STOCKHOLM – A single bolus dose of 100 U/kg of unfractionated heparin in patients who undergo elective percutaneous coronary intervention is superior to the long-standard 140-U/kg regimen, according to a large prospective study.
Photo credit: European Society of Cardiology
Dr. Stefanie Schulz presents the findings of the ISAR-REACT 3A trial.
“This reduced dose of heparin represents a simple and safe method of lowering the bleeding risk after PCI without increasing the risk of ischemic complications,” Dr. Stefanie Schulz concluded in presenting the findings of the ISAR-REACT 3A (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) trial at the annual congress of the European Society of Cardiology.
ISAR-REACT 3A was a single-center study that included 2,505 cardiac biomarker–negative patients who underwent elective PCI after being premedicated with clopidogrel. All patients received a single bolus of unfractionated heparin (UFH) at 100 U/kg
The study featured two control arms, both comprising historical controls that were obtained from the previously published ISAR-REACT 3 trial (N. Engl. J. Med. 2008;359:688-96). One control group consisted of 2,281 patients randomized to a single 140-U/kg bolus of UFH, the regimen that was followed in elective PCI for decades by many interventional cardiologists. The other comparison group was made up of 2,289 patients randomized to bivalirudin in the same trial.
The ISAR-REACT 3A study was carried out because in the earlier ISAR-REACT 3, the 140-U/kg dose of UFH proved to be comparable with bivalirudin in terms of net clinical outcome, but was associated with a significantly greater bleeding rate. The main hypothesis tested in ISAR-REACT 3A was that a lower dose of heparin would be as effective as 140 U/kg in preventing ischemic events, and would have less bleeding.
This proved to be the case. The primary study quadruple end point – the 30-day combined rate of death, MI, urgent target vessel revascularization, and in-hospital major bleeding – occurred in 7.3% of the lower-dose UFH group, compared with 8.7% of those on 140 U/kg. The resultant highly significant 25% relative risk reduction that emerged from a multivariate propensity analysis was driven largely by the reduced risk of major bleeding in the 100-U/kg UFH group (3.6% vs 4.6%), reported Dr. Schulz of the German Heart Center at the Technical University of Munich.
The comparison between the lower-dose UFH and the bivalirudin study arms was designed as a noninferiority analysis. The 30-day, combined end point occurred in 7.3% of the UFH group and 8.3% of those on bivalirudin, indicating that the net clinical outcome with 100 U/kg of UFH was noninferior to the direct thrombin inhibitor. The major bleeding rate was 3.6% with UFH and 3.1% with bivalirudin.
Discussant Dr. Christian Hamm hailed ISAR-REACT 3A as “an important contribution to interventional cardiology” because the use of UFH has for decades been guided mainly by expert opinion, with very little in the way of randomized, controlled data.
He wished, however, that the Munich researchers had tested an even lower dose of UFH – say, 70 U/kg.
“I think it’s reasonable to even further reduce our anticoagulation in elective PCI because we have fewer thrombogenic guidewires and other materials today, we have shorter procedures because the materials are better, we have less thrombogenic contrast media, and we have in most patients premedication with clopidogrel. So in my view, the take-home message from ISAR-REACT 3A is that in elective PCI, don’t use more than 100 U/kg of UFH; you probably can use even less,” declared Dr. Hamm of the Kerckhoff Clinic, Bad Nauheim, Germany.
Disclosures: Dr. Schulz and Dr. Hamm declared having no financial conflicts.