The study is being released early online to coincide with its presentation at the European Society of Cardiology meeting in Stockholm.
Previous study results suggested the use of unfractionated heparin as supplemental therapy at the time of percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries) for patients with non-ST segment elevation (a certain pattern on an electrocardiogram) acute coronary syndromes (such as heart attack or unstable angina) who were treated with fondaparinux and undergoing PCI. But there is disagreement on the appropriate range of dosing of heparin during PCI for these patients, according to background information in the article. "The optimal dosing of unfractionated heparin should maintain the safety profile of fondaparinux but achieve adequate antithrombin effect to prevent catheter thrombus [blood clots]," the authors write.
Sanjit S. Jolly, M.D., of Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada, and colleagues with the Fondaparinux Trial With Unfractionated Heparin During Revascularization in Acute Coronary Syndromes (FUTURA)/OASIS-8 trial evaluated the safety of two dose regimens of adjunctive intravenous unfractionated heparin during PCI in high-risk patients. The randomized trial included 179 hospitals in 18 countries and involved 2,026 patients undergoing PCI within 72 hours, who were from a group of 3,235 high-risk patients with non-ST segment elevation acute coronary syndromes initially treated with fondaparinux, enrolled from February 2009 to March 2010. Patients received intravenously either low-dose unfractionated heparin (50 U/kg, regardless of use of glycoprotein IIb-IIIa [GpIIb-IIIa] inhibitors) or standard-dose unfractionated heparin (85 U/kg [60 U/kg with GpIIb-IIIa inhibitors]), adjusted by activated clotting time (ACT).
The researchers found that the primary composite outcome (major bleeding, minor bleeding, or major vascular access site complications up to 48 hours after PCI) occurred in 4.7 percent of the patients in the low-dose group and 5.8 percent in the standard-dose group. There was a nonsignificant increase in the key secondary outcome (peri-PCI major bleeding [near the time of the PCI procedure], death, heart attack, and target revascularization at 30 days), 5.8 percent in the low-dose group vs. 3.9 percent in the standard-dose group. Peri-PCI minor bleeding was lower in the low-dose group vs. the standard-dose group (0.7 percent vs. 1.7 percent).
"The major bleeding events up to 30 days were similar between the low- and standard-dose groups (2.2 percent vs. 1.8 percent)," the researchers write. "The secondary outcome of death, heart attack, or target vessel revascularization was similar, although nominally higher, in patients receiving low-dose vs. standard-dose unfractionated heparin (4.5 percent vs. 2.9 percent)."
Thrombotic events were not significantly different between the treatment groups, with catheter thrombosis seen in 5 cases (0.5 percent) in the low-dose group and 1 case (0.1 percent) in the standard-dose groups.
The authors note that the major finding of this study is that low fixed-dose heparin is not superior to standard ACT-guided heparin dosing (after the use of fondaparinux) in terms of preventing peri-PCI major bleeding or major vascular access site complications.
"The finding that adding ACT-guided unfractionated heparin to fondaparinux while treating patients with acute coronary syndromes does not increase major bleeding is important in the context of modern PCI practice. Reducing bleeding is potentially important because several studies have suggested that moderate reductions in bleeding may lead to a reduction in longer term ischemic events, particularly mortality. In our study, there was no clinical benefit to using the experimental low-dose regimen, except for a reduction in minor bleeding alone (but not in the combination of major and minor bleeding)," the authors write. "These findings support using the currently recommended standard ACT-guided dose of unfractionated heparin when performing PCI in patients with non-ST segment elevation acute coronary syndromes who are treated with fondaparinux."