waksman, director of experimental angioplasty and emerging technologies for the Cardiovascular Research Institute at MedStar Washington (D.C.) Hospital Center.*
A total of 100 adult patients from six centers in the United States and Canada were enrolled in the study. They presented with ACS, unstable angina, or non–ST-elevated myocardial infarction, and had been treated with fondaparinux within the previous 24 hours. All were eligible for PCI, and required PCI of at least one artery. Their target lesion stenosis was less than 100%.
The primary end point of the study was clinically overt, in-hospital major bleeds. These included fatal bleeds, intracranial hemorrhage, retroperitoneal hemorrhage, and bleeds requiring transfusion of two or more units of RBCs or equivalent whole blood.
The secondary end point was in-hospital death (nonhemorrhagic), vascular access site complications, MI, need for repeat revascularization, procedural complication, and catheter thrombosis.
All patients received fondaparinux (2.5 mg) prior to coronary angiography. They were then randomized to receive bivalirudin (51 patients) or unfractionated heparin (49 patients) during coronary angiography, and were followed through during their hospital stay.
For intraprocedural anticoagulation, three of the patients in bivalirudin group received unfractionated heparin, while one patient in the heparin group received bivalirudin. None of the patients were given low-molecular-weight heparin or lytic therapy.
Radial access was the more common angiographic route, used in 35 of the bivalirudin group and 33 of the heparin group, an indication of the growing use of that approach, Dr. Waksman said.
The average percentage of diameter stenosis was 80.5 in bivalirudin group and 78.6 in the heparin group. The procedure length was similar in both groups.
Regarding the primary outcome, no deaths or fatal bleeding occurred in either group. However, one of the patients in the bivalirudin group experienced major bleeding.
The secondary, efficacy end points were similar between groups for the most part. There was no catheter thrombosis, myocardial infarction, or stent thrombosis in either arm. However, there was 2% repeat revascularization in the heparin group, compared with none in the bivalirudin group. Access site complications, on the other hand, were more common in the bivalirudin group, at 5.9%, compared with 2% with fractionated heparin.
"Lack of intracatheter thrombus in the bivalirudin group suggests that it can be used safely in ACS patients initially treated with upstream fondaparinux," said Dr. Waksman.
Dr. Gregg W. Stone, who commented on the study at the meeting, called the findings "interesting and thought provoking." However, "I don’t think it will have much of an impact in the United States, because going through something like fondaparinux or low-molecular-weight heparin for days before going to the cath lab could just lead to an increase in adverse outcomes during the waiting period," said Dr. Stone, director of cardiovascular research and education at New York–Presbyterian Hospital and professor of medicine at Columbia University, New York.
The study had two major limitations. It included only a small number of patients and "it is not powered to detect intergroup differences," said Dr. Waksman. In addition, nearly two-thirds of the patients were treated via the radial artery, which may have minimized bleeding at the access site, he added.
Dr. Waksman added that larger randomized trials are needed to establish the safety and efficacy of bivalirudin in clinical settings.
SWITCH III was sponsored by MedStar Washington Hospital Center* and GlaxoSmithKline, which makes fondaparinux. Dr. Waksman has received honoraria from Abbott Laboratories, Boston Scientific, and Merck, and consulting fees from Medtronic. Dr. Stone has received consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company (maker of bivalirudin), Daiichi Sankyo, and Eli Lilly.