フォンダパリヌクス使用中のPCI患者においては標準用量のヘパリンが最良である

FUTURA/OASIS 8:フォンダパリヌクスで治療されているACS患者に低用量の未分画ヘパリンを用いても出血または血管合併症は減少しない
FUTURA/OASIS 8: Low dose of unfractionated heparin in ACS patients treated with fondaparinux does not reduce bleeding or vascular complications
2010年European Society of Cardiology学会で発表されたFUTURA/OASIS 8の結果から、抗血栓薬フォンダパリヌクスで治療されているPCI患者に低用量のヘパリンを使用しても出血または血管合併症の発現率は減少しないことが示された。FUTURA/OASIS 8は不安定狭心症または心筋梗塞(MI)で入院し72時間以内にPCIを施行された患者2,026人を対象としたphase IIIの多施設無作為化トライアルである。患者は病院到着後できるだけ早く1日2.5mgのファオンダパリヌクスを投与され、PCIが必要な患者は低用量の固定用量のヘパリン(50U/kg)または標準用量のヘパリン(85U/kgまたはGP IIb/IIIa受容体阻害薬と併用する場合は60U/kg)を投与される群に無作為に割り付けられた。PCIに伴う重大な出血は低用量ヘパリン群で1.4%であり、標準用量群では1.2%であった。一次エンドポイント(PCIに伴う重大な出血または重大な血管合併症の合計)は両群間で差がなかった。しかし、低用量ヘパリン療法で重大な出血のリスクは低下しなかったものの、重大でない出血率は60%減少した。低用量ヘパリンにより死亡、MIまたは標的血管再血行再建術(二次エンドポイント)のリスクは高くなる傾向にあった。
Full Text

Results from the FUTURA/OASIS 8 study presented at the ESC Congress 2010 provide initial evidence that a low dose of unfractionated heparin does not reduce the incidence of bleeding or vascular complications in PCI patients treated with the anticoagulant fondaparinux. Findings showed that the rates of peri-PCI major bleeding were 1.4% in those given low dose heparin and 1.2% the standard dose.

"There has been a widely held view that lowering heparin dose also lowers bleeding rates during PCI," said principal investigator Dr. Sanjit Jolly, Assistant Professor of Medicine in the Michael G. DeGroote School of Medicine at McMaster University, "but randomized trial data have been lacking. Now, results from this study challenge that view."

An earlier trial, OASIS 5, also coordinated by McMaster University, had shown that anticoagulation with fondaparinux was more effective in reducing mortality and serious bleeding rates in post-MI patients than with enoxaparin. However, rates of catheter thrombosis during angioplasty with fondaparinux were found to be higher than with enoxaparin, which prompted the adjunctive use of unfractionated heparin to prevent clotting in patients treated with fondaparinux. "However," explained Dr. Jolly, "there was uncertainty about the optimal dose."

FUTURA/OASIS 8, designed to resolve that uncertainty, was a phase 3, multicentre, randomized trial in 2026 patients undergoing PCI within 72 hours of hospital admission for unstable angina or MI. As soon as possible after arrival, they received fondaparinux 2.5 mg daily, and those requiring PCI were randomized to low fixed dose heparin (50 U/kg) or standard dose heparin (85 U/kg or 60 U/kg with glycoprotein IIb/IIIa inhibitors).

The primary outcome was a composite of peri-PCI major bleeding, minor bleeding or major vascular complications, and results showed there was no difference between the two dose regimes in this endpoint. However, while the low dose regimen did not lower the risk of major bleeding, it did lower minor bleeding rates by 60%. And there was also a trend towards higher risk of death, MI or target vessel revascularization (secondary endpoint) with the lower dose. The rates of catheter thrombosis were very low in both groups (0.5% and 0.1% in the low and standard dose respectively).

It was also noted that the rates of major bleeding in FUTURA-OASIS 8 (1.4% low dose and 1.2% standard dose) were not significantly different from that observed in the fondaparinux arm of the OASIS 5 trial (1.5%) but lower than in the enoxaparin arm (3.6%).

"What these results imply," said Dr. Jolly, "is that the standard dose of unfractionated heparin may be the optimal treatment strategy in PCI patients on fondaparinux - while maintaining the major advantage of fondaparinux which is a low rate of major bleeding."