Stockholm, Sweden, 30 August: With both bleeding und thrombotic complications having a negative effect on PCI outcomes, increasing efforts have been made to improve PCI anticoagulation regimens. Although unfractionated heparin has been the standard anti-thrombotic agent in interventional cardiology for decades, there is still no solid evidence from large clinical trials to guide its dosing during PCI.
Two dosing regimens are currently recommended: an initial bolus dose of 70-100 U/kg bodyweight followed by additional boluses under ACT (activated clotting time) guidance; and a single bolus dose of 100 U/kg (more common in Europe). Recently, the direct thrombin inhibitor bivalirudin has emerged as an effective alternative treatment to heparin in patients undergoing PCI.
However, most randomised trials with bivalirudin have been in comparison to a combination of heparin and glycoprotein IIb/IIIa inhibitors. The first trial to compare bivalirudin with heparin alone in biomarker-negative patients undergoing contemporary PCI was the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3 trial in which a bolus dose of 140 U/kg unfractionated heparin was compared with bivalirudin. Although net clinical outcomes were comparable, there was an increased risk of bleeding with this heparin dose compared to bivalirudin.
Now, the prospective, multicentre, single-arm, open-label, historical control ISAR-REACT 3A trial has assessed the effect of a reduction in heparin dose (from 140 to 100 U/kg), which suggests, according to investigator Dr Stefanie Schulz from the Deutsches Herzzentrum, Munich, that in biomarker-negative patients "a reduced dose of heparin represents a simple and safe method of lowering the bleeding risk after PCI without increasing the risk of ischaemic complications".
The trial enrolled a total of 2505 patients in three centres in Germany. All patients received a reduced bolus dose of 100 U/kg heparin during PCI. At 30 days, the incidence of the primary net clinical outcome endpoint (a composite of ischaemic events [death, MI and urgent target vessel revascularisation] and bleeding) was significantly reduced in the lower heparin dose group compared to the historical heparin group of ISAR-REACT 3 (7.3% vs. 8.7%, P=0.045). This was achieved by a non-significant reduction in both ischaemic and bleeding components of the primary endpoint.
A second objective of the trial was a comparison of the lower heparin dose group with the historical bivalirudin group of ISAR-REACT 3. The lower heparin dose met the criterion of non-inferiority compared to bivalirudin, said Dr Schulz.