FUTURA OASIS 8: A randomised trial comparing two regimens of adjunctive intravenous unfractionated heparin during PCI in high-risk patients with non-STE-ACS treated with fondaparinux
Acute Coronary Syndromes (ACS)
Session number: 708011 - 708012
Session title: Hot Line III - Cardiovascular disease and rhythm disturbances
Authors: Jolly, Sanjit - Dudek, Dariusz
List of Authors:
STEG, Philippe Gabriel; JOLLY, Sanjit; MEHTA, Shamir; YUSUF, Salim
The optimal unfractionated heparin (UFH) regimen for percutaneous coronary intervention (PCI) in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) patients treated with fondaparinux, is uncertain Objective: Compare the safety of two UFH regimens during PCI in high-risk patients with NSTE-ACS initially treated with fondaparinux.
Design setting and participants:
Double-blind randomized parallel-group trial in 179 hospitals in 18 countries of 2026 patients undergoing PCI within 72 h, nested within a cohort of 3235 high-risk patients with NSTE-ACS initially treated with fondaparinux enrolled from February 2009 to March 2010.
Low dose UFH: 50 U/kg iv regardless of use of GpIIb/IIIa inhibitors. Standard dose UFH: 85 U/kg (60 U/kg with GpIIb/IIIa inhibitors) adjusted by blinded activated clotting time (ACT) Main Outcome Measures: Composite of major bleeding, minor bleeding or major vascular access site complications up to 48 h post-PCI.
Key secondary outcome:
composite of major bleeding at 48 h with death/MI/Target vessel revascularization (TVR) at day 30
The primary outcome occurred in 4.7% vs. 5.8% of the low and standard dose groups’ patients respectively (OR: 0.80, 95%CI 0.54-1.19, p=0.27). The rates of major bleeding were not different but the rates of minor bleeding were lower with low vs. standard dose regimen (0.7% vs. 1.7%, OR: 0.40, 95%CI 0.16-0.97, p=0.04). For the key secondary outcome, the rates for low vs. standard dose regimen were 5.8% vs. 3.9% (OR: 1.51; 95%CI 1.00-2.28, p=0.05) and for death/MI/TVR 4.5% vs. 2.9% (OR: 1.58, 95%CI 0.98-2.53, p=0.06). Catheter thrombus rates were very low (0.5 and 0.1% in the low and standard dose groups respectively, p=0.15)
Low compared to standard dose UFH did not reduce major peri-PCI bleeding and vascular access site complications. Catheter thromboses are rare in NSTE-ACS patients treated with fondaparinux when UFH is added during PCI.
The results from the FUTURA/OASIS 8 study were presented today at the HOTLINE III session by Dr Sanjit Jolly. The primary study objective was to evaluate the safety of 2 dose regimens of adjunctive i.v. UFH (low or standard dose) during PCI in high risk UA/NSTEMI patients initially treated with s.c. fondaparinux and referred for early angiography. There were 2026 high risk NSTEACS patients randomized in this study. No differences were observed for the primary study outcome of peri-PCI major, minor bleeds and vascular access complications (standard dose vs low dose UFH: 5.8% vs 4.7%). Moreover, peri-PCI major bleedings were also similar in both groups despite significantly lower UFH dose in “low dose” group (1.2% vs 1.4%). However, when looking at the combined endpoint of death, reMI and TVR there seems to be a very strong trend towards more ischaemic adverse events in low-dose group on the verge of statistical significance (2.9% vs 4.5%, p=0.058).
Although the FUTURA study group was considered as high risk (>60 y, >25% DM, ca. 80% troponin positive) the median time from chest pain onset to PCI exceeded 24 hours as recommended by ACC/AHA and ESC guidelines .
The results of the FUTURA/OASIS 8 trial indicate that NSTE ACS patients should receive ACT guided standard full dose of UFH in order to maintain proper anticoagulation even if pretreated with fondaparinux with no difference in bleeding complications and very obvious trend in reduction of ischaemic ones. The diference in MACE rate (death, reMI, TVR) was mainly driven by stent thrombosis and TVR, which could raise the question of proper anticoagulation in the low-dose group
Based on the FUTURA results, it seems that pretreatment with fondparinux is still not sufficient to allow to reduce the UFH dose for patients undergoing PCI. However, fondaparinux may still be used in non-high risk patients in whom immediate/early angiography may be postponed or not considered.
The content of this article reflects the personal opinion of the
author/s and is not necessarily the official position of the
European Society of Cardiology.