WASHINGTON — A prolonged infusion of bivalirudin during complex or multivessel percutaneous coronary interventions produced a significantly lower rate of procedure-related myocardial infarctions than did an intraprocedural infusion alone, without increasing the rate of major bleeding, in a small randomized trial of 178 patients with stable or unstable angina.
Previous studies have reported slightly higher rates of myocardial infarction or acute stent thrombosis in patients treated with bivalirudin, compared with patients who received heparin and a glycoprotein IIb/IIIa inhibitor, especially when there is an inadequate level of platelet inhibition provided by thienopyridines before the procedure, according to Dr. Bernardo Cortese of the department of interventional cardiology at the Ospedale della Misericordia, Grosseto, Italy.
In the PROBI VIRI study (Prolonged Bivalirudin Infusion Versus Intraprocedural Only Randomized Study), Dr. Cortese and his colleagues sought to determine if a prolonged infusion of bivalirudin for 4 hours after PCI (at 0.25 mg/kg per hour) could lower the rates of these events.
“We think that a prolonged infusion of bivalirudin in a specific subset of patients could be a reasonable choice to treat these patients with complex PCI and possibly emergent or urgent PCI to prevent stent thrombosis,” Dr. Cortese said at Transcatheter Cardiovascular Therapeutics 2008. Dr. Cortese is a consultant to Medicines Co., which manufactures bivalirudin.
To be randomized in the trial, patients were required to have stable or unstable angina and at least one complex lesion or a planned multivessel PCI.
The enrolled patients had a mean age of about 67 years; 40% had unstable angina, and 80% had a complex coronary lesion.
Procedure-related MIs occurred significantly less often in patients who received prolonged bivalirudin than in those who received bivalirudin only during the procedure (6.8% and 16.7%, respectively). These MIs were defined by a rise in the level of CK-MB (the MB isoenzyme of creatine kinase) to three or more times the upper limit of normal.
Patients on prolonged bivalirudin achieved lower, yet statistically similar, rates of major adverse cardiac events at 30 days and 6 months (1.1% and 10.2%, respectively) than did patients who received bivalirudin only during the procedure (3.3% and 16.7%, respectively). Each group experienced similar rates of in-hospital bleeding described as major (about 1%) or minor (about 3%). No cases of stent thrombosis occurred.
The results raise the issue of “what should we do with stent thrombosis? Is it longer bivalirudin? Or is it more potent antiplatelet therapies? Those are the sort of pieces that this study doesn't answer, but at least it gives us a flavor of what might be considered,” Dr. E. Magnus Ohman, director of the program for advanced coronary disease at Duke University, Durham, N.C., commented after the study was presented.
“The issue may be not prolonging the infusion, but rather focusing on the platelet activation component where we actually know from some scientific areas that this may be our best approach.”
Dr. Cortese and Dr. Ohman both said that the conclusions that can be drawn from the study are limited by its small sample size and the use of radial access sites in more than 83% of the patients. Access sites in the radial artery have a much lower rate of bleeding than do those in the femoral artery. Significant reductions in bleeding events from femoral access sites have been a major part of the advantage ascribed to bivalirudin in other studies.
Procedure-related MIs occurred significantly less often in patients who received prolonged bivalirudin. DR. CORTESE