待機的PCIにおけるヘパリン用量は低い方が好ましい

The ISAR-REACT 3A trial：待機的PCI中のヘパリン用量を低下させることにより出血および血栓性の合併症が減少する
The ISAR-REACT 3A trial: Low heparin dose during elective PCI reduces bleeding and thrombotic complications
低用量ヘパリンはPCI後の虚血の合併症を増加させることなく出血リスクを低下させる簡便で安全な方法であると2010年European Society of Cardiology学会のホットラインセッションで発表され、European Heart Journalオンライン版に掲載された。この前向き多施設シングルアームオープンラベルのhistorical control ISAR-REACT 3A（冠動脈内ステントおよび抗血栓療法：冠動脈治療に対する迅速早期処置：Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment）トライアルは、ヘパリン用量を140U/kgから100に減量することの影響を評価した。トライアルには2,505人の患者が組み入れられ、全員がPCI中に低用量の100U/kgのボーラスのヘパリンを投与された。30日後の正味の一次臨床予後エンドポイント（虚血イベント[死亡、MIおよび緊急の標的血管血行再建術施行]の累計および出血）発現率は、ISAR-REACT 3の従来用量ヘパリン群と比較し、低用量ヘパリン群において有意に低かった（7.3%対8.7%、 P=0.045）。この結果は、一次エンドポイントの虚血および出血の要素が有意ではないが減少したことにより達成された。このトライアルのもう1つの目的は、低用量ヘパリン群とISAR-REACT 3の従来のbivalirudin群を比較することであった。低用量ヘパリンはbivalirudinと比較し非劣性のクライテリアに合致した。
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With both bleeding and thrombotic complications having a negative effect on PCI outcomes, increasing efforts have been made to improve PCI anticoagulation regimens. Although unfractionated heparin has been the standard anti-thrombotic agent in interventional cardiology for decades, there is still no solid evidence from large clinical trials to guide its dosing during PCI.

Two dosing regimens are currently recommended: an initial bolus dose of 70-100 U/kg bodyweight followed by additional boluses under ACT (activated clotting time) guidance; and a single bolus dose of 100 U/kg (more common in Europe). Recently, the direct thrombin inhibitor bivalirudin has emerged as an effective alternative treatment to heparin in patients undergoing PCI.

However, most randomized trials with bivalirudin have been in comparison to a combination of heparin and glycoprotein IIb/IIIa inhibitors. The first trial to compare bivalirudin with heparin alone in biomarker-negative patients undergoing contemporary PCI was the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3 trial in which a bolus dose of 140 U/kg unfractionated heparin was compared with bivalirudin. Although net clinical outcomes were comparable, there was an increased risk of bleeding with this heparin dose compared to bivalirudin.

Now, the prospective, multicentre, single-arm, open-label, historical control ISAR-REACT 3A trial has assessed the effect of a reduction in heparin dose (from 140 to 100 U/kg), which suggests, according to investigator Dr. Stefanie Schulz from the Deutsches Herzzentrum, Munich, that in biomarker-negative patients "a reduced dose of heparin represents a simple and safe method of lowering the bleeding risk after PCI without increasing the risk of ischemic complications".

The trial enrolled a total of 2505 patients in three centers in Germany. All patients received a reduced bolus dose of 100 U/kg heparin during PCI. At 30 days, the incidence of the primary net clinical outcome endpoint (a composite of ischemic events [death, MI and urgent target vessel revascularization] and bleeding) was significantly reduced in the lower heparin dose group compared to the historical heparin group of ISAR-REACT 3 (7.3% vs. 8.7%, P=0.045). This was achieved by a non-significant reduction in both ischemic and bleeding components of the primary endpoint.

A second objective of the trial was a comparison of the lower heparin dose group with the historical bivalirudin group of ISAR-REACT 3. The lower heparin dose met the criterion of non-inferiority compared to bivalirudin, said Dr. Schulz.

Researchers presented the ISAR-REACT 3A study results during a Hotline session at ESC Congress 2010. It was simultaneously published online in the European Heart Journal.