FUTURA/OASIS-8: Standaard-dosis heparine aanbevolen bij PCI
FUTURA/OASIS-8: Standard-dose heparin recommended during PCI to avoid catheter thrombosis with fondaparinuxAugust 31, 2010
Stockholm, Sweden - ACS patients undergoing PCI being treated with fondaparinux as the main anticoagulant should receive standard-dose unfractionated heparin during the procedure to avoid catheter thromboses, according to the conclusions drawn from the FUTURA/OASIS-8 trial.
Results of the trial, presented at the European Society of Cardiology (ESC) 2010 Congress today and published online in the Journal of the American Medical Association, showed no major advantages of low-dose heparin over standard-dose heparin in such patients, and neither dose increased major bleeding when compared with the historical control group of fondaparinux alone in the OASIS-5 trial.
Speaking at an ESC press conference, co-lead investigator of the FUTURA/OASIS 8 trial, Dr Sanjit Jolly (McMaster University, Hamilton, ON) said: "The trial has resolved this important issue with fondaparinux. It has shown that we can reduce the problem of catheter thrombosis without increasing major bleeding. This means that ACS patients on fondaparinux can undergo PCI safely with adjunctive [intravenous] IV heparin."
The FUTURA/OASIS-8 trial was conducted to deal with the issue of catheter thrombosis, which has been associated with the use of fondaparinux alone in ACS patients undergoing PCI and has limited the widespread adoption of the drug in this setting. In the large-scale OASIS-5 trial in ACS patients, fondaparinux was shown to be preferable to enoxaparin, halving major bleeding rates, which was associated with a mortality reduction at 30 days. However, the one downside of fondaparinux in this trial was the excess of catheter thrombosis seen in patients undergoing PCI (0.9% vs 0.4% with enoxaparin).
The OASIS investigators thus proposed that patients undergoing PCI on fondaparinux should receive additional anticoagulation with unfractionated heparin during the procedure. This recommendation was based on an analysis of 306 patients from OASIS-5 and OASIS-6 (another trial of fondaparinux, but this time in STEMI patients) who had received open-label unfractionated heparin while on fondaparinux and experienced a low rate of catheter thrombosis (0.3%). However, this was based on only a small number of patients, and there was uncertainty over the optimum dose.
To look into this issue further, the OASIS investigators conducted the FUTURA/OASIS-8 study, in which 2026 patients undergoing PCI within 72 hours of ACS initially treated with fondaparinux received either low-dose unfractionated heparin (50 U/kg, regardless of use of GP IIb/IIIa blocker use) or standard-dose unfractionated heparin (85 U/kg or 60 U/kg with GP IIb-IIIa inhibitors), adjusted by activated clotting time (ACT).
Results showed that the low fixed-dose of heparin was not superior to standard ACT-guided heparin in terms of preventing peri-PCI major bleeding or major vascular access-site complications. Thrombotic events were not significantly different between the treatment groups. Catheter thrombosis was said to be "rare"—five cases (0.5%)—in the low-dose heparin group and "very rare"—one case (0.1 %)—in the standard-dose heparin group.
Cochair of the hot-line session at which the trial was presented, Dr Ralph Brindis (Kaiser Permanente, San Francisco, CA), president of the American College of Cardiology, said he thought this study could have an important impact on care. "Despite the incredible benefits of fondaparinux shown in OASIS-5, the uptake of this agent has been slow, especially in the US, where ACS patients are generally taken to the cath lab quickly. Interventionalists tend to like to measure ACT levels during the PCI procedure in the lab. They are wary of using agents such as fondaparinux and enoxaparin, which are not titratable in the same way as unfractionated heparin. Now that they can see that it is safe to give unfractionated heparin in the lab to patients who have already been started on fondaparinux, this could lead to a paradigm change," he commented.
Jolly explained that because the SYNERGY trial showed a bleeding hazard when switching to or adding unfractionated heparin in patients already given enoxaparin, this has led to concerns that a similar increased bleeding rate may occur if heparin is added to fondaparinux. "But we have now shown that this was not the case. We must learn that one agent is different from another. Fondaparinux behaves very differently in this regard to enoxaparin. Our results are very different from those of SYNERGY," he told.
Unfractionated heparin alone still best for high-risk patients?
Commenting on how to incorporate these latest results into clinical practice, designated discussant of the study at the hot-line session, Dr Dariusz Dudek (Institute of Cardiology, Krakow, Poland), pointed out that high-risk non-ST-elevation ACS patients are normally referred for immediate angiography and that in this population, which was excluded from the FUTURA/OASIS-8 trial, standard unfractionated heparin is probably still the best anticoagulant to choose, as it is "sufficient and simpler."
But fondaparinux would be a reasonable choice for lower-risk ACS patients in whom angiography can be postponed or is not considered, he added. Then, if these patients are later referred to angiography, unfractionated heparin should be added in the cath lab.He noted that low-dose heparin in FUTURA/OASIS-8 was associated with an "obvious trend" toward a higher rate of ischemic complications but did not appear to reduce major bleeding, so it was important to make sure that higher doses of heparin were used in this setting.