Novel LMWH noninferior to UFH for PCI patients
MedWire News: A novel low molecular weight heparin (LMWH) offers at least comparable efficacy to unfractionated heparin (UFH) for patients undergoing percutaneous coronary intervention (PCI), suggest results from the EMINENCE trial.
The Evaluation of M118 IN pErcutaNeous Coronary intErvention (EMINENCE) trial compared the ability of M118 and UFH to prevent a composite 30-day outcome of death, stroke, myocardial infarction (MI), repeat revascularization, thrombocytopenia, catheter thrombus, bailout use of glycoprotein IIb/IIIa inhibitors, and bleeding in 503 North American patients undergoing elective PCI.
“This phase II randomized trial demonstrates that M118 is well tolerated and feasible to use as an anticoagulant in patients undergoing elective PCI and forms the basis for further investigation of this agent in ischemic heart disease,” say Sunil Rao (Duke Clinical Research Institute, Durham, North Carolina, USA) and co-authors.
M118 is a novel LMWH that is active against factors (F)Xa and IIa, and has predictable pharmacokinetics after intravenous (iv) and subcutaneous administration, the team explains.
In addition, the structure of M118 means that unlike other LMWHs, its effects are reversible to subtherapeutic levels with protamine sulfate, and that patients can be monitored using standard anticoagulation assays, allowing point-of-care tests.
The patients were randomly assigned to open-label treatment with iv UFH 70 U/kg or iv M118 at a dose of 50, 75 or 100 IU/kg.
The primary composite endpoint was reached by 31.1% of UFH-treated patients versus 22.7%, 28.3%, and 30.1% of patients given M118 at 50, 75, and 100 IU/kg, respectively.
Analysis of pooled results for M118 doses showed that the novel LMWH was noninferior to UFH for the prevention of PCI-related complications, at rates of 28.4% and 31.1%, respectively.
The combined rate of 24-hour major and minor bleeding was slightly higher in M118- than UFH-treated patients (18.8% vs 17.2%), and this was attributed to an increased rate of minor bleeding in M118 patients. No significant difference was found in major bleeding between the groups.
In addition, M118 and UFH had comparable rates of any (75.6% vs 76.8%) and severe (9.9% vs 13.2%) adverse events.
Rao et al note that the EMINENCE trial was conducted in low-risk patients without use of other agents.
“The safety and efficacy of M118 for the treatment of higher-risk patients and in combination with glycoprotein IIb/IIa and other emerging antiplatelet agents will need to be evaluated in adequately powered phase III trials,” they conclude.
“Similarly, direct comparisons of M118 to other anticoagulants such as enoxaparin and bivalirudin will need to be explored in the future.”
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By Lynda Williams